Research Collection
Doctoral Thesis
Mechanism-Based Development of Carbopalladation Reactions
Author(s): Tchawou Wandji, Augustin Armand Senghor
Publication Date: 2016
Permanent Link: https://doi.org/10.3929/ethz-a-010796723
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ETH Library DISS. ETH NO. 23870
Mechanism-Based Development of Carbopalladation Reactions
A thesis submitted to attain the degree of
DOCTOR OF SCIENCES of ETH ZURICH
(Dr. sc. ETH Zurich)
presented by
AUGUSTIN ARMAND SENGHOR TCHAWOU WANDJI
M.Sc. ETH, Ecole Polytechnique Fédérale de Lausanne, Switzerland
born on 23.11.1984
citizen of Cameroon
Accepted on the recommendation of
Prof. Dr. Peter Chen, examiner
Prof. Dr. Antonio Mezzetti, co-examiner
2016
“Here we are – despite the delays, the confusion, and the shadows en route – at last, or for the moment, where we always intended to be.” ― Julia Glass, Three Junes
Dedication
This thesis is dedicated to the loving memory of my father. Thank you for having sacrificed so much for my education, regardless of the circumstances. From where you are right now, I hope I have made you proud.
Acknowledgements
First and foremost, I wish to thank my supervisor, Prof. Dr. Peter Chen, for this enormous opportunity he gave me to pursue my studies in his group at ETH Zurich. Since the first day I started my doctoral studies, I have always been impressed and inspired by his calm, his passion and immense knowledge for a wide range of subjects besides chemistry. Peter, I am deeply grateful for your patience, the trust you put in me, and for believing in me even when I gave you no reason to do so, allowing me all the freedom to explore my ideas while providing me with your guidance and enthusiastic support.
I am also grateful to Prof. Dr. Antonio Mezzetti for kindly accepting to act as co-examiner to my thesis.
Many thanks to PD Dr. Andreas Bach for his tremendous effort in the management of the group throughout these past years, and for fixing the issues one would have encountered with the cluster.
Armin Limacher is greatly thanked for his availability, willingness, and promptness to help with all the technical work. I will always remember our experience with the phosphine gas.
I would like to thank all the former and present labmates: Dr. Sebastien Torker, Dr. Juan
Sarria Toro, Dr. Eva Zocher, Dr. David Ringger, Dr. Krista Vikse, Dr. Tim den Hartog,
Yanan Miao, and Stefan Künzi for welcoming me in the lab G218, for all the discussion and for making the lab a friendly and pleasant place to work.
Many thanks and praise also go to all the other past and present colleagues: Dr. Mihai
Raducan, Dr. Erick Couzijn, Dr. Ilia Kobylianskii, Dr. Marija Jovic, Dr. Daniel Serra, iv | Dedication and Acknowledgements
Dr. Deborah Mathis, Dr. Laurent Batiste, Dr. Adil Zhugralin, Dr. Yu-Ying Lai, Inesa
Semic, Dr. Renana Poranne, Dr. Alexandra Tsybizova, Dr. Larisa Miloglyadova, Raphaël
Oeschger, Stefan Jungen, Joël Gubler, Robert Pollice, Marek Bot, and Lukas Fritsche for
creating such a positive and stimulating atmosphere in the group. You all helped me in
different ways, scientifically and personally, and I enjoyed the time spent together in and
outside ETH.
I want to thank Mirella Rutz and Anke Witten for their excellent administrative work, which allowed us to focus more on our chemistry.
I further want to thank the NMR-team: Dr. Marc-Olivier Ebert, Rainer Frankenstein, René
Arnold, and Stephan Burkhardt for the measurements of my samples, and their kindness, allowing me to always have a machine available for my work at their service.
The team at the X-ray service (Dr. Bernd Schweizer, Dr Nils Trapp, and Michael Solar) is also greatly acknowledged for kindly measuring and solving all my X-ray structures.
Many thanks also go to the MS service led by Dr. Xianyang Zhang for the measurement of all the HRMS, to the service for microelemental analysis at the LOC, and to Dr. Thomas-
Bruno Schweizer for his help with the GPC measurements.
I also appreciated the cheerful atmosphere at the HCI-shop. Thank you for your assistance.
Special thanks go to Elsy Mankah, Dr. Nana Diarra and “my little sister from Zürich” Djata
Sigam, friends I met during my studies at ETH. I will always remember all the discussions,
laughs and fun experiences we shared.
It is with an inexpressible gratitude that I would like to thank my entire family, especially
my mother (Yvonne), my brothers (Aymerich, Batista, Donald, and Gaëtan) and sisters
(Charline, Laurine, Syntych, and Daphenel), and my grand-mother (Mama Meta) for their
prayers and good wishes, endless encouragement and support despite the distance. To my
brother Batista Tchawou, I am glad to know that I can trust you and have your sincere
opinion whenever it is needed. This helped me a lot during these last years. Thank you.
I have to thank my great friend and brother, François Ekane, for his advices, endless
support and motivation. He has always been there for me through all my ups and downs. Dedication and Acknowledgements | v
I would like to express my recognition to my parents-in-law (Volker and Nike-Sabine), and
to my sister-in-law (Pia-Alina) for welcoming me as a family member and for their support
and care.
To my lovely wife, my friend, my first and wonderful supporter, Nina-Luisa, every day that
goes by makes me realize how lucky and blessed I am to have you in my life. Thank you for
everything you have done and continue to do for me.
Finally, I have the greatest respect and appreciation for other friends who, through different
experiences, have also contributed in making these PhD years possible: Andrea, Daniel,
Florian, Sophie, Ingo, Frieda, Alice, Ugo, Takuya, Guyleine, Alan, Daniela, Sierk, Amaia,
Santiago, and some others I probably forgot. Thank you all.
Table of Contents
Acknowledgments iii
Table of Contents vii
Abstract ix
Résumé xi
1. Introduction 1
2. Phosphine Sulfonate Pd-Based Catalysts: From the Deactivation to 21 the Regeneration in Situ
3. Mechanistic Investigations of a Novel Pd-Catalyzed Electrophilic 53 Cyclopropanation of Norbornene
4. Pd-Catalyzed Electrophilic Cyclopropanation of Electron-rich 75 Alkenes and Allylic Alcohols
5. Conclusions and Outlook 109
6. Experimental 113
Appendix A: Annexes 153
Appendix B: List of Publications and Presentations 171
Appendix C: Curriculum Vitae 173
Abstract
The growing interest for alternative routes to the radical and anionic methods used in the preparation of functionalized polymeric materials with a high degree of control over their physical and chemical properties for specialty applications, has led to the development of promising palladium-based systems that are capable of producing polymers with a promising ratio of the incorporation of polar monomers such as methyl acrylate, in both branched and linear fashion and in high molecular weight. The ability of the active but short-lived palladium catalysts, stabilized by the phosphine sulfonate ligands, to connect a non-negligible number of consecutive units of methyl acrylate motivated the studies presented in the first part of this thesis. The understanding of the catalyst’s main deactivation pathway and the identification of relevant palladium intermediates show the feasibility of an in situ regeneration of the catalysts from a highly reactive anionic palladium(0) intermediate, which is formed after β-hydride elimination followed by P–H or
O–H reductive elimination, and finally deprotonation. In an attempt to limit the constant occurrence of the β-hydride elimination, we prepared a series of phosphine sulfonate ligands that allowed a better incorporation of consecutive units of methyl acrylate in comparison to the original phosphine sulfonate ligand. The difficulties encountered in reproducing the quantitative reported polymerization results via carbopalladation do not allow us to apply our findings, but nevertheless leave a window open for future improvements in this field.
The carbopalladation reaction of norbornene to produce the corresponding cyclopropane using some iodomethyl boron compounds, either the trifluoroborate or a boronic ester, was recently developed based on a designed and novel mechanistic model called “diverted Heck”.
In the second part of this thesis, the proposed intermediates in the “diverted Heck” mechanism are observed by means of spectroscopic studies, and by isolation and X-ray crystallographic characterization. The experimental findings and the non-observed palladacyclobutane intermediate postulated in the “diverted Heck” mechanism are validated by DFT calculations in the gas phase. These findings together with reaction kinetics, point x | Abstract
to a separation of rate-determining and product-determining steps, and a mechanism-based
optimization of the yield, selectivity, and scope of the catalytic electrophilic
cyclopropanation of various electron-rich olefins and unprotected allylic alcohols. The
cyclopropanation reaction with crystalline, air-stable, non-hygroscopic and non-toxic reagents provides an alternative to Simmons-Smith-type reactions, as well as cyclopropanation procedures that require the use of diazomethane.
Résumé
L’intérêt grandissant pour des voies alternatives aux méthodes radicalaire et anionique utilisées dans la préparation de matériaux polymères fonctionnalisés avec un degré élevé de contrôle sur leurs propriétés physiques et chimiques, et ce pour des applications spécialisées, a conduit au développement de systèmes prometteurs à base de palladium capables de produire des polymères dotés d’un encourageant rapport d’incorporation de monomères polaires, tels que les acrylates de méthyle, à la fois de manière ramifiée et linéaire, et de poids moléculaire élevé. La capacité des catalyseurs actifs de palladium stabilisés par des ligands phosphines sulfonates, de courte durée de vie, à connecter un nombre non négligeable d'unités d'acrylates de méthyle consécutives, a motivé les études présentées dans la première partie de cette thèse. La compréhension de la voie de désactivation principale du catalyseur et l'identification des intermédiaires de palladium clés montrent la faisabilité d'une régénération in situ des catalyseurs à partir d’un intermédiaire anionique et très réactif de palladium (0) formé à la suite d’une β-élimination d’hydrure de palladium suivie d’une élimination réductrice de type P–H ou O–H, et enfin d’une déprotonation. Dans une tentative permettant de limiter la constante survenance des β-éliminations d’hydrure de palladium, nous avons synthétisé une série de ligands de phosphines sulfonates qui permettent une meilleure incorporation d'unités consécutives d'acrylates de méthyle par rapport au ligand original. Les difficultés rencontrées dans la reproduction des résultats quantitatifs de polymérisation précédemment publiés via une réaction de carbopalladation ne nous permettent pas d'appliquer les résultats de nos recherches, mais néanmoins laissent une fenêtre ouverte en vue d’amélioration future dans ce domaine.
La réaction de carbopalladation de norbornène permettant de produire le cyclopropane correspondant en utilisant des composés iodométhylés de bore, que ce soit des composés de bore trifluorés ou d’esters boroniques, a été récemment développée sur la base d'un nouveau modèle mécanistique nommé "Heck détourné". Dans la seconde partie de cette thèse, les intermédiaires proposés dans le mécanisme de "Heck détourné" sont observés à l’aide xii | Résumé
d’études spectroscopiques, et par l’isolation et la caractérisation cristallographique par
rayons X. Les résultats expérimentaux obtenus, de même que l’existence de l’intermédiaire
palladacyclobutane non-observé mais postulé dans le mécanisme de "Heck détourné" sont validés par des calculs DFT en phase gazeuse. Ces résultats couplés à la cinétique de réaction pointent vers une séparation entre l’étape cinétiquement déterminante et l’étape déterminante de formation du produit, et vers une optimisation du rendement de la réaction, de la sélectivité et la portée de la réaction de cyclopropanation catalytique de diverses oléfines riches en électrons et alcools allyliques non protégés basées sur le mécanisme de la réaction. Cette réaction de cyclopropanation qui utilise des réactifs cristallins, stables à l'air, non hygroscopiques et non toxiques offre une alternative aux réactions de la famille Simmons-Smith, ainsi qu’aux procédures de cyclopropanation qui nécessitent l'utilisation du diazométhane.
Chapter 1
Introduction
1.1. Palladium – History and Properties
The 46th element of the periodic table, palladium, is a metal of the family of the late transition metals. It was through an anonymous handbill distributed in London in April 1803 that
William Hyde Wollaston first disclosed the discovery and isolation of “Palladium; or, New
Silver”. The “New Noble Metal” was then offered for sale only at a shop in Gerrard Street,
Soho, London.1 Such an advertisement already represented at that time an unusual path to disclose the discovery of a new element. It was however not until July 4, 1805, in a paper read at the Royal Society, that Wollaston officially presented himself to the public as the one who discovered and isolated that element named after (2) Pallas, the second asteroid to be discovered a year prior. Unfortunately for Wollaston, due to the lack of a useful application of his discovery, 97% of his stock of palladium remained unsold by the time of his death in
1828.2
Palladium is part of the group 10 (Ni, Pd, Pt) transition metals and possesses a moderately large atomic radius, smaller than platinum but larger than nickel. More than a century after its original discovery, palladium was first applied in reactions such as oxidations, reductions, and hydrogenations of double and triple bonds – chemistry that had traditionally been performed with Ni and Pt. This established the affinity of the metal for these unsaturated 2 | Chapter 1
hydrocarbons, leading to the invention of the Wacker process in 1959 and its subsequent developments.3
Palladium is a rather soft and electronegative metal which can have a number of different
oxidation states but mostly favors the 0 (d10) and +2 (d8) oxidation states. The relative facile
interconversion between the palladium d10 and d8 and their accessible HOMO and LUMO
orbitals lead to the high propensity for concerted processes one would observe in palladium
catalysis.3 Pd is less prone to radical processes compared with Ni and is kinetically more
active than Pt. Its softness and electronegativity make it less oxophilic and more functional-
group-tolerant relative to other hard metals like Li or Mg. For example, it would exhibit a
high affinity toward soft π- and n-donors like the highly polarizable π-electron pair of a C=C
double bond. The high cost of palladium compared to many other metals has forced chemists
to develop catalytic reactions exhibiting high turnover numbers (TONs) and selectivities.4
1.2. Catalytic Intermolecular Carbopalladations
Since its discovery, palladium has emerged as one of the most versatile and useful metals in
organic synthesis, especially for the formation of carbon-carbon or carbon-heteroatom bonds.
Figure 1.1. Examples of cross-coupling applications in the drug industry.
Top-selling drugs like Crestor, Lapatinib, Gleevec, Naratriptan, Diovan, or Lipitor as well as
other pharmaceuticals, agrochemicals, and polymers use as key step in their synthesis at least
one of the palladium-catalyzed cross-coupling reaction, namely Mizoroki-Heck,5 Stille,6 Introduction | 3
Suzuki-Miyaura,7 Negishi,8 Sonogashira,9 Hartwig-Buchwald10, etc.
Scheme 1.1. Most important palladium-catalyzed C-C cross-coupling reactions.
Among all these reactions, the two most commonly applied in the last decades2 are the Suzuki-
Miyaura (often simplified as Suzuki) and the Mizoroki-Heck (sometimes simply called Heck)
reactions. Both Pd-catalyzed reactions require the presence of an organohalide (or
organopseudo-halide) as electrophile. An organoboron reagent will act as the nucleophile in
the Suzuki-Miyaura coupling, whereas an alkene plays that role in the case of the Mizoroki-
Heck reaction. It is the only type of cross-coupling transformation in which carbon-carbon
bonds are formed via carbopalladation of alkenes followed by a β-dehydropalladation step.
Although it is not the first reported catalytic reaction involving a carbopalladation step,3 the development of the Heck reaction resulted in an extensive use of palladium catalysts for the development of other Heck-type carbopalladation and other useful carbopalladation reactions, such as the coordination-insertion (co)polymerization11 and the cyclopropanation reaction
using diazomethane.12 4 | Chapter 1
1.2.1. Heck-type Carbopalladation Reactions
The first catalytic Pd-mediated C-C cross-coupling reactions, mostly known today as “Heck
coupling”, was developed in the 1970s.5a It then featured the coupling of an organic halide
(aryl iodides, vinyl bromide and benzyl chloride) as electrophilic partners with various alkenes
as the nucleophilic partners (ethylene, styrenes, methyl acrylate (MA)) at elevated
temperatures (≥ 100 °C), in the presence of a base and catalyzed by zero-valent Pd, or
generated in situ from a divalent Pd source. A few years later, Matsuda and co-workers
successfully investigated the same reaction using aryl diazonium salt as electrophiles.13 The general mechanistic scheme for these reactions is depicted in Scheme 1.1 and consist of four principal steps: oxidative addition of the electrophile, carbopalladation (coordination- insertion) of the olefin followed by the β-hydride elimination and the base-assisted reductive elimination steps.
1.2.1.1. Oxidative Addition
The oxidative addition of an organic halide/pseudohalide (R–X) to zero-valent Pd – usually the catalytically active 12-electron intermediate LPd(0) where L is a ligand – to generate a divalent R–Pd(Ar)(X) intermediate is the first step in many Heck-type reactions and other cross-coupling reactions. The exact mechanism of this elementary step, which is still under debate, depends on the nature of the organic electrophile involved. Although a single electron transfer (SET) from the Pd(0) metal to the electrophile has been proposed to take place in some cases, concerted processes are thought to be the preferred pathway for this transformation. Concerted two-electron processes may involve a nucleophilic displacement of the halide by attack of the metal at the carbon center (SN2-like) followed by the addition of
the anion X–, or an insertion of highly reactive Pd(0) species into the R–X bond (three center
cis-addition), resulting in different stereochemical palladium products, at least in principle.14
Subsequent isomerization to a more stable and different stereoisomer usually takes place.
Experimental studies on the oxidative addition showed that the oxidative addition of alkyl
C–X bonds to a metal center is more difficult than that of aryl and alkenyl C–X bonds.15 Introduction | 5
This is conventionally explained by the fact that C(sp3)–X bond in the alkyl electrophile is
more electron-rich than the C(sp2)–X bond in aryl and alkenyl electrophiles. The more
electron-rich the C–X bond, the more difficult the oxidative addition to the zero-valent Pd
metal. Computational studies16 suggest that the better reactivity of aryl versus alkyl halides
is related to the availability of π* orbitals in the C(sp2)–X bond that one cannot find in the
C(sp3)–X bond. Therefore, aliphatic C–X electrophiles are expected to be prone to adopt
preferentially a SN2-type transition state for oxidative addition while the three-center transition state will be followed by aryl and alkenyl C–X electrophiles.
Steric factors would dominantly determine the reactivity of alkyl C–X bonds toward the nucleophilic substitution i.e., methyl > ethyl > isopropyl > tert-butyl.17 On the
halide/pseudohalide series, the order of reactivity often follows the bond dissociation energy
of the C–X bond: C–I > C–Br = C–OTf > C–Cl. However, with monodentate ligands, the
oxidative addition of C–X electrophiles on the Pd(0) metal leads to the formation of a stable
dimer (usually as a Pd reservoir, Scheme 1.2) outside the catalytic cycle, which is in
equilibrium with the reactive monomeric oxidative addition species.18 Organoiodide
electrophiles have a higher propensity of forming the dimer than the bromide and chloride
equivalent.19
Scheme 1.2. The formation of a stable dimer is observed after the oxidative addition.
The monomeric σ-complexes generated by the oxidative addition of electrophilic arenes,
alkenes and alkanes to Pd(0) are electrophilic at the metal-substituted center, and can
therefore react with nucleophiles like alkenes.
6 | Chapter 1
1.2.1.2. Carbopalladation
The reaction of alkenes with σ-complexes generated by oxidative addition depends on the
ease of formation of the Pd(II)-alkene π-complex and/or the migration ability of the R (aryl,
alkyl, alkenyl…) group on the metal to the double bond of the olefin. Two distinctive
pathways (Scheme 1.3), which determine the regioselectivity and the stereoselectivity
outcome of the Heck reaction, have been proposed for the carbopalladation step in Heck-type
reactions.20 For the one being cationic, the olefin displaces the anionic species X–, or occupies the opened coordination site on the cationic metal center, while for the one being neutral, a two-electron-donating ligand is displaced by the olefin via an associative or a dissociative mechanism. A strongly coordinating counteranion X– will favor this last pathway, whereas
+ the cationic pathway would be favored when X = OTf or N2 .
Scheme 1.3. Cationic and neutral carbopalladation pathways.
In the cationic pathway, the π-complexation is favored with electron-rich olefins whose
insertion into the Pd-R bond is mainly electronically controlled leading to the formation of
branched products. For the neutral proposed pathway, the formation of the π-complex is
favored with electron-deficient olefins whose insertion into the Pd-R bond is mainly controlled
by steric factors leading to the formation of linear products. Thus, with polar alkenes such as Introduction | 7
acrylates, vinyl acetates, and acrylonitriles, the migration of the hydrocarbyl moiety onto the
terminal C(sp2) of the olefin is favored, whereas a 1,2-migratory insertion mode is preferred with vinyl ethers (Scheme 1.4). In any case, the migratory insertion of the olefin into the Pd–
R bond is considered to be a concerted process taking place via a planar four-centered transition state.
The carbopalladation reactions generate another σ-complex that can undergo a syn-β-hydride elimination, if a sp3-bonded hydrogen atom is present at the β position of the alkyl chain
attached to the palladium center.
Scheme 1.4. Dewar-Chatt-Duncanson orbitals interactions and regioselectivity in the carbopalladation in the carbopalladation of alkenes.21
1.2.1.3. β-Hydride elimination
The β-hydride elimination is the microscopic reverse of the migratory insertion of a hydride into a coordinated double bond and therefore requires a coordination vacancy on the palladium center and an access of the metal to the β-hydrogen of the alkyl chain. This may 8 | Chapter 1
require an internal Cα–Cβ bond rotation in the Pd(II)-alkyl bond. A relatively stable Cβ–Hβ agostic Pd complex thus formed. It is noteworthy that some palladium β-agostic alkyl complexes have been identified as resting state in some Pd-catalyzed polymerization of olefins, in equilibrium with the corresponding olefin complex.22 A planar four-centered transition state
would then be expected for the β-hydride elimination step. The more electrophilic the metal
center is, the more prone the Pd(II)-alkyl is to undergo reversible β-hydride elimination,
making this process the major limitation encountered in the Heck-type reactions when
aliphatic chains are attached to the metal. The obtained Pd(II)-hydride constitutes the last
Pd(II) species in the Heck cycle.
1.2.1.4. Base-assisted regeneration of the zero-valent palladium catalyst
The base-assisted Pd(0) regeneration occurs at the end of the catalytic cycle of a Heck reaction. The release of the alkenyl product is accompanied by the elimination of H–X from the Pd(II). The presence of a super-stoichiometric amount of base shifts the otherwise slow
process towards the formation of the catalytically active Pd(0).23 Moreover, the deprotonation
– formally a reduction of Pd(II) to Pd(0) – is made easier by the acidic nature of the hydridopalladium(II) intermediates. Relatively strong and weak bases (organic and inorganic)
have been utilized in Heck reactions to achieve this step. The zero-valent palladium metal tends to aggregate in the absence of stabilizing ancillary ligands.
1.2.1.5. Phosphine ligands in Heck-type Reactions
The stabilization of the Pd(0) species and thus the avoidance of the aggregation of metallic palladium constitute one of the primary functions of any stabilizing component in a Pd- catalyzed reaction. However, such a stabilization should not lead to a complete inactivation of the formed complex. Owing to their soft nature and tunable electronic and steric properties, phosphines have emerged as the supporting ligands of choice in combination with the soft low-valent Pd(0) for the development of a high activity Pd-catalyzed Heck-type reactions.24
Introduction | 9
Figure 1.2. Steric and electronics of the phosphine-palladium interactions.
The dative phosphine-palladium bond (Figure 1.2) consists of a σ-electron-donation from the phosphine to the empty d-orbital of Pd and a π-back-electron-donation from the filled d- orbital of the metal to the σ*-orbitals of the phosphine. The more electron-rich the substituents on the phosphine are, the more σ-donation to the metal and the less π-back- electron-donation it receives from the metal. The reverse is true for the electron-poor substituents on the phosphine ligand. The steric and additional electronic properties of the phosphine ligand are controlled by the so-called “cone angle”25 for the monophosphine and
the “bite angle”26 for the bidentate phosphine (Figure 1.2). These properties have impacted the understanding of the different steps of the Pd-catalyzed Heck reaction and other Pd- catalyzed cross-coupling reactions. Electron-donating and bulky phosphines have been found to accelerate the oxidative addition by favoring the formation of the catalytically active 12- electron-LPd(0) and increase the nucleophilicity of the metal center. Bidentate and bulky phosphine ligands also participate in the prevention of the occurrence of the β-hydride elimination when alkyl electrophiles are used, and in the acceleration of the reductive elimination in other cross-coupling reactions. However, the olefin coordination to the metal center can be retarded by the sterics and the electron-donating nature of the phosphine ligand, making it difficult to predict how the overall rate of Pd-catalyzed reaction is affected.
Although the original phosphine ligands used by Richard Heck were PPh3 and (o-tol)3P
(1.1a) for the coupling reaction, numerous phosphine ligands have been synthesized since and
showed outstanding catalytic performance in the reaction. Among these Pd-based phosphine
catalysts the Herrmann-Beller (HB) palladacycle 1.227 depicted in Figure 1.3, which was the 10 | Chapter 1
first palladacycle used in the Heck reaction, catalyzed the coupling of aryl bromides with
olefins in high TONs (∼200 000 in DMA27 and 1 000 000 in ionic liquids28). The excellent
activity of the catalyst has been largely attributed to its stability, under the often high
temperatures required for the Heck reaction, which prevents the facile aggregation of the Pd
metal into inactive Pd clusters.
Figure 1.3. Herrmann-Beller palladacycle.
1.2.1.6. Clusters of Palladium: Unexpected catalysts in the Heck reaction
The agglomeration of unstable poorly-stabilized Pd(0) leads to a gradual loss of the catalytic
activity over time of the homogeneous catalyst employed in the reaction. The palladium
nanoparticles (PdNPs) resulting from the agglomeration of Pd(0) can be reintroduced in the
catalytic cycle, or in a different and more favorable pathway, generate decomposed palladium
species. As such, colloidal or nanoparticles of palladium may be seen as a reservoir of soluble
ill-defined catalytically active Pd(0) species and the last form of the catalyst before it
completely deactivates.29 In their original 1971 article, Mizoroki and co-workers obtained good
catalytic activity in the Heck reaction using PdCl2 in the presence of some weakly stabilizing
anionic species. They reported the fast reduction of their Pd(II) to metallic Pd(0) in the course of the reaction and a high catalytic activity for the same coupling reaction when only metallic palladium was used as catalyst. Since then, numerous examples have shown that
PdNPs can also act as a relatively good catalyst in the Heck-type reactions. In some cases, the activity of the PdNPs in the coupling reactions was similar to the activity of some well- defined Pd catalysts. Introduction | 11
1.2.2. Carbopalladation reactions for the (co)polymerization of alkenes
The presence of late transition metals like palladium in polymer science originates from their
good tolerance towards functionalized olefins – a greater tolerance than that of early transition
metals – often used in combination with simple olefins in order to produce novel polyolefin
materials.30,11 The key requirements for an efficient metal catalyst are the presence of an
accessible coordination site for the incoming olefins and a higher rate of the coordination-
insertion of the olefins compared to the rate of the β-hydride elimination. For decades, the
activity of the late transition metals in the polymerization of olefins had been limited to the
formation of dimers or oligomers due to the relentless occurrence of the β-hydride elimination followed by the chain transfer process.31 Examples of Ni-based catalysts used to produce
short-length polymers are depicted in Figure 1.4.
Figure 1.4. Ni-based SHOP (Shell Higher Olefin Process) catalysts for the oligomerization of olefins.
In the 1990s Brookhart and co-workers discovered a Pd-based diimine system 1.3 (Scheme
1.5) able to produce long chains of highly branched (co)polymers of ethylene and a polar
alkene (MA) with 12% incorporation of the functionalized olefins.32
iPr iPr OMe N O Pd N CO 2Me iPr iPr
CO 2Me 1.3 x z + CH Cl , 35 °C, 18.5 h y 2 2 n MA incorporation 12% Scheme 1.5. Copolymerization of MA with ethylene with the Brookhart’s Pd-based system. 12 | Chapter 1
The use of a bulky diimine ligand and the electrophilic nature of the cationic metal center
are among the key features favoring the formation of long chain (co)polymers.30 For this, the
bulkiness of the ligand should be designed in such a way that the axial faces of the square
planar complex are blocked, retarding the associative chain transfer that favor shorter
polymeric chains. However, successive β-hydride elimination, rotation of the resulting olefin
around the Pd–H bond, and hydride-reinsertion, even at low temperatures, lead to chain-
walking and do not allow the exclusive formation of linear polymers (Scheme 1.6).
Scheme 1.6. Proposed mechanism for the Pd-diimine catalyzed polymerization of olefins.
Owing to the early investigations on their initial SHOP systems able to produce linear
oligomers, the beginning of the 21th century is marked by the discovery of the anionic
phosphine sulfonate (P∼O) ligands by Shell chemists.33 Combined with palladium, phosphine- sulfonate ligands exhibit a high potential for the incorporation of polar olefins. Typical
(co)polymerization conditions are depicted in Scheme 1.7; they require higher temperatures
compared to the Brookhart’s systems. The final olefins formed are linear, with a higher degree
of incorporation of polar olefins. Mechanistic investigations on the migratory insertion
polymerization suggest the occurrence of cis/trans isomerizations to give the intermediate 1.6
in Figure 1.5.34,11 The weak σ-donor and to some extent the weak π-acceptor nature of the Introduction | 13
sulfonate group result in a favourable binding of olefins trans to it. The phosphine moiety is a strong σ-donor and therefore enhances the migration ability of the substituent at its trans
position. The destabilization of an alkyl group at that position leads to a relatively fast
insertion to the coordinated olefin. End-group analysis of the outcome of the
(co)polymerization using phosphine sulfonate ligand-Pd system shows that chain growth
process competes with β-hydride elimination and chain transfer. The loss of catalytic activity
by the formation of metallic deposit of palladium is another major drawback in this catalysis.
Scheme 1.7. Copolymerization of MA with ethylene using the in situ made phosphine sulfonate (P∼O)Pd catalyst in A) and the well-defined (P∼O)Pd catalyst in B).
Figure 1.5. Proposed reactive intermediate before the migratory-insertion. 14 | Chapter 1
1.2.3. Carbopalladation reactions for the cyclopropanation of alkenes
The most common and first catalytic intermolecular cyclopropanation of alkenes using
palladium is by the decomposition of diazocompounds. The cyclopropanation of alkenes by
decomposition of ethyl diazoacetate, the first diazocompound investigated for this
transformation with palladium was reported by Armstrong et al. in 1966.35 Before this
discovery, the only transition metals able to efficiently catalyze this transformation were
copper salts.36 Rhodium was also shown to form cyclopropane quantitatively from alkenes via
37 decomposition of diazocompounds. Several classical palladium sources such as PdCl2,
(PPh3)4Pd and Pd(OAc)2 have been successfully applied as catalysts in this reaction with
various olefins and diazocompounds.38 The formation of the metal carbene is an important
feature of the mechanism of the reaction, regardless of the transition metal used. In the
presence of alkenes, investigations clearly point to a carbometalation pathway, when the metal used is palladium, with the formation of the palladacyclobutane intermediate 1.8 in
Scheme 1.8, whereas a carbenoid-type mechanism is proposed for rhodium and copper, except
when associated to weak ligands such as triflates or tetrafluoroborates like in Cu(OTf) or
38a Cu(BF4)2, respectively, in which case a carbometalation pathway is favored.
Scheme 1.8. Representative catalytic cycle for the metal catalyzed cyclopropanation of olefins by decomposition of diazomethane. Introduction | 15
Other cyclopropane formations by palladium catalysis in the absence of diazocompounds proceeding via carbometalation have also been reported. Different reagents have been used to cyclopropanate norbornene (NBE) and derivatives in fair to excellent yield, usually in the presence of an excess of olefins (Scheme 1.9).39 Among the reagents employed and shown in
Scheme 9, the iodomethylstannate reagent 1.11,39c which is based on the toxic tin metal is the only methylene “CH2” donor and therefore the only potential candidate for the replacement of diazomethane.
Scheme 1.9. Reagents reported in the literature for the Pd-catalyzed cyclopropanation of norbornene. 16 | Chapter 1
1.3. Aims of the thesis
The ultimate aim of this thesis is to contribute to the development and to gain an improved
understanding of the catalytic intermolecular carbopalladation reactions directed towards the preparation of (co)polymers of polar monomers and of cyclopropanes from electron-rich alkenes.
The investigation of the processes that are crucial for a better understanding of the limited activity observed in some palladium-catalyzed methods used for the synthesis of functionalized organic compounds and polymers can further contribute to the development of more robust catalytic systems. In this regard, the primary objective of this thesis is dedicated to the investigation of a potential pathway likely to be the major palladium catalyst deactivation pathway in the (co)polymerization of polar olefins when phosphine sulfonates are used as ligands. Gaining insight into the in situ generation of the Pd(0) species, which are believed to be involved in the main deactivation pathway, as well as the study of their reactivity toward electrophilic reagents will be important starting points in the design of a
Pd-catalyzed living (co)polymerization of polar alkenes with desired end-groups.
The second goal of this thesis is directed towards the study of a new palladium-catalyzed methodology for the electrophilic cyclopropanation of alkenes developed in our laboratories.
The development of this reaction was based on a designed mechanistic model. Preliminary studies on this new reactivity of the palladium catalysts led to the development of a procedure giving excellent results in the cyclopropanation of norbornene. Firstly, the observation and identification of relevant reaction intermediates will enable the validation of the mechanistic model from which the catalytic reaction was developed. Secondly, a strategy intended to overcome the limitations encountered with the new methodology will be developed and will allow improvement of the reactivity of less reactive electron-rich alkenes.
Introduction | 17
1.4. Outline of the thesis
The results of the studies presented in this thesis are divided into three chapters (Chapter
2-4). The final chapter (Chapter 5) will conclude the thesis and provide some final thoughts
both on what has been done and how the research presented herein could be taken forward.
The research embodied in this thesis has been undertaken in the frame of a Swiss National
Science Foundation grant titled "Spectroscopy and Design of Organometallic Catalysts"
(project no. 137505).
The deactivation pathways for systems in which a loss of the catalytic activity over time is apparent are often either not studied or not well understood. Chapter 2 of this thesis details
our attempt to identify, generate, and study the intermediates that are relevant for the
understanding of the deactivation process of the metal catalyst taking place during phosphine
sulfonate-based carbopalladation of polar olefins to (co)polymers, with a strategy proposed for the regeneration of the palladium catalyst before it deactivates irreversibly.
Chapter 3 introduces the newly developed palladium-catalyzed cyclopropanation of electron-
rich alkenes, here norbornene, with the aim to investigate, by means of spectroscopic
techniques, the mechanism by which the catalysis takes place. Density Functional Theory
(DFT) results serve as a support to the proposed mechanistic model.
In Chapter 4, we report our investigations on the different reactive components of the
cyclopropanation reaction and show how the findings impact the strategy adopted to expand
the scope of the reaction.
The last chapter (Chapter 5) summarizes the studies presented in the thesis, discusses the
approaches, results, and limitations of these studies and proposes some future directions this
work may take.
18 | Chapter 1
1.5. References
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3 Negishi, E., Handbook of Organopalladium Chemistry for Organic Synthesis; John Wiley &
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9 Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467–4470.
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; Angew. Chem. Int. Ed. Engl. 1995, 34, 1348–1350 ; (b) Louie, J.; Hartwig, J. F. Tetrahedron
Lett. 1995, 36, 3609–3612.
11 Nakamura, A.; Ito, S.; Nozaki, K. Chem. Rev. 2009, 109, 5215–5244.
12 Zhang, Y.; Wang, J. E. Eur. J. Org. Chem. 2011, 1015–1026.
13 Kikukawa, K.; Matsuda, T. Chem. Lett. 1977, 159–162.
14 (a) Fleckenstein, C. A. ; Plenio, H. Chem. Soc. Rev. 2010, 39, 694–711; (b) McMullin, C.
L.; Jover, J.; Harvey, J. N.; Fey, N. Dalton Trans. 2010, 39, 10833–10836; (c) Ahlquist, M.;
Fristrup, P.; Tanner, D.; Norrby, P.-O. Organometallics 2006, 25, 2066–2073; (d) Senn, H.
M.; Ziegler, T. Organometallics 2004, 23, 2980–2988; (e) Goossen, L. J.; Koley, D.; Hermann,
H.; Thiel, W. Chem. Commun. 2004, 2141–2143; (f) Espinet, P.; Echavarren, A. M. Angew.
Introduction | 19
Chem. Int. Ed. 2004, 43, 4704–4734; (g) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000,
33, 314–321; (h) Amatore, C.; Pfluger, F. Organometallics 1990, 9, 2276–2282; (i) Kochi, J.
K., Organometallic Mechanisms and Catalysis: The Role of Reactive Intermediates in Organic
Processes; Academic Press, New York, 1978, pp 138–183.
15 Rudolph, A.; Lautens, M. Angew. Chem. Int. Ed. 2009, 48, 2656–2670.
16 Ariafard, A.; Lin, Z. Organometallics 2006, 25, 4030–4033.
17 DeTar, D. F.; McMullen, D. F.; Luthra, N. P. J. Am. Chem. Soc. 1978, 100, 2484–2493.
18 (a) Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131,
8141–8154; (b) van Strijdonck, G. P. F.; Boele, M. D. K.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M. Eur. J. Inorg. Chem. 1999, 1073–1076.
19 Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996, 15, 2755–2763.
20 (a) Bäcktorp, C.; Norrby, P.-O. Dalton Trans. 2011, 40, 11308–11314; (b) Andappan, M.
M. S.; Nilsson, P.; von Schenck, H.; Larhed, M. J. Org. Chem. 2004, 69, 5212–5218; (c)
Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2–7; (d) Cabri, W.; Candiani, I.; Bedeschi,
A. J. Org. Chem. 1993, 58, 7421–7426.
21 Espinet, P.; Albéniz, A. C., Fundamentals of Molecular Catalysis. Current Methods in
Inorganic Chemistry, vol. 3; ed. Yamamoto A. and Kurosawa H., Elsevier, Lausanne, 2003, ch. 6, pp. 293–371.
22 Kogut, E.; Zeller, A.; Warren, T. H.; Strassner, T. J. Am. Chem. Soc. 2004, 126, 11984–
11994 and the references therein.
23 Jutand, A., The Mizoroki-Heck Reaction; Oestreich, M., Ed.; Wiley: Chichester, 2009, pp
1–50.
24 Colacot, T. J., New Trends in Cross-Coupling: Theory and Applications; Ed.; RSC:
Cambridge, U.K., 2015.
25 Tolman, C. A. Chem. Rev. 1977, 77, 313–348.
26 Casey, C. P.; Whiteker, G. T. Isr. J. Chem. 1990, 30, 299–304.
27 Herrmann, W. A.; Brossmer, C.; Öfele, K.; Reisinger, C.-P.; Priermeier, T.; Beller, M.;
20 | Chapter 1
Fischer, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 1844–1848.
28 Herrmann, W. A.; Böhm, V. P. W. J. Organomet. Chem. 1999, 572, 141–145.
29 Consorti, C. S.; Flores, F. R.; Dupont, J. J. Am. Chem. Soc. 2005, 127, 12054–12065.
30 Camacho, D. H.; Guan, Z. Chem. Commun. 2010, 46, 7879–7893.
31 Ittel, S. D.; Johnson, L. K.; Brookhart, M. Chem. Rev. 2000, 100, 1169–1203.
32 (a) Johnson, L. K.; Mecking, S.; Brookhart, M. J. Am. Chem. Soc. 1996, 118, 267–268;
(b) Mecking, S.; Johnson, L. K.; Wang, L.; Brookhart, M. J. Am. Chem. Soc. 1998, 120,
888–899; (c) Ittel, S. D.; Johnson, L. K.; Brookhart, M. Chem. Rev. 2000, 100, 1169–1204.
33 Drent, E.; van Dijk, R.; van Ginkel, R.; van Oort, B.; Pugh, R. I. Chem. Commun. 2002,
744–745.
34 Nakamura, A.; Anselment, T. M. J.; Claverie, J.; Goodall, B.; Jordan, R. F.; Mecking, S.;
Rieger, B.; Sen, A.; van Leeuwen, P. W. N. M.; Nozaki, K. Acc. Chem. Res. 2013, 46, 1438–
1439.
35 Armstrong, R. K. J. Org. Chem. 1966, 31, 618–920.
36 (a) J. Hine, "Divalent Carbon", The Ronald Press Co., New York, N.Y., 1964, pp 108–156;
(b) Kirmse, W., Carbene Chemistry; Academic Press, New York, N.Y., 1964; (c) Kirmse, W.,
Carbene Chemistry, 2nd ed; Academic Press, New York, N.Y. 1971.
37 Paulissen, R.; Reimlinger, H.; Hayez, E.; Hubert, A. J.; Teyssie, P. Tetrahedron
Lett. 1973, 2233–2236.
38 (a) Doyle, M. P. Chem. Rev. 1986, 86, 919-939; (b) Lautens, M.; Klute, W.; Tam, W.
Chem. Rev. 1996, 96, 49–92.
39 (a) Trost, B. M.; Schneider, S. J. Am. Chem. Soc. 1989, 111, 4430–4433; (b) Ogoshi, S.;
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Kobayashi, R.; Abe, H. Eur. J. Org. Chem. 2014, 7818–7822.
Chapter 2
Phosphine Sulfonate Pd–Based Catalysts: From the
Deactivation to the Regeneration in Situ
2.1. Introduction
2.1.1. Motivations
The highly electrophilic homogeneous Ziegler-Natta and other early transition metal-based
catalysts used in industry for the polymerization of non-polar monomers are rapidly poisoned
by the functional group of polar olefins.1 Functionalized polyolefins are known to provide
good adhesion, wettability, printability, dyeability and excellent gas barrier properties, among
others. Presently, commercial processes for the (co)polymerization of polar olefins with
ethylene mainly require high pressure radical processes which lead to a poor control of the
polymer length and architecture.2 The discovery that the combination of the palladium
catalyst 1.5a, based on the phosphine sulfonate ligand, affords a catalytic system able to
incorporate ca. 52% of methyl acrylate into a linear polyethylene polymeric chain (Scheme
1.7) marked a major step towards an industrial application for the carbopalladation reaction of useful polar monomers in polymer science. Furthermore, homopolymerization of MA using the same catalyst 1.5a has been shown to give a significant amount of short-length Me- end and H-end polymeric material, with linear pentamers of MA as major oligomers 22 | Chapter 2
(Scheme 2.1).3
Scheme 2.1. Homooligomerization of MA using the DMSO-bound (P∼O)Pd catalyst.
The maximum turnover number (TON) for the copolymerization of ethylene and MA was
reported to be close to 4000, decreasing with the increased amount of MA. For the MA-
oligomerization a maximum TON of 100 can be reached. The low TONs obtained in these
(co)polymerizations represent the major limitation of this catalytic system. The
(co)polymerization reactions of MA using (P∼O)Pd-based catalysts are always characterized
by the deactivation of the metal catalyst by degradation. It represents the main deactivation
process and is observed to be irreversible.4 Catalyst deactivation is a problem of great and continuing concern in industry, as most of the promising catalytic reactions fail to make the
transfer between their discovery or development in academia to the chemical industry due to
the poor TONs, where stability of the catalysts is one of the major reasons but not the only
one. 5 The physical sign of the deactivation of the Pd-based catalysts used in the
(co)polymerization of olefins is the formation of metallic black palladium, common to many
Pd-based reactions. However, information about the catalysts decomposition pathways is
scarce.6 The irreversible deactivation leading to the formation of black palladium had never
been investigated at the time of our investigations.7
2.1.2. Hypothesis
Our study of the deactivation pathway was based on the hypothesis that due to the significant amount of β-hydride elimination, the main species expected to be present in solution are the Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 23
Pd–hydride species 2.1. These hydrides are acidic8 and would therefore be in equilibrium
with the reactive anionic palladium intermediates 2.3 (the deprotonated form of the
intermediates 2.2) – formally an equilibrium between Pd(II) and Pd(0). Our goal was to
generate and study the reactivity of intermediates of type 2.2 or 2.3 with the ultimate aim to rescue the (co)polymerization catalyst in situ with suitable electrophiles before it enters
the deactivation pathways, thus significantly increasing the TON of these reactions.
Scheme 2.2. Postulated equilibrium between the (P∼O)Pd–hydride and its acidic forms.
2.2. Generation of complexes Pd(P∼O)(H)
Olefin (co)polymerization using either the in situ-prepared or the well-defined catalyst should
follow the same catalyst degradation mechanism as similar palladium species would be present
in their reaction mixture. However, studies on the catalyst lifetime by Jordan and co-workers
have shown that the initial conditions reported by Drent et al. exhibited a lower catalyst
lifetime than the conditions in which a discrete catalyst is employed.4
The mixture of the acidic (P∼O)H with Pd(dba)2 dissolved in dry DMF or DMA at ambient
31 temperature generated a single and sharp peak in the P NMR (DMF-d7) spectrum at
δ ∼12.3 ppm. No signal of the free phosphine (P∼O)H was observed. A signal corresponding
1 to the acidic proton was present in the H NMR (DMF-d7) spectra at δ ∼11.6 ppm (see Figure
2.3). It therefore appeared that the species formed in solution is 2.4 (Scheme 2.3). It is
noteworthy that the position of the proton in the (P∼O)H ligand had always been assumed
to be on the phosphorus rather than the oxygen based on the fact that a P–H coupling was
present in some of the ligands, but also on the assumption that the pKa of benzenesulfonic
acid is lower than that of the acidic triaryl/alkylphosphines, independently of the nature of the aryl/alkyl groups on the phosphines in question.9 However, on the one hand, the reported
10 experimental pKa of benzenesulfonic acid in water is 0.70 (theoretical pKa of 1.08) while 24 | Chapter 2
that of PPh3 was measured to be lower than 1.1 in MeCN/H2O (85:15, v/v) and suggested to be lower than 0.10 in water.11 On the other hand, no P–H coupling was observed in the
NMR of the ligand 1.4a used in our study. For the same reason, the neutral species had
already been suggested to be the actual form in solution.12 Therefore, we decided to draw the
(P∼O)H ligand 1.4a and the complex 2.4 in their neutral forms instead of their respective zwitterionic analogues.
Scheme 2.3. Generation of Pd(P∼O)H type species.
The electrospray ionization tandem mass spectrometry (ESI–MS) analysis of the reaction mixture diluted in DCM in the negative mode allowed the detection of the anionic species
2.5, m/z –741, corresponding to the basic form of 2.4 (Figure 2.1). The latter gave upon collision induced dissociation (CID, Figure 2.2) the reactive anionic fourteen-electron-
(P∼O)Pd intermediate 2.3, m/z –507, which can also be formed in the source CID. Similar spectroscopic observations (by NMR and ESI–MS) were made when a mixture of (P∼O)Na and Pd(dba)2 reacts with 1 equiv. of trifluoroacetic acid (TFA) at ambient temperature. Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 25
Figure 2.1. ESI mass spectrum of the mixture of (P∼O)H + Pd(dba)2.
Figure 2.2. CID spectrum on the ion (P∼O)Pd(dba)–, m/z –741. Collision gas pressure: 0.5 mTorr, Collision Energy: 25 V.
26 | Chapter 2
Further equimolar addition of PPh3 to an NMR tube containing 2.4 in DMF-d7 led to the
1 observation of a hydride containing species in H-NMR (DMF-d7) spectrum characterized by
2 a doublet at δ –17.1 ppm with a coupling constant of JHP = 14.5 Hz in the case of PPh3.
This should correspond to the coupling of the coordinated PPh3 cis to the hydride 2.6a. The absence of a cis coupling between the (P∼O) phosphine and the hydride was unexpected given that similar cis P–H coupling, although relatively small, had been observed from the (t-Bu)3P-
bound (P∼O)Pd–hydride.7
31 The P NMR (DMF-d7) of the solution showed the presence of two doublets arising from the
2 coupling of the two phosphines trans to each other (δ –8.1 ppm, JPP = 388.7 Hz and
2 δ 24.8 ppm, JPP = 388.7 Hz, Figure 2.4) as well as unidentified peaks. Similarly, doublets of
2 2 lower intensity at δ –19.1 ppm, JHP = 4.2 Hz in DMF-d7 and δ –19.2 ppm, JHP = 4.7 Hz in
CD2Cl2 (see Appendix A), which would correspond to the palladium hydride 2.6b (Scheme
2.4) were observed in the proton spectrum after addition of excess (≥ 20 equiv.) pyridine to a DMF-d7 and CD2Cl2 solution of (P∼O)H + Pd(dba)2, respectively. These results support
the hypothesis that an oxidative addition/reductive elimination equilibrium between the
palladium species 2.1 and 2.2 (or 2.3) exists.
Scheme 2.4. Generation of PdH(P∼O) type species. Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 27
MeO 2 H P II Pd S O PPh3 O O 2.6a
1 Figure 2.3. H NMR spectra of 2.4 and in situ-generated 2.6a in DMF-d7.
MeO 2 H P II Pd S O PPh3 O O 2.6a
31 Figure 2.4. P NMR spectrum of in situ-generated 2.6a in DMF-d7. 28 | Chapter 2
2.3. Reactivities of complexes Pd(P∼O)H
2.3.1. Thermolysis of a solution of complex 2.4
High temperatures lead to the deactivation of the Pd catalysts.5,13 Deposition of palladium black was observed upon thermolysis at 90 °C of a DMF-d7 solution of the complex 2.4. A
broad signal was observed at δ 23.6 ppm, corresponding to the stable and poorly soluble
(P∼O)Pd bis-chelate complex 2.7 (see Figure 2.5). The bis-chelate complex 2.7 was inactive
in the polymerization. Similar inactive bis-chelates were observed with other late transition
metal catalysts2 and already represented a challenge in the polymerization reaction. However,
no signal of the free (P∼O)H ligand was observed in the 31P NMR spectrum.
31 Figure 2.5. P NMR spectra of the thermolysis of 2.4 generated in situ in DMF-d7. Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 29
2.3.2. Reactivity of complex 2.4 towards MA
MA reacted spontaneously with the in situ-prepared 2.4 at ambient temperature in DMF-d7
leading to the migration of the hydride to the MA double bond in an expected 2,1-insertion
fashion to give the complex 2.8a in Scheme 2.4 (δ 25.0 ppm in the 31P NMR), presumably
via a first O–H oxidative addition. Complex 2.8b was formed by addition of pyridine to the
mixture. The proton NMR of the product showed the signal of the β-protons of inserted MA
3 at δ 0.33 ppm coupling with the α proton and the phosphorus of the ligand ( JHH = 7.0 Hz
3 3 3 and JHP = 4.6 Hz). A doublet of quartet ( JHH = 7.0 Hz and JHP = 10.4 Hz) was observed
at δ 2.16 ppm and corresponds to the proton at the α position. The complex 2.8b could be
isolated in 50% yield from a DMA mixture of 1 equiv. of 1.4a and 1.05 equiv. of Pd(dba)2 to which 3 equiv. of MA and 2 equiv. of pyridine were added. At the end of the work up procedure, a slow evaporation of the solvent (CH2Cl2/Et2O) on the rotary evaporator at a
temperature lower than 0 °C (absence of water bath at high vacuum) provided some yellow
crystals suitable for analysis by X-ray diffraction. The molecular structure of 2.8b is shown in Figure 2.6 and confirmed the structural assignment made from solution NMR spectroscopy.
No close interactions between the β–hydrogens and the metal center were observed in the solid-state structure of 2.8b. The Pd−H7b and Pd−H7c distances are approximately 2.969 and 3.063 Å, respectively, which are significantly greater than the sum of the Van der Waals
14 radii of Pd and H (rw(Pd) + rw(H) = 2.830 Å). The hydrogen atom H7a is positioned anti
with respect to the Pd center and is also not interacting with the metal center. The stability
of the complexes 2.8a and 2.8b may come from the favorable interaction between O2 and
H16, which are separated by a distance of 2.515 Å, being shorter than the Van der Waals
radii of O and H (rw(O) + rw(H) = 2.720 Å). Similar MA-mono-inserted (P∼O)Pd complexes
(1,2- or 2,1-MA-inserted products), either into a Pd–Me, Pd–Ph or Pd–H bonds have been made in situ after a β-hydride elimination step and characterized by NMR.3,12,15 The complex
2.8b is the first and only complex characterized by its X-ray structure for this family of MA-
mono-inserted (P∼O)Pd complexes. 30 | Chapter 2
MeO 2 P 0 Pd(dba) S O O O O O O H MeO O 2 MeO P 2 CO2Me 2.3 (1 equiv.) II 2 equiv. pyridine P II Pd Pd DMF-d , RT, 10 min 50% 3 equiv. 7 S O Solv S O Pyr O O O O 2.8a 2.8b Scheme 2.5. Migratory insertion reaction of MA and synthesis of complexes 2.8a and 2.8b.
Figure 2.6. Crystal structure of complex 2.8b at 30% thermal ellipsoids. Solvents are omitted for clarity. Selected bond lengths (Å) and angle (deg) of 2.8b: Pd1−P1 = 2.2574(8); Pd1−C8 = 2.068(3); Pd1−O7 = 2.1246(19); Pd1−N1 = 2.105(2); Pd1−C8−C7 = 108.5(2).
2.3.3. Reactivity of complex 2.4 towards electrophiles of type R-X
In situ-generated species 2.4 were found less reactive than their anionic conjugate base. While
the oxidative addition of 1.1 equiv. of phenyl iodide to 2.4Na proceeds readily at room
temperature, the addition of up to 100 equiv. of PhI appeared to be extremely slow with 2.4:
no product of the oxidative addition was observed after prolonged time (∼3 h) at ambient
temperature (Scheme 2.6). However, addition of 2 equiv. of 4-(diazonium)benzenesulfonate to a DMA solution of 2.4 gave the product of the oxidative addition in the Matsuda-Heck Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 31
cross-coupling as the only product observed in the 31P NMR spectrum. The oxidative addition
should be preceded by the deprotonation of the complex 2.4 to form a more reactive anionic intermediate. The polymerization catalysts can be regenerated using the same principle. An
X-ray diffraction of a single crystal of the product (2.9) of the fast oxidative addition of benzyl bromide with 2.4Na at ambient temperature is presented in Figure 2.7. The sodium cation is stabilized by three tetrahydrofuran molecules while interacting with the bromide and one of the oxygen of the sulfonate group. The bromide atom is located trans to the phosphorus moiety whereas the benzyl group is trans to the sulfonate group. The location of the bromide trans to the phosphorus is expected to favour the release of NaBr in the presence of strongly coordinating solvents like acetonitrile or pyridine, or an alkene. The coordination of the sulfonate group to Pd is weaker than in complex 2.8b, as confirmed by the long distance between Pd1 and O5 (2.192(3) Å against 2.1246(19) Å for the complex 2.8b). The product 2.9 represented the major phosphorus-containing species in solution (δ 17.98 ppm in
THF-d8) alongside a signal at δ 32.71 ppm (10:1 ratio) which could be assigned as the benzyl
13,16 phosphonium salt consecutive to a P–Cbenzyl reductive elimination from the metal Pd. A similar phosphonium salt was also observed when MeI was used as electrophile and may represent a limitation of the regeneration when alkyl halides are used.
Scheme 2.6. Reactivity of complexes 2.4 and 2.4Na towards electrophiles of type R–X. 32 | Chapter 2
Figure 2.7. Crystal structure of complex 2.9 at 30% thermal ellipsoids. Hydrogen atoms and some residual solvents are omitted for clarity. Selected bond lengths (Å) and angle (deg) of 2.9: Pd1−P1 = 2.2454(10); Pd1−C31 = 2.111(4); Pd1−O5 = 2.192(3); Pd1−Br2 = 2.5123(5); O5−Na3 = 2.381(3); Br2−Na3 = 3.0696(17); Pd1−C31−C32 = 109.7(3).
The strategy consisting on a deprotonation of the intermediates of type 2.3 followed by an oxidative addition could be used to extend the catalyst lifetime and potentially to produce a large variety of polymers with different end-groups. An attempt to regenerate the catalyst in situ in the presence of benzenediazonium tosylate (22.5 µmol) and an internal standard
(dodecane, 9 µmol) in a typical MA-homopolymerization condition (4.5 µmol of catalyst, 4 mol L–1 of MA in toluene, 95 °C, 1 h) using the catalyst 1.5b (Scheme 2.7), which was
prepared from the oxidative addition of MeI on 2.4Na, led to the observation of methyl
cinnamate, the Matsuda-Heck product of the reaction between the diazonium salt and MA,
as the only species in GC–MS (∼80% GC yield relative to the diazonium salt). Traces of
oligomers (6 maximum consecutive MA inserted) were observed on the ESI–MS. Hence, an
important condition to make the catalyst regeneration relevant with these systems was to
reduce the occurrence of the β-hydride elimination. Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 33
Scheme 2.7. Homooligomerization of MA in the presence of a diazonium salt.
2.4. Studies on the β-hydride elimination of complex 2.8
2.4.1. Qualitative ESI–MS study
Analogously to the ligand substitution or the chain transfer processes,17 two limiting and
distinguishable mechanisms for the β-hydride elimination (the microscopic reverse of the
hydride migration step) of 2.8 were conceivable.18 The first proposed mechanism (Scheme
2.8A) does not involve a ligand dissociation, i.e. through a five-coordinate intermediate,
known to be disfavored in most palladium systems, whereas in the second mechanism (Scheme
2.8B), the ligand dissociation occurs leaving a vacant coordination site on the transition metal
catalyst prior to the β–hydride elimination.
Scheme 2.8. Possible pathways for the β-hydride elimination of complex 2.8. 34 | Chapter 2
Qualitative ESI–MS/MS studies using an inert gas can offer insight into the structural
properties and the chemical processes, such as bond dissociations and/or internal
rearrangement prior to dissociation of different species subjected to collisional activation in
the absence of solvent effects.19 For these studies, the presence of a charge tag is required.
Therefore, we decided to carry out a qualitative β-hydride elimination study from the
prepared mono-inserted MA-Pd complex 2.8b using ESI–MS in the negative mode after
substitution of pyridine with the meta-sulfonatophenyl diphenylphosphine sodium salt
2.10Na. Anionic species 2.8c, m/z –935, were generated predominantly, mass-selected and
subjected to CID with a low pressure of argon gas in the collision cell (Figure 2.8). At mild
collision offset of –15.0 V (center-of-mass frame), two signals at m/z –849 (Figure 2.8A) and
m/z –341 (Figure 2.8B) appeared, which we ascribed to the palladium hydride ion 2.6c and
the negatively charged ligand 2.10, respectively. It should be noted that 2.6c could be in
equilibrium with the OH reductive elimination product. A release of the anions 2.10 from
2.6c is not excluded. The β-hydride elimination (channel A) takes place through a tight
transition state whereas the dissociation of the ligand (channel B) is governed by a loose
transition state, in agreement with the Rice-Ramsperger-Kassel-Marcus theory (RRKM)
theory.20
Similarly, in the positive mode, the substitution of pyridine was done with the (benzo-15-
crown-5)diphenylphosphine ligand. In the presence of NaBArF24, the resulting solution was
diluted in methanol and electrosprayed to produce the ions 2.8d, m/z 1069, which appeared as the major ions in the mass spectrum (Figure 2.9). The cation was mass-selected and CID
performed at a pressure of 0.5 mTorr of argon gas. At a collision offset of 30 V (center-of-
mass frame), two product signals appeared with m/z 983 (Figure 2.9A) and m/z 476 (Figure
2.8B), respectively assigned as the palladium hydride 2.6d and the free cationic sodiated ligand 2.11.
Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 35
Figure 2.8. CID experiments of complex 2.8c.
36 | Chapter 2
Figure 2.9. CID experiments of complex 2.8d.
Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 37
To conclude the study, we can say that in both cases, the gas phase investigations showed a
competition between the ligand dissociation (and possible subsequent β-hydride elimination
via pathway B in Scheme 2.8) and the β-hydride elimination via pathway A (Scheme 2.8).
Because the rate of a tight process, here the β-hydride elimination, was less accelerated by
the increase in the internal energy in comparison with a loose process, such as ligand
dissociation,21 these qualitative ESI-MS/MS studies suggested that the associative β-hydride
elimination mechanism (pathway A) should have a lower TSbarrier than the ligand dissociation
for the coordinating ligand used in our studies. The release of the anionic (P∼O) ligand was
not observed under the CID conditions making the complete opening of the chelate less likely.
Moreover, the syn-coplanarity between the Pd–Cα and Cβ–Hβ bonds required for the β-hydride
elimination to take place22 suggested a partial or full displacement of either the ligand L
(phosphines 2.10 and 2.11 and to some extent pyridine, or an olefin in solution) or the polar alkyl group into the apical position of the palladium center.
2.4.2. NMR Reaction Monitoring of the thermolysis of complex 2.8
Thermolysis of similar catalysts possessing a β-hydrogen was reported to form the alkene and palladium black. The decomposition of 2.8b could monitored by 1H NMR spectroscopy as a
function of time and temperature in a TCE-d2 solution, following the disappearance of the
Me signals (δ 0.33 ppm) of 2.8b. At temperatures varying from 85 °C to 95 °C in less than
2 h, the thermolysis resulted in similar observations: a second order kinetic profile with
respect to the palladium complex 2.8b, with deposition of palladium black in the NMR tube.
However, no black deposit was observed at 105 °C. Deposit of yellow small crystalline solid
corresponding to the complex 2.13 (δ 5.5 ppm in the 31P NMR. X–ray crystal structure
represented in Figure 2.10) resulted from the thermolysis. An over-all first order kinetic profile
–4 – 1 with respect to the palladium complex 2.8b was obtained with a kobs = (5.33 ± 0.12)·10 s
(Figure 2.11). 38 | Chapter 2
Figure 2.10. Crystal structure of complex 2.13 at 30% thermal ellipsoids. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) of 2.13: Pd1−P4 = 2.2478(5); Pd1−Cl2 = 2.2733(5); Pd1−O1 = 2.0419(12); Pd1−N10 = 2.1106(14).
Figure 2.11. Reaction rate for the degradation of the catalyst 2.8b at 105 °C in TCE-d2.
The formation of the thermally robust complex 2.13 could come from the deuterated solvent,
TCE being the probable source of chlorine atoms.23 Noda et al.24 observed the formation of a similar palladium chloride in chlorinated solvents from the corresponding Pd–alkyl and suggested its formation to be consecutive to a homolytic cleavage of the Pd–alkyl bond and Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 39
abstraction of chlorine atom from the solvent. Signals corresponding to methyl acrylate and
methyl propionate were present in the proton NMR at the end of the experiment (Figure
2.12). A homolytic cleavage would also lead to the formation of methyl 2-chloropropanoate, whose signals were not present in the 1H NMR. We proposed therefore that methyl propionate
is formed by protonolysis of 2.8b with HCl generated after the oxidative addition of TCE on
2.3b and subsequent β-chloride elimination from 2.12 (Scheme 2.9). The oxidative addition
of TCE followed by β-chloride elimination will also form the stable complex 2.13.25 At 105 °C, these processes may outrun the reverse hydride insertion reaction and irreversible deactivation pathways. Under these conditions, kobs would therefore corresponds to the rate of the β‑hydride elimination kβH. Traces of methyl propionate were also observed at lower tem- peratures (85 – 95 °C). These results confirmed our hypothesis that the in situ catalyst regeneration would be feasible with good electrophiles able to add oxidatively to Pd(0) generated during the polymerization process and made synthetically useful for any (P∼O)Pd- based (co)polymerization of olefins.
Figure 2.12. 1H NMR spectrum taken at the end of the reaction monitoring. 40 | Chapter 2
Scheme 2.9. Plausible mechanism for the formation of complex 2.13 and methyl propionate at 105 °C.
In conclusion, the β-hydride elimination process was enhanced by the high temperature and/or the presence of a vacant or coordination site in the axial position of the Pd metal center. The resulting Pd(II) hydride was in equilibrium with its acidic form. For any improvement of the (co)polymerizations catalyzed by the (P∼O)Pd system, priority should
be put on strategies allowing to reduce the frequency of occurrence of the β-hydride
elimination. One of these potential strategies has already been used in the Brookhart diimine
system and consists of blocking the axial face(s) of the metal center with bulky substituents
to limit the occurrence of the β-hydride elimination and the chain transfer process.26
2.5. Ligand design for the reduction of β-hydride elimination
2.5.1. Hypothesis
The 3D view of a typical (P∼O)Pd-based catalyst is presented with the molecular structure of MeCN-bound (P∼O)PdPh complex 2.14 in Figure 2.9. 2.14 was prepared in 90% by the treatment of a mixture of Pd(dba)2 and the sodium salt of the (P∼O)H ligand with an excess of phenyl iodide (3 equiv.) at ambient temperature in THF followed by halide abstraction in Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 41
the presence of MeCN. The solid-state structure of 2.14 in Figure 2.13 highlighted the absence
of steric hindrance in one of the axial coordination site of the palladium center. The distance
between Pd1 and H25 was measured to be 2.881 Å, longer than the sum of the Van der Waals
radii of Pd and H of 2.830 Å. Despite the possible rotations along the P2–C20 axis, a
substitution of the hydrogen ortho to the phosphine group with a fluorine atom, a methyl group or a methoxy group, could give us an indication of the influence of different blocking groups on the (co)polymerization outcome.
Figure 2.13. Two different views of the crystal structure of complex 2.14 at 30% thermal ellipsoids. Selected bond lengths (Å) and angles (deg) of 2.14: Pd1−P2 = 2.2559 (7); Pd1−C14 = 1.996 (3); Pd1−O6 = 2.156 (2); Pd1−N36 = 2.088 (3); P2−Pd1−N36 = 174.62 (8); C14−Pd1−O6 = 173.40 (10). 42 | Chapter 2
2.5.2. Synthesis of ligands and palladium complexes
The synthesis of the ligands (Scheme 2.10) was based on reported procedures.27 1 equiv. of
Ar-H or Ar-Br was reacted with 1.05 equiv. of n-BuLi at 0 °C (R2 = Me, OMe or OEt) or
– 78 °C (for R2 = F) in pentane or THF to give the corresponding aryl lithium (Ar-Li), which
then reacted with 0.5 equiv. of Cl2PNEt2 at –78 °C for 1 h before the mixture was warmed
up to ambient temperature and stirred for another hour. Addition of excess of HCl in diethyl
ether produced after cannula-filtration and solvent evaporation the chlorodiarylphosphine
product (Ar2PCl). A THF solution of Ar2PCl at –78 °C was transferred dropwise into a
Schlenk flask containing a freshly prepared solution of lithium (2-sulfonatophenyl)lithium
2.15 at –78 °C, and the resulting mixture was allowed to warm to room temperature and
stirred for 3-4 h before an acidic work up and isolation of the ligand. Coupling between the
phosphorus and the hydrogen was present in their respective 1H NMR spectra of the ligands
1 1 1 1.4b ( JPH = 573.8 Hz), 1.4d ( JPH = 601.0 Hz) and 1.4e ( JPH = 600.0 Hz). One should
therefore expect to find these ligands in their zwitterionic form in solution.
The palladium dimers complexes of type 2.16 in Scheme 2.10 were prepared by treating the acidic (P∼O)H ligand with an equivalent of PdMe2(TMEDA) at ambient temperature in
THF. The precipitated dimers were collected, dried and/or recrystallized, and directly used as homooligomerization catalysts.6 Single crystal X-ray structures of the dimeric complexes
2.16b and 2.16e were obtained and are presented in Figure 2.14 and Figure 2.15,
respectively. The structure of 2.16b showed one methyl group in the apical position of the
metal, as expected. The distance Pd81–H107 (2.720 Å) and Pd81–H109 (2.765 Å) were shorter
than the sum of their Van der Waals radii (2.830 Å). The X-ray structure of 2.16e showed that the ethoxy group replacing the ortho hydrogen H25 in complex 2.14 (Figure 2.13) was twisted out of the Pd coordination plane by roughly 40°. Though, O104 interacted with Pd95 as the distance Pd95–O104 (3.054 Å) was found to be slightly shorter than the sum of their
Van der Waals radii (3.150 Å).
Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 43
Figure 2.14. Crystal structure of complex 2.16b at 30% thermal ellipsoids. Residual solvents are omitted for clarity. Selected bond lengths (Å) and angles (deg) of 2.16b: Pd81−P83 = 2.2341 (11); Pd81−C89 = 2.034 (4); Pd81−O87 = 2.151 (3); Pd81−N69 = 2.195 (3); P83−Pd81−N69 = 172.62 (10); C89−Pd81−O87 = 178.37 (14).
Figure 2.15. Crystal structure of complex 2.16e at 30% thermal ellipsoids. Hydrogen atoms and some residual solvents are omitted for clarity. Selected bond lengths (Å) and angles (deg) of 2.16e: Pd95−P97 = 2.2384 (5); Pd95−C161 = 2.0080 (19); Pd95−O100 = 2.1879 (3); Pd95−N83 = 2.1812 (14); P97−Pd95−N83 = 173.50 (4); C161−Pd95−O100 = 173.75 (7).
44 | Chapter 2
The dimer 2.16c was poorly soluble in non-coordinating solvents (same observation for the
dimer 2.16a). Therefore, we prepared its corresponding pyridine-bound Pd complex 2.16c-
pyr by substituting the TMEDA bridge in 2.16c with pyridine. A doublet with a coupling
constant 32.2 Hz at δ –12.4 ppm was observed in the 31P NMR spectrum, whereas as the 19F
NMR revealed the presence of two non-equivalent fluorine atoms: one singlet at δ –100.6 ppm and a doublet with a coupling constant 32.2 Hz at δ –96.6 ppm, in a 1:1 ratio. We concluded
that this second fluorine atom coupled with the phosphorus atom and probably interacted
with the metal center. Our hypothesis was confirmed by the X-ray structure obtained after
recrystallization in the glovebox of 2.16c-pyr from DCM/Et2O (Figure 2.16). F2, one of the two fluorines, was located in the apical position of the metal center. The distance Pd1–F2 is
2.961 Å (sum of rw = 3.100 Å).
Figure 2.16. Crystal structure of complex 2.16c-pyr at 30% thermal ellipsoids. Hydrogen atoms and some residual solvents are omitted for clarity. Selected bond lengths (Å) and angles (deg) of 2.16c-pyr: Pd1−P1 = 2.2338 (8); Pd1−C26 = 2.025 (4); Pd1−O1 = 2.160 (2); Pd1−N1 = 2.115 (3); P1−Pd1−N1 = 173.06 (7); C26−Pd1−O1 = 175.31 (12).
Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 45
Scheme 2.10. Synthesis of (P∼O)H ligands and catalysts 2.16.
2.5.3. Homopolymerization of MA and ESI–MS analysis of the results
The reactions were performed in a sealed vial, in toluene and in the presence of excess MA.
The mixture of 2.5 mM of catalyst, toluene and MA was stirred at 60 °C for 16 h in the dark.
After the indicated time, a metallic deposit was observed in the vials. The oligomers were diluted in MeOH after the work up and electrosprayed with a source CID of 35 V. This 46 | Chapter 2 allowed the observation of sodium adducts of the oligomers and a qualitative study of the homooligomerization reaction (Figure 2.17 and 2.18).
A)
B)
Figure 2.17. ESI–MS spectra of the sodium adducts of MA-oligomers obtained from the homooligomerization using catalyst 2.16c in A) and 2.16d in B). Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 47
Figure 2.18. H-end and Me-end MA-oligomers distributions obtained from the ESI–MS spectra of the homooligomerization of MA with various catalysts.
Pentamers of MA were the most abundant oligomers obtained with the catalysts 2.16a,
2.16b and 2.16c, whereas, with 2.16d and 2.16e, oligomers with 10 to 11 consecutive MA were obtained as the major chains formed. The higher Me-end oligomers/H-end oligomers intensity ratio observed when catalyst 2.16c was used, in comparison to what was observed with 2.16a, for example, could be attributed to its low reactivity towards the olefin 48 | Chapter 2
coordination-insertion rather than to the reduction of the β-hydride elimination process. This
low reactivity toward polar olefins would favor the catalyst decomposition pathways.
Catalysts 2.16d and 2.16e, on the contrary, exhibited a better reactivity for the same
migratory-insertion. This result suggested that the electronic properties of the ligands, due
to the substitution of the hydrogen ortho to the phosphine, are more important than the
steric hindrance at the axial face of the metal center when it came to explain the results
obtained in the homopolymerization of MA. Electron-donating substituents increase the
electron density on the metal, thus favoring the coordination-insertion of polar olefins bearing
an electron-withdrawing group like MA, while reducing the occurrence of the agostic
interactions leading to the undesired β-hydride elimination. Similar observations were later
reported by Mecking and co-workers.28 However, attempts to reproduce the results reported
in the literature on the homopolymerization of MA using the DMSO-bound palladium
catalyst 1.5a29 (Scheme 2.1) were unsuccessful – the large amount of material obtained in
the literature was not reproduced in our hands. We encountered the same irreproducibility,
while attempting to reproduce the MA-homopolymerization using the catalyst prepared in
30 situ from 1 equiv. of (COD)PdMeCl and 1 equiv. of PPh3. One possible explanation of this irreproducibility was that in the reported homopolymerizations, the reaction conditions or the vessel favored the generation of radicals. In control reactions performed under reported conditions3 in the absence of Pd metal source and in the presence of an alkyl radical source,31
similar MA-homopolymerization results were obtained, despite the presence of the radical
quenchers BHT or Sumilizer WX-R from Sumitomo Chemical Co.. It has been reported that radical inhibitors can be inefficient, or that they slow down or shutdown a late transition metal based polymerization of alkenes.9,32,33 The free radical MA-polymerization was not
observed in the presence of Galvinoxyl. At the same time, comparable polymerization results
were obtained when the DMSO-bound (P∼O)Pd-based catalyst 1.5a (40 µmol) was used in
the polymerization of ethylene (5 bars) with or without Galvinoxyl (200 µmol): 3.43 grams
of polyethylene without and 3.26 grams with the radical trapping agent. Claims of
coordination-insertion mechanism governing the (co)polymerization of polar olefins such as Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 49
MA should be made with extreme caution as the existing radical tests can easily be
misleading.
2.6. Conclusions
In this work, we studied the nature and the reactivities of the palladium hydride species generated in situ and from which a fast and reversible equilibrium between Pd(II) and Pd(0) takes place, and was found to represent a key step for both the irreversible deactivation and for further improvement of the (co)polymerization activity. We showed that the polymerization catalysts could be rescued in situ in the presence of convenient electrophiles.
However, the regular occurrence of the β-hydride elimination process followed by the chain transfer step was found to be the main limitation for the application of the regeneration strategy. Efforts should be made to reduce the frequency of occurrence of this pathway.
One major issue was raised during our investigation after, firstly, the low improvement induced by the ligand design on the homopolymerization of MA and, secondly, the unsuccessful attempts to reproduce the results reported in the literature on the homopolymerization of MA. The reported MA homopolymerizations were suspected to be free radical-driven, even in the presence of BHT used to avoid the radical processes. This observation makes futile any further catalyst improvement for industrial application.
Investigations on the effects of radical traps, or the development of more reliable radical traps in the transition metals catalyzed (co)polymerization of polar olefins, are needed in order to rule out this undesired process in the (co)polymerization.
2.7. References
1 Boor, J., Jr., Ziegler-Natta Catalysts and Polymerizations; Academic Press: New York, 1979.
2 Goodall, B. L. Top. Organomet. Chem. 2009, 26, 159–178.
3 Guironnet, D.; Roesle, P.; Ruenzi, T.; Göttker-Schnetmann, I.; Mecking, S. J. Am. Chem.
Soc. 2009, 131, 422–423.
50 | Chapter 2
4 Vela, J.; Lief, G. R.; Shen, Z.; Jordan, R. F. Organometallics 2007, 26, 6624–6635.
5 Crabtree, R. H. Chem. Rev. 2015, 115, 127–150.
6 Water-induced irreversible deactivation of the catalysts have been proposed by Claverie and co-workers : Skupov, K. M.; Hobbs, J.; Marella, P.; Conner, D.; Golisz, S.; Goodall, B. L.;
Claverie, J. P. Macromolecules 2009, 42, 6953–6963.
7 A report of the catalysts deactivation pathways appeared in the literature late 2012: Rünzi,
T.; Tritschler, U.; Roesle, P.; Göttker-Schnetmann, I.; Möller, H. M.; Caporaso, L.; Poater,
A.; Cavallo, L.; Mecking, S. Organometallics 2012, 31, 8388–8406.
8 An acidity scale of some metal hydrides can be found in the following review: Morris, R.
H. Chem. Rev. 2016, 116, 8588–8654.
9 Nakamura, A.; Ito, S.; Nozaki, K. Chem. Rev. 2009, 109, 5215–5244.
10 Ma, Q.; Chakraborty, D.; Faglioni, F.; Muller, R. P.; Goddard, W. A.; Harris, T.;
Campbell, C.; Tang, Y. J. Phys. Chem. A 2006, 110, 2246–2252.
11 Pestovsky, O.; Shuff, A.; Bakac, A. Organometallics 2006, 25, 2894–2898.
12 Piche, L.; Daigle, J.-C.; Rehse, G.; Claverie, J. P. Chem. –Eur. J. 2012, 18, 3277–3285.
13 (a) Herrmann, W. A.; Brossmer, C.; Öfele, K.; Reisinger, C.-P.; Priermeier, T.; Beller, M.;
Fischer, H. Angew. Chem. Int. Ed. Engl. 1995, 34, 1844–1848; (b) Rezabal, E.; Asua, J.;
Ugalde, J. M. Organometallics 2015, 34, 373–380.
14 Bondi, A. J. Phys. Chem. 1964, 68, 441–451.
15 Wucher, P.; Caporaso, L.; Roesle, P.; Ragone, F.; Cavallo, L.; Mecking, S.; Göttker-
Schnetmann, I. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 8955–8959.
16 (a) Morita, D. K.; Stille, J. K.; Norton, J. R. J. Am. Chem. Soc. 1995, 117, 8576–8581;
(b) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc. 1997, 119, 12441–12453;
(c) Grushin, V. V. Organometallics 2000, 19, 1888–1900.
17 Espinet, P.; Albéniz, A. C., Fundamentals of Molecular Catalysis. Current Methods in
Inorganic Chemistry, vol. 3; ed. Yamamoto A. and Kurosawa H., Elsevier, Lausanne, 2003,
Phosphine Sulfonate Pd–Based Catalysts: From the Deactivation to the Regeneration in Situ | 51
ch. 6, pp. 293–371.
18 (a) Ozawa, F.; Ito, T.; Yamamoto, A. J. Am. Chem. Soc. 1980, 102, 6457–6463.; (b)
Kranenburg, M.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M. Eur. J. Inorg. Chem. 1998,
155–157.
19 Armentrout, P. B., Theory and Ion Chemistry, in Encyclopedia of Mass Spectrometry; M.
L. Gross and R. Caprioli, Editors, 2003, p. 426–436.
20 Batiste, L. M. J. Diss. ETH No. 21455, Ph.D. Dissertation, ETH Zürich, 2013.
21 Batiste, L. M. J.; Chen, P. J. Am. Chem. Soc. 2014, 136, 9296–9307.
22 Theofanis, P. L.; Goddard, W. A., III. Organometallics 2011, 30, 4941–4948.
23 The presence of traces amounts of HCl in the deuterated chlorinated solvent cannot be
ruled out and could also take part in the formation of the palladium chloride complex 2.13:
https://www.isotope.com/uploads/File/NMRUNpriced-proof.pdf.
24 Noda, S.; Nakamura, A.; Kochi, T.; Chung, L. W.; Morokuma, K.; Nozaki, K. J. Am.
Chem. Soc. 2009, 131, 14088–14100.
25 Bouffard, J.; Itami, K. Top. Curr. Chem. 2010, 292, 231–280.
26 For an excellent review about the application of this strategy on the diimine systems, see:
Camacho, D. H.; Guan, Z. Chem. Commun. 2010, 46, 7879–7893.
27 Hearley, A. K.; Nowack, R. J.; Rieger, B. Organometallics 2005, 24, 2755–2763.
28 Neuwald, B.; Falivene, L.; Caporaso, L.; Cavallo, L.; Mecking, S. Chem. Eur. J. 2013, 19,
17773–17788.
29 700 mg of polymeric material formed from the homopolymerization of 4 mol l–1 solution of
MA in toluene using 80 µmol of 1.5a after 4 h at 95 °C in the presence of BHT: see reference
3 for more details.
30 Sen, A.; Kacker, S.; Hennis, A.; Polley, D. J. Palladium (II) Catalyzed Polymerization of
Norbornene and Acrylates, U.S. Patent 6,111,041, August 29, 2000.
31 Arene diazonium salts in the presence of phosphines or pyridine and 4-nitrobenzyl 4-
nitrobenzenesulfonate were tested. For Arene diazonium salts and pyridine inducing radicals
52 | Chapter 2
formation, see: Abramovitch, R. A.; Saha, J. G. Tetrahedron 1965, 21, 3297–3303.
32 Albéniz, A. C.; Espinet, P.; López-Fernández, R.; Sen, A. J. Am. Chem. Soc. 2002, 124,
11278–11279.
33 Tian, G.; Boone, H. W.; Novak, B. M. Macromolecules 2001, 34, 7656–7663.
Chapter 3
Mechanistic Investigations of a Novel Electrophilic Pd–
Catalyzed Cyclopropanation of Norbornene
Dr. Mihai Raducan is greatly acknowledged for his discovery of the stable complex 3.12, which later permitted the development of a synthetic procedure for its isolation and characterization by X-ray diffraction.
3.1. Introduction
3.1.1. Motivations
Cyclopropane rings are found in a wide range of natural products and represent a versatile
and useful building blocks for the preparation of natural and synthetic products.1 They are
valuable structural units in the insecticide, 2 the flavor and fragrances, 3 and the
pharmaceutical industries. The three-membered ring occupies the 10th position of the 100
most frequently used ring systems in the 2012 U.S. FDA (Food and Drug Administration)
Orange Book drug database.4 Some examples of important cyclopropane-based molecules are
depicted in Figure 3.1.
Figure 3.1. Examples of important substances containing a cyclopropyl scaffold. 54 | Chapter 3
The widespread methods used to synthesize most of the cyclopropyl scaffolds from electron-
rich alkenes derive from the Simmons-Smith reaction,5 named after Howard E. Simmons and
Ronald D. Smith. The Simmons-Smith cyclopropanation reaction is an electrophilic cheletropic cycloaddition reaction between an olefinic double bond and an organozinc carbenoid reagent, formed during the reaction. It requires the use of an activated zinc metal, usually coupled with copper. The organozinc reagent is proposed to be the halomethylzinc
3.1. Other variations of the reaction use metals such as samarium,6 aluminum7 or lithium8 to form similar halomethylmetal carbenoids in situ.
Scheme 3.1. Representative cyclopropanation using Zn carbenoid.
The most notable advantage offered by this reaction is its stereospecificity with respect to
the geometry of the alkene bond. 9 Furthermore, the reaction has been utilized to
cyclopropanate various functionalized olefins with a preference for the less sterically hindered
and electron-rich ones. However, the stoichiometric or even more than stoichiometric
utilization of the Zn metal generates significant amounts of metal-containing waste.10 New strategies for the catalytic preparation of cyclopropanated compounds from various electron- rich alkenes are thus needed. The decomposition of diazocompounds presented in the first chapter of this thesis (Chapter 1) is not an alternative for industries due to the difficulties one would face with the scale-up of a reaction which uses highly explosive, toxic, volatile, and carcinogenic methylene donors such as diazomethane. 11 However, the Pd-catalyzed
decomposition of diazomethane followed by the carbopalladation of alkenes, and other Pd- Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 55
based cross-coupling reactions reported in the literature represent an excellent base for the
rational mechanistic design of a more efficient and flexible Pd-based catalytic cycle for the
synthesis of cyclopropanes from various electron-rich double bonds.
3.1.2. Design of a mechanistic Model
The knowledge gained from the different palladium-catalyzed cross-coupling reactions constituted a foundation to the development of the predictive mechanistic model in Scheme
3.2 that we decide to name “diverted Heck”.12
Scheme 3.2. Designed mechanistic model for the cyclopropanation of electron-rich olefins.
As described in the classical Heck reaction, the first step would be an oxidative addition of the electrophilic halide or pseudohalide species followed by the coordination-insertion step.
Here ends the similarity with the Heck reaction. However, as discussed in the introduction, the generated Pd-alkyl species 3.5 can undergo a β-hydride elimination process and β- dehydropalladation to release an alkene 3.8 like in the Heck reaction. The challenge of the model is to find a more competitive step that would lead to the palladacyclobutane 3.7 and would then undergo the reductive elimination, diverting the cycle to the cyclopropanes from the Heck cycle. We chose to have a transmetalation step to compete with the β-hydride 56 | Chapter 3
elimination under suitable conditions. To make it possible, the species undergoing the
oxidative addition should therefore be designed to possess both a nucleofuge (for the oxidative addition) and an electrofuge moiety (for the transmetalation). For this step, we opted for the transmetalation of boron to Pd(II), the same type of transmetalation one would find in the
Suzuki coupling. The targeted amphiphilic reagents are represented in Figure 3.2.
Figure 3.2. Targeted amphiphilic reagent used as methylene donor.
Potassium halomethyltrifluoroborate salts 3.10 and halomethylpinacol boronates 3.11
(Figure 3.3) are commercially available substrates possessing the essential features required in the mechanistic model for use in the design and optimization of a cyclopropanation procedure: an electrofuge and a nucleofuge side. They are relatively non-toxic, air-stable, and
thermally stable reagents. Halomethyltrifluoroborates are also moisture-stable and solid
crystalline and therefore easier to handle. Formation of stoichiometric boron waste represents
a negligible issue for most chemists, industries, and the environment, as generated water-
soluble boric acids are non-toxic13 and many cost effective boron recovery methods exist.14
Figure 3.3. Commercially available halomethylboron species.
Oxidative homocoupling of the boronic parts of two methylenating reagents is one of the
challenges to be expected during the reaction optimization. Strategies to minimize its Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 57
occurrence have been developed by Miller and coworkers15 and consist of a combination of
rigorous exclusion of oxygen and the use of a mild reducing agent such as potassium formate.
An oxygen-free procedure, in which 1.5 equiv. of iodomethylboron reagents reacted with 1.0 equiv. of NBE in the presence of K2CO3 and a catalytic amount of the Herrmann-Beller palladacycle (1.2) in DMF/H2O (8/1) (additional cesium fluoride was required in the case of
iodomethylboron 3.11a) and at 90 °C, was developed in our laboratories and found to be
very efficient in the cyclopropanation of norbornene (NBE) in excellent yields (Scheme 3.2).16
However, only little was known about the actual mechanism by which cyclopropanes are formed, though we did have our speculations.16 Herein, by means of experimental methods and density functional theory (DFT) calculations, we wish to investigate the mechanism of
the cyclopropanation of NBE and validate our “diverted-Heck” mechanistic proposal.
Scheme 3.2. Key results of the carbopalladation reactions of NBE to cyclopropanes using iodomethylboron species.
3.2. Oxidative addition of the amphiphilic reagents to Pd(0)
Oxidative addition of the electrophilic part of the methylenating reagents to an in situ-formed
Pd(0) intermediate is the first step in the proposed mechanistic model. It corresponds to the 58 | Chapter 3
oxidative addition of a Pd(0) on a C(sp3)–I bond which, unlike common alkyl halides, should give a more stable Pd(II) product due to the absence of β-hydrogens. Despite the measures taken to limit the homocoupling pathways, we were also particularly interested to know the order of priority in the reactivity of the two sides of the methylenating reagents with Pd(0).
3.2.1. Oxidative addition of ICH2BF3K to Pd(0)
Although the developed procedure is based on a Pd(II) as metal source, the cyclopropanation reaction of NBE has been shown to also proceed when a Pd(0) source was employed, instead.
Pd(0) must be formed in situ prior to the first step in the proposed mechanistic model.
Therefore, for our studies, we first decided to investigate the direct oxidative addition of
3.10a on a zero-valent Pd center. Oxidative addition of 3.10a to a “(o-tolyl)3PPd(0)” intermediate, reactive species in solution, when [(o-tolyl)3P]Pd(0) or the mixture of the ligand
(o-tol)3P (1.1a) and Pd(dba)2 is used at ambient temperature, was not observed by NMR or
ESI–MS, the reaction evidently requiring the higher temperatures. At higher temperatures,
decomposition to black palladium is observed. In contrast, spectroscopic observations (NMR
and ESI–MS) clearly show that a direct oxidative addition of 3.10a to an in situ-generated
Pd(0) complex stabilized by the ligand t-BuXPhos in DMF-d7 does occur at room
temperature.
Scheme 3.3. Synthesis of complexes 3.12.
The Pd(II) intermediates resulting from the oxidative addition of 3.10a (Scheme 3.3) would be natively uncharged in solution, meaning that electrospray ionization would require coordination of a proton or alkali-metal cation, with potentially increased complexity in the Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 59
spectrum and likely reduced intensity. The results of the gas phase experiments were indeed
in agreement with our predictions. In fact, when the THF solution of 3.12 was electrosprayed
in the positive mode, we observed a signal at m/z 651, which could be assigned as the
potassium adduct of the iodide-abstracted product of the oxidative addition of 3.10a (Figure
3.4). A quartet with a coupling constant of 32.1 Hz at δ 75.5 ppm was observed in the proton
decoupled 31P NMR spectrum in Figure 3.5. The observed quartet should arise from the
fluorine-phosphorus coupling. The stable palladium complex 3.12 was soluble in DCM and could be recrystallized in the presence of pentane, and characterized by X-ray single-crystal diffraction. It was isolated as the major component of a mixture containing 9H-carbazole (see
Scheme 3.3). The X-ray structure of 3.12 depicted in Figure 3.6, the first-formed intermediate in the proposed catalytic cycle, confirms the presence of a coordination to the Pd metal of one of the fluorides (2.1833 Å) attached to boron. A markedly small B1−C1−Pd1 angle
(93.17°) is therefore observed. Furthermore, the additional C2−Pd (2.400 Å) interaction leads to a Pd1−F1 bond sitting on top of the triisopropylbenzene group participating in the stabilization of the whole structure.
BF3 K tBu P Pd tBu iPr iPr iPr m/z 651
Figure 3.4. ESI mass spectrum of a solution containing the complex 3.12.
60 | Chapter 3
phine through Pd. ons and the phos lings between the methylene prot P HMBC spectrum showing the coup 31 H- 1 . Figure 3.5 Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 61
Figure 3.6. X-ray structure of complex 3.12 at 50% thermal ellipsoids. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg) of 8: Pd1−P1 = 2.2302(8); Pd1−C1 = 2.045(3); Pd1−F1 = 2.1833(17); Pd1−C2 = 2.400(3); B1−C1−Pd1 = 93.17(19); F1−Pd1−P1 = 167.56(5).
3.2.2. Oxidative addition of ICH2Bpin to Pd(0)
Unlike the methylene donor agent 3.10a, the methylene donor agent 3.11a reacts readily at
room temperature with “(o-tolyl)3PPd(0)” intermediate generated in situ in THF-d8. Two major phosphine-containing species were observed in the 31P NMR spectrum shown in Figure
3.7. The two broad singlets appeared at δ 32.2 and 31.2 ppm. These peaks are most likely signals of phosphine ligands in the cis and trans isomers of bridged, dinuclear Pd species 3.13 which would be formed after oxidative addition of Pd(0) to the C−I bond of ICH2Bpin. The formation of dimeric LRPd(μ-X)2PdRL species, and its order of stability relative to the halide, was presented in the first chapter of this thesis and shown to be favorable for iodide.
Unfortunately, the dimeric palladium complex decomposes slowly at ambient temperature to give mostly the peak of the P-C reductive elimination, making its isolation difficult. 62 | Chapter 3
Figure 3.7. 31P NMR spectrum of the mixture consisting of 1.05 equiv. of the ligand 1.1a,
1 equiv. of Pd(dba)2 and 2.5 equiv. of 3.11a at room temperature in THF-d8.
An advantage provided by the oxidative addition of 3.11a to Pd(0) over 3.10a is the resulting charged species one would be expected to obtain upon a replacement of the halide with a better coordinating ligand. Analysis of the NMR tube content using ESI–MS, sprayed after dilution with acetonitrile, permitted the observation of undesired products (m/z 319 and m/z 431) as well as intermediate 3.14 (m/z 592; Figure 3.8) as the main palladium- containing species in the positive mode. Acetonitrile cleaves the presumed bridged, dinuclear
Pd species to generate the observed mononuclear cationic palladium species. An additional small Pd-containing species assigned to the MeCN bound 3.14 complex (m/z 633) was also observed. This species would be disfavored by the hindrance of the phosphine ligand 1.1a.
Mass-selection of the signal at m/z 592 followed by CID at very low collision energy (10 V) fully released the coordinated acetonitrile ligand.
Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 63
Figure 3.8. Full ESI–MS spectrum of the acetonitrile solution of in situ-prepared 3.13.
These experiments confirm that the first step in the effective catalytic cycle is the oxidative
addition rather than the transmetalation of the methylenating reagents 3.10a and 3.11a. In
the presence of nucleophiles (solvents, fluorides) and K2CO3, as in the cyclopropanation
conditions, similar iodide substitution (or abstraction) from 3.13 should take place leading in the presence of NBE to the next expected step in the proposed catalytic cycle: the carbopalladation i.e. coordination-insertion of the double bond.
3.3. Carbopalladation of NBE and cyclopropane formation
The inner sphere mechanism which involved the coordination of the alkene on the Pd metal center during the Pd-catalyzed decomposition of diazomethane to cyclopropane was one of
the motivation of investigating Pd as metal catalyst in this novel cyclopropanation reaction.
When excess NBE were added to the mixture prepared earlier and consisting of Pd(dba)2,
ligand 1.1a and the methylenating reagent 3.11a, heated 10 min to 60 °C then diluted in
acetonitrile and electrosprayed in the gas phase, a new peak corresponding predominantly to
cationic palladium species of mass m/z 645 was observed (Figure 3.9). These palladium species
could correspond either to NBE-coordinated complexes 3.15 or NBE-inserted complexes 3.16. 64 | Chapter 3
The definite identification was made with the help of a CID experiment.
O O P O B O P Pd B Pd
m/z 645 m/z 645
O O P P B O O B Pd Pd
m/z 739 m/z 739
Figure 3.9. Full ESI–MS spectrum of the acetonitrile solution of a mixture of 3.13 and NBE heated at 60 °C for 10 min.
The cations were collided in the collision cell with argon at a pressure of 0.5 mTorr, and with a collision energy of 25 V to give predominantly a peak at m/z 551 corresponding to the release of NBE likely from the NBE-coordinated Pd complexes (Figure 3.10A). The CID spectrum is depicted in Figure 3.10. The release of NBE, which is also possible via retro
carbopalladation, is rather unlikely due to the lack of sterics constrains on the carbon (sp3)
attached to the inserted NBE in 3.16 that would favor this pathway.17 A small peak was also
observed in the CID spectrum at m/z 537 and corresponds to the release of
tricyclo(3.2.1.02,4)octane from the mass-selected signal m/z 645 (Figure 3.10B), although
collision-induced β-hydrocarbyl elimination from the insertion product would have been
possible, in principle. We had observed β-methyl elimination from cationic Pd(II) neopentyl
complexes in the gas phase,18 but this reaction, the microscopic reverse of a migratory
insertion, was competitive only in the case that a β-hydride elimination is strongly disfavored
or impossible, a β-hydride elimination being disfavored for NBE. The generation of the signal
m/z 537 would be consistent with intramolecular transmetalation from 3.16, followed by
reductive elimination of the cyclopropane product from a palladacyclobutane intermediate. Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 65
Intramolecular transmetalation in solution is presumably much accelerated by nucleophilic
addition to the boronic ester, converting it to an “ate” complex,19 but one may interpret the
CID experiment to mean that, even without nucleophilic assistance, the proposed
intramolecular transmetalation, and subsequent reductive elimination of the cyclopropane
product is a plausible reaction when nothing more facile intervenes. In solution, cyclopropane
formation via reductive elimination from proposed for in situ-generated 20 or isolated 21 palladacyclobutane intermediates (generally upon coordination of π-acceptor ligands), has already been reported in the literature. In silico evidence for the formation of a palladacyclobutane intermediate prior to the release of cyclopropane has also been proposed.22
DFT studies in the gas phase were performed in order to assess the feasibility of the last steps of the postulated mechanism, for which intermediates have not been observed experimentally, in the absence of nucleophiles one would have in solution.
66 | Chapter 3
Figure 3.10. CID on the cation m/z 645. Collision gas pressure: 0.5 mTorr, Collision Energy: 25 V (center-of-mass reference frame).
3.4. Theoretical Investigations of the Cyclopropanation of NBE
To investigate the reaction pathways predicted by the gas phase experiments in more detail, density functional theory (DFT) calculations were carried out in Gaussian 09.23 Geometry optimizations, tight optimizations and geometry convergence criteria in combination with the ultrafine integration grid (a pruned (99590) grid) were performed with the BP86 functional.24
The effective core potential Stuttgart/Dresden and associated basis set25 for Pd and the
Dunning 95 full double-ζ basis set26 with an additional set of Cartesian d or p polarization
functions, SDD(d,p) for main-group elements and for hydrogen atoms, respectively, were
used. Single-point energy evaluations were done at the M06-L/SDD(d,p) level of theory.
Benchmark studies have confirmed the excellent accuracy of M06-L density functional in
modelling main-group and transition-metal thermochemistry, kinetics, and noncovalent
interactions.27 The GEDIIS algorithm28 was employed throughout. Frequency calculations
were carried out at the same level of theory to confirm the nature of each stationary point,
which also afforded zero-point energy (ZPE) corrections. The vibrational mode of the single imaginary frequency of transition structures was confirmed to correspond to the desired Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 67
reaction coordinate. The DFT-computed reaction coordinate is shown in Figure 3.11. Figures
were generated with CLYview29 and GaussView 4.1.30
For these studies, the cationic π-complex A, in which NBE interacts with Pd through its
double bond and through an agostic interaction of one of the hydrogen atoms attached on its
bridging carbon, was chosen as the reference point. It corresponds to the Pd complex 3.15 observed in the mass spectrometry as the major Pd species at m/z 645. In the gas phase, the
π-complex A is found to be slightly more stable by 0.3 kcal/mol than its chelate analogue F having the alkene double bond cis to the phosphine. The calculations indicated that due to the required higher energy barrier relative to the ligand dissociation pathway (25.9 kcal/mol against 24.3 kcal/mol), the direct migratory insertion from the complex A, a tight process, is unlikely. Therefore, the migratory insertion must be initiated by a cis/trans the isomerization of A to B higher in energy. The π-complex intermediate B is stabilized by a weak agostic interaction between the ortho-tolyl hydrogen and the metal in which the hydrogen occupies the open coordination site on the metal center. The cis/trans isomerization is found to proceed with an activation energy of 13.4 kcal/mol and the final isomer is destabilized by the presence of a trans influence interaction between the phosphine and the alkyl group. This results in a lower relative migratory insertion energy barrier of 7.0 kcal/mol via the transition state TSB-
C. The migratory insertion of the alkyl moiety into the NBE double bond from both A and
B leads to the same stable intermediate C, located on the intrinsic reaction coordinate (IRC)
from the two transition states. The energy difference between the two transition states for
the migratory insertion TSA-C and TSB-C is about 18.9 kcal/mol. The cis/trans isomerization
barrier TSA-B appears to be higher than that of the consecutive migratory insertion TSA-C in the gas phase, thus increasing the probability of formation of complexes C. From A to the transition state TSA-C, we observed an elongation of the length of the Pd–P bond (from 2.391 ppm to 2.472 ppm), whereas the same bond is shortened from B (2.446 ppm) to TSB-C (2.395
ppm). NBE can also dissociate from the π-complex B resulting in Pd species H energetically
less stable than its analogue G. 68 | Chapter 3
vel. Values of the done in the gas phase. p)//M06L/SDD(d,p) le the calculations were 09 at the BP86/SDD(d, using Gaussian 298.15 K are zero-point energy corrected. All of 298.15 K are zero-point energy corrected. . DFT-computed reaction coordinate Figure 3.11 energies in kcal/mol at Mechanistic Investigations of a Novel Electrophilic Pd–Catalyzed Cyclopropanation of Norbornene | 69
2 The cationic O-chelate Pd(II) intermediate C possesses a dz orbital of the metal as the highest occupied molecular orbital (HOMO) and the lowest occupied molecular orbital (LUMO) is
2 2 composed of the dx – y of Pd (II) and the σ* orbitals of the alkyl ligand, as illustrated in
2 31 Figure 3.12. The filled dz orbital can then interact with the Lewis acidic boron center, inducing the intramolecular transmetalation step. At the theoretical level used in this study, the transmetalation process is found to proceed without a local minimum on the potential energy surface before the occurrence of the reductive elimination step and the activation barrier for the process should be lower than 37.0 kcal/mol. For comparison, the computed activation barrier for the transmetalation between a Pd(II) iodo-vinyl complex and vinylsilane in the absence of fluoride anions is 45.8 kcal/mol, and 25.2 kcal/mol when iodide is replaced by fluoride.32 Fluoride and hydroxide anions, present in solution under our reaction conditions are also known to accelerate this process in Suzuki cross-coupling reactions and are therefore expected to lower its activation barrier. The reductive elimination took place via a palladacyclobutane transition state TSC-D, as predicted by the “diverted-Heck” mechanistic model in Scheme 3.2. In the geometry of TSC-D, the boron metal sits in the axial position of the Pd center. As previously stated, the intramolecular transmetalation and the following reductive elimination may involve some of the nucleophilic species present in solution and can therefore be made more facile than in the gas phase. The release of the cyclopropane product from D is driven by another loose dissociation process, resulting in the observation in ESI–MS collision cell of the signal m/z 537.
HOMO LUMO
Figure 3.12. Computed frontier orbitals (isoval = 0.07) for the complex C. 70 | Chapter 3
3.5 Conclusions
The goal of this work was to investigate the mechanism of the novel Pd-catalyzed cyclopropanation of NBE using halomethyl boron as methylene transfer agent developed in our laboratories. The development of the reaction was based on a mechanistic model called
“diverted-Heck”. Our validation of the proposed diverted-Heck mechanism started with the observation and manipulation using NMR and mass spectrometry techniques, and the isolation of Pd intermediates formed by oxidative addition of iodomethylboron reagents, or
Pd species derived from them by substitution of the halide by MeCN. The occurrence of the carbopalladation step was established by (1) the observation of the NBE-Pd π-complex 3.15, and (2) the formation of tricyclo(3.2.1.02,4)octane, the corresponding cyclopropane product, after a CID experiment on the signal assigned to 3.15, meaning that the migratory insertion occurred. The formation of the cyclopropane also closes the proposed catalytic cycle in Scheme
3.2. DFT calculations at the BP86/SDD(d,p)//M06L/SDD(d,p) level were in good agreement with both our observations and the proposed palladacyclobutane presented in the diverted-
Heck catalytic cycle, which we proposed to be easily accessible under the cyclopropanation conditions via transmetalation.
Although the catalytic reaction has shown excellent results with NBE, its application to more challenging electron-rich olefins such as cyclooctene (COE) has proven to be more challenging12 and efforts should be made in optimizing the reactions conditions in order to benefit fully from the advantages offered by this mechanistic model.
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2008, 41, 157–167; (f) Cramer, C. J.; Gour, J. R.; Kinal, A.; Włoch, M.; Piecuch, P.; Moughal
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4239–4243.
28 Li, X. S.; Frisch, M. J. J. Chem. Theory Comput. 2006, 2, 835–839.
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Chapter 4
Pd–Catalyzed Electrophilic Cyclopropanation of Electron– rich Alkenes and Allylic Alcohols
Dr. Mihai Raducan is thanked for discussions on the proposed mechanism presented in Scheme 4.4.
4.1. Introduction
“Active catalysts typically have labile sites that are in principle much more sensitive to all the species present in the reaction medium as well as to the ambient conditions than is a stable
complex in solution.” Robert Crabtree1
The newly developed Pd-catalyzed methodology for the cyclopropanation of electron-rich
alkenes using iodomethylboron as methylenation reagents only works best when the olefin is
either norbornene (NBE) or its derivatives, which is similar for other recently developed Pd-
based cyclopropanation methods.2 The excellent reactivity of NBE in these reactions can be
attributed to its high ring strain3 (21.6 kcal mol–1) and to some extend to the pyramidalization
of its double bond, among other possible contributions.4 The relief of the ring strain in NBE upon coordination to palladium results in a better stabilization of the generated π-complex with respect to the one that is formed between palladium and other cyclic electron-rich alkenes, such as cyclooctene (COE). Although a full conversion and an excellent selectivity over the Heck product was obtained in the cyclopropanation of NBE using this method, only low conversion and a poor selectivity for the desired cyclopropanation products were observed 76 | Chapter 4
for other substrates (Scheme 4.1). The challenge herein is therefore to find suitable reaction
conditions that are able to accommodate a large variety of alkenes. The understanding of the mechanism of the reaction to the desired “diverted-Heck” product and the undesired Heck product as well as the mechanism of other relevant processes taking place in the catalysis will be crucial for the optimization of the reaction conditions and the expansion of the substrates scope. Minor modifications to the reactions conditions, such as the choice of the DMA/MeOH solvent system in place of DMF/H2O and the used of extra ligands, were already necessary
for the reported cyclopropanation of COE (scheme 4.1). We continued using COE as model substrate for this study as there was ample room for improvement in yield and selectivity.
Scheme 4.1. Cyclopropanation reaction of COE using the methylenating reagent 3.10a.
A general observation made in these cyclopropanation reactions is the formation of black deposit at the end of the reaction, which is an indicator for catalyst decomposition by aggregation. This decomposition has been shown to be accompanied by the formation of methyltri-o-tolylphosphonium salts as a result of a P–C reductive elimination, preceded or followed by a protodeboronation step.5 The formation of the phosphonium salt via P–C reductive elimination has been observed in cross-coupling reactions6 and polymerization7 where it was shown to be the first step in the aryl-aryl or aryl-alkyl exchange on the Pd metal center. It was demonstrated that the use of the (o-tolyl)3P ligand 1.1a resulted in the
formation of the lowest amount of phosphonium salts presumably due to the steric bulk Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 77
induced by the presence of the ortho methyl groups on the ligand aromatic system.6
The protodeboronation, on the other side, is a well-known side reaction in all Suzuki-type
cross-coupling reactions and involves in its mechanism the use of alcohols or water. Its
frequent occurrence in these reactions is the reason of the success of organotrifluoroborates
(R–BF3K) as reagents instead of organoboronic esters or more reactive organoboronic acids.
The slow hydrolysis or alcoholysis of organotrifluoroborates into the corresponding esters or
acids allows maintenance of the ratio of the concentration of the catalyst and the boronic
acid high enough to favor the transmetalation over the protodeboronation pathway.8
Furthermore, in our case, a slow carbopalladation step would enhance the occurrence of the protodeboronation, leading to low yields of the products and fast catalyst deactivation. In both the P–C reductive elimination and the protodeboronation, the nature of the solvents and the temperature play an important role. The two undesired processes are accelerated by hydrophilic and polar solvents as well as high temperatures. However, R–BF3K species
dissolve only in polar solvents such as DMF and DMA,9 limiting the choice of solvent to be
used in the reaction, and the Suzuki coupling, in particular the transmetalation and the
reductive elimination steps, are facilitated by the use of polar protic solvents, such as water
or alcohols.10 Furthermore, high temperatures are usually required for some Pd-based cross-
coupling reactions to proceed efficiently.11 However, at such temperatures, if the alkene does
not react readily with the metal, the rate of degradation of the electrophilic reagents and/or
the catalyst is likely to be higher than the rate of carbopalladation and transmetalation.
These first examples are there to illustrate the challenge we are expecting to face in the
optimization process of the cyclopropanation reaction. Above all, it appears that the
successful improvement of this cyclopropanation reaction, for alkenes other than NBE, will
look like a tricky balancing act between maintaining a high catalytic activity and obtaining
the desired products in good yields.
4.2. Optimization of the cyclopropanation reaction of COE
4.2.1. Early optimizations 78 | Chapter 4
In an early optimization stage using the solvent system DMA/MeOH in a 2/1 ratio, it rapidly
appeared that lowering the temperature to 75 °C in the presence of 5 mol% of the catalyst
1.2 and 15 mol% of extra (o-tolyl)3P (1.1a) ligand affords better yield of the cyclopropane
product and selectivity over the Heck product compared to 85 °C and 65 °C. Under these
conditions, the expected bicyclo[6.1.0]nonane (4.2a) product was prepared in 54% yield from
COE (4.1a), a satisfactory mass balance being obtained with the balance of the material
being accounted for by the side product methylenecyclooctane (4.3a) and recovered starting
material. Increasing the amount of K2CO3 results in an increase in the selectivity for the
cyclopropane as illustrated by the entries 1, 2 and 3. β-Hydride elimination as well as the
deactivation of the Pd-based catalysts are often more strongly temperature-dependent1,12 than
other elementary steps in the catalytic cycle, in particular, migratory insertion or catalyst activation. Systematic reduction in the temperature for the Pd-catalyzed cyclopropanation slowed the overall reaction, but also selectively suppressed the terminal methylene side product, improving the ratio of “diverted Heck” to normal Heck (entries 3, 4 and 5). This
early optimization also permits confirmation of the importance of having an alcohol in the
reaction media, as reactions performed in DMA only yielded no product, whereas when using
only MeOH, 25% conversion of COE to cyclopropane is obtained. It also showed the
importance of the presence of DMA, probably related to the better solubility of reagents and
catalysts in this solvent. However, replacing MeOH with EtOH (entry 8) led to the rapid
degradation of the catalyst as black deposit was readily formed in the reaction vessel at 75 °C.
The origin of the behavior of the catalyst in the presence of EtOH could be attributed to a worse solubility of active Pd intermediates when EtOH is used, to a lesser efficiency in the alcoholysis of the methylenating agent 3.10a due to sterics, or to an easier decomposition of the catalyst via β-hydride elimination from a putative alkoxo-palladium intermediate formed with EtOH.13 Alkoxo-palladium intermediates are often proposed intermediates in Suzuki
cross-couplings formed after the displacement of the halide ligand in solution.14
Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 79
Table 4.1. Results of the initial optimization of the cyclopropanation reaction of COE.
No. Solvents (ratio) X 4.2a [%]a 4.3a [%]a Rem. 4.1a [%]a Total [%]a (4.2a/4.3a)
1 DMA/MeOH (2/1) 1.2 54.3 3.3 42.8 100.3 16.7
2 DMA/MeOH (2/1) 2.0 53.6 1.6 43.7 99.0 33.1
3 DMA/MeOH (2/1) 3.0 63.6 0.8 38.7 103.0 83.0
4b DMA/MeOH (2/1) 3.0 52.5 0.4 50.3 103.2 136.6
5c DMA/MeOH (2/1) 3.0 56.2 2.1 44.1 102.3 26.8
6 MeOH (1.6 ml) 3.0 25.4 0 75.5 100.9 –
7 DMA (1.6 ml) 3.0 0 0.8 100.1 101.0 0
8 DMA/EtOH (2/1) 3.0 3.1 0.5 90.9 94.4 6.9 aYields were evaluated by GC-FID. bReaction done at 65 °C. cReaction done at 85 °C. 4.1a*: 0.117 mmol.
An additional optimization focused on the catalyst used in the reaction (Table 4.2). Utilizing
the [(o-tolyl)3P]2PdCl2 catalyst 4.4a led to a better conversion of COE to bicyclo[6.1.0]nonane
in 76% yield, with the selectivity for the cyclopropane of 73/1 (entry 1). This selectivity was increased to 148/1 by the addition of two additional equivalents of K2CO3 (entry 2). There
is a clear indication from this set of experiments about the importance of MeOH and K2CO3 in inducing high selectivities of the reaction for the “diverted-Heck” pathway. Interestingly, substituting CH3OH with CD3OD appeared to give an even better results (entry 3), although
it is not clear if the putative isotope effect exceeds the range of variation in the experiment.
However, considering the possible origin of the behavior observed when ethanol is used instead
of methanol, the co-solvent-induced catalyst decomposition hypothesis seems more plausible 80 | Chapter 4
given that β-hydride elimination would be made difficult from the deuterated methanol in comparison to the non-deuterated methanol.
Table 4.2. Introduction of the catalyst 4.4a to the cyclopropanation of COE.
No. X 4.2a [%]a 4.3a [%]a Rem. 4.1a [%]a Total [%]a Ratio 4.2a/4.3a
1 3.0 76.0 1.0 26.7 103.7 73.0
2 5.0 76.5 0.5 24.5 101.5 147.9
3b 5.0 82.9 0.6 18.4 101.8 135.4
aYields were evaluated by GC-FID. bDeuterated solvents used. 4.1a*: 0.117 mmol.
4.2.2. Ethylene Glycol (EG) as co-solvent and further optimizations
The observation that by simply exchanging the co-solvent MeOH with EtOH drastically reduced the yield of cyclopropane from 64% to 0% made us look at different co-solvents for the reaction. Unlike in the case of EtOH, the expected product and byproducts were obtained when EG was used. The first test reaction was done with a ratio of solvent of 8/1. 86% conversion of COE was obtained (see Table 4.3) with 84% yield of 4.2a formed, contrasting with the results obtained with EtOH. We anticipated that the presence of a second hydroxyl group in the structure of EG would play a crucial role in this catalysis. We thus decided to screen the ratio of the two solvents in the reaction mixture whose the results are presented in the Table 4.3 below. The optimum results were obtained with the solvent ratio DMA/EG of 16/1. 94% of 4.2a were then produced for only 2% of the Heck product 4.3a (entry 3).
Further decrease of the volume of EG affords a lower COE conversion (entry 5). Degradation Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 81
of the catalysts occurred at the end of the indicated reaction time with release of the free
ligand, observed in the 31P NMR. Running the reaction in the absence of COE did not result
in a similar degradation of the catalyst at the end of the reaction. The final reaction mixture
was orange. The 31P NMR spectrum in Figure 4.1 shows the signal of the free ligand 1.1a
(δ –30.4 ppm) and two small broad peaks at δ 35.6 ppm and δ 40.4 ppm which may correspond
to cis and trans isomers of a bridged, dinuclear Pd(II) species. The 11B NMR spectrum
contained four major peaks, one broad singlet at δ –0.99 corresponding to BF4–, one quartet
at δ 2.6 ppm and two other broad singlets at δ 7.0 ppm and δ 10.5 ppm (Figure 4.2). The
quartet signal corresponds to the starting ICH2BF3K. The two broad singlets are assigned to
the potassium bis(ethylene glycolato)borate having bound EG exchanging in solution with
free EG and/or fluoride. A signal at m/z –131 was also observed in the negative mode of the
ESI–MS. ESI–MS analysis of a reaction mixture, prepared analogously to the NMR samples,
allowed the detection, in the positive mode, of a peak at m/z 595 that is assigned as the cationic palladium intermediate 4.5, whose collision-induced dissociation (CID) is shown in
Figure 4.3. The structure in the inset represents the composition and makes no claim about whether the EG is bound monodentate or bidentate. The observation of the intermediates 4.5 clearly indicates that alcoholysis of the trifluoroborate is an important process taking place during the reaction. Some assisted version of this reaction may proceed in solution in the final step in the catalytic cycle. The tetracoordinate borate ester is the expected product.
Table 4.3. Screening of DMA/Ethylene glycol ratio.
No. DMA:EG (ratio) 4.2a [%]a 4.3a [%]a Rem. 4.1a[%]a Total [%]a (4.2a/4.3a)
1 8:1 83.8 3.0 14.4 101.3 27.6
2 10:1 89.4 2.1 9.1 100.6 43.0
3 16:1 93.6 2.3 7.1 103.0 40.5
4 20:1 93.6 2.4 7.5 103.5 38.3
5 32:1 86.5 2.2 12.1 100.8 39.2 aYields were evaluated by GC-FID. 4.1a*: 0.117 mmol. 82 | Chapter 4
Figure 4.1. 31P NMR spectra showing the products of the control experiment in the absence of COE.
Figure 4.2. 11B NMR spectra showing the products of the control experiment in the absence of COE.
Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 83
Figure 4.3. CID on cation m/z 595. Collision gas pressure: 0.5 mTorr, Collision Energy: 20 V (center-of-mass reference frame).
4.2.3. Screening of diols and triol co-solvents
Encouraged by the results obtained with EG, we looked at the effects of different diols and a
triol in the reaction. Instead of using the ratio of co-solvents, we opted for the use of the
equivalence of diols/triols in a constant amount of DMA. The results are reported in Table
4.4. The best performance is observed with EG. Increasing the number of methyl groups on
the EG backbone lowers the yield of the cyclopropane product from 69% with 1,2-propanediol
(entry 2, only one methyl group) to 0% with pinacol (entry 7), even in the presence of MeOH
used to generate Pd(0) in situ (entry 8). Cyclic 1,2-diols perform better than disubstituted
linear diols (entries 5 and 6 compared to entry 4), reinforcing the hypothesis of the alcohol
solvent-induced decomposition of the catalyst to explain the performance of 1,2-diols. One could imagine the EG chelating the metal thus rendering the β-hydrogens inaccessible for a 84 | Chapter 4
1,2-elimination on Pd. Glycerol, the only triol tested gave good results with 72% formation
of the cyclopropane (entry 3), whereas no cyclopropane was observed with catechol (entry 9),
despite the absence of β-hydrogens. The most plausible explanation for the poor performance
observed with catechol is the low nucleophilicity of the phenolate groups.15
Table 4.4. Screening of some diols and a triol.
No. Diols or Triol 4.2a [%]a 4.3a [%]a Rem. 4.1a [%]a Total [%]a (4.2a/4.3a)
1 EG 93.6 2.3 7.1 103.0 40.5
2 1,2-propanediol 68.9 1.8 32.1 102.8 39.3
3 glycerol 71.9 5.6 24.1 101.2 13.7
4 2,3 butanediol 5.6 1.6 91.9 99.0 3.6
5 cis-1,2-cyclohexanediol 54.4 3.9 39.1 97.5 13.8
6 trans-1,2-cyclohexanediol 59.0 10.2 28.5 98.0 5.8
7 pinacol 0.3 0.9 95.7 97.0 0.4
8 pinacolb 0.4 1.1 98.3 99.8 0.4
9 catechol 0.3 2.0 92.3 94.6 0.2
10 1,3-propanediol 4.2 0.5 96.7 101.4 8.8
11 2,4-pentanediol 0.2 0.4 94.6 95.3 0.4
aYields were evaluated by GC–FID. bIn the presence of 2 equiv. of MeOH. 4.1a*: 0.117 mmol.
4.2.4. Screening of the o-tolyl-based catalysts
Investigations on the ligands/catalysts capable to cyclopropanate NBE pointed into the
3 direction of ligands able to do a C(sp )–H activation, such as (o-tolyl)3P (1.1a) and (t-Bu)3P, Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 85
or catalysts based on them.16 Moreover, in the end of a cyclopropanation reaction of COE in
DMA/MeOH (2/1) and DMA-d9/CD3OD (2/1), the work-up solutions were electrosprayed in
the ESI–MS. The signal assigned to methyltri-o-tolylphosphonium (m/z 319) was not present in the solution of the reaction performed in deuterated solvents (see Figure 4.4). A peak, that
we assigned to be a distribution of deuterated C(sp3)–H of the methyltri-o-tolylphosphonium cation, was present. Alone, this result does not prove that the resulting cyclopalladated species is on the reaction coordinate, but shows that the cyclometalation of the ligand 1.1a takes place under the reaction conditions. For this reason, we screened a series of phosphine ligands bearing an o-tolyl and a t-butyl substituents (Figure 4.5). The results are reported in
Table 4.5. All cyclopropanation reactions were stopped after 22 h. The electronic influence of the para-substituted (o-tolyl) is shown in entries 1 through to 4. Only little influence is observed when the para substituents are F (σp (Hammett constant) = +0.062, 4.4b) and Me
(σp = –0.170, 4.4c), compared to the original ligand H (σp = 0, 4.4a). However, the electronic
effect is more pronounced with the substituent CF3 (σp = +0.540, 4.4d). Black palladium was present after ∼30 min of reaction when using these catalysts, whereas, in the case of 4.4c,
no catalyst decomposition was observed at the end of the reaction.
P H3C
m/z 319
Figure 4.4. Observed mass distribution of the different isotopologues of the methyltri-o- tolylphosphonium cation present in traces at the end of the reaction in MeOH (black line) and MeOH-d4 (blue line). 86 | Chapter 4
The ligand 4.6, which contains an electron-deficient olefin and is known to accelerate the reductive elimination,17 failed to reproduce the results obtained with 4.4a (entry 5). No
cyclopropane was produced. The decomposition of the ligand under our reaction conditions
might be the reason of this poor reactivity. The Pd catalyst 4.7 showed extremely poor
catalytic activity in this reaction (entry 6), contrary to 4.8a, which gave up to 35% yield of
cyclopropane (entry 7). We attribute this difference to the binding modes favored in the two
cases. The bidentate ligand in 4.7 would coordinate to the metal via a κ2-P,P-coordination
mode, whereas in 4.8a it can either adopt the κ1-P (bound by only one phosphine) or κ2-P,P-
coordination modes due to steric hindrance. The κ1-P-coordination mode has been observed
18 in the case of the ferrocenyl ligand found in 4.8b, of similar cone angle (from their PR3 ligand, 194°) and similar bite angle (104.20° for 4.8b19 and 104.03° for 4.8a determined from
its X-ray crystal structure from CHCl3/pentane, see Appendix A for details). The cyclopropanation of COE was doubly improved with the ferrocenyl catalyst 4.8b. 70% of
4.2a were then obtained (entry 8). Its monophosphine analogue gave a slightly lower yield of product (entry 9). In all these three last cases, the ratio of formation of 4.2a over 4.3a were in the same range. In accordance with previous reports, the in situ-generated catalyst gave a
lower yield compared to the well-defined one (entry 10). The importance of an additional
ligand is shown by the reaction employing a palladium source/ligand ratio of 1/1 (entry 11).
Lower conversion of COE was then obtained. The use of the n-butyldi-o-tolylphosphine ligand
4.10, with significantly increased donating ability, only produced 25% of bicyclo[6.1.0]nonane
with a similar selectivity as 1.1a (entry 12). o-Tolyldibenzophosphole ligand 4.11 treated
with the Pd source [COD]PdCl2 in a 2/1 ratio (entry 13) only gave 1.5% of 4.2a with
decomposition of the catalyst observed after 10 min. 4.11 was used as a ligand in order to
benefit from the reduced steric crowding compared to 1.1a. We expected the electronic
properties to be close to those of 1.1a.20 4.11 should however be less electron-donating than
1.1a. We attributed the fast decomposition of the catalyst to the easier associative
displacement of the phosphine by the olefin in solution generating a less stabilized Pd(II) Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 87
intermediate. The use of 30 mol% ligand (entry 14) retarded the catalyst deactivation (after
5 h, no deactivation but a decomposition was observed at the end of the reaction time) with no cyclopropane formed at the end of the reaction. The amount of toluene, observed by GC–
FID, suggests a decomposition of the ligand via P-C reductive elimination on Pd. We only obtained a very low conversion of COE into cyclopropane (20% yield) with the cage phosphine ligand 4.12 of complete opposite steric properties (entry 15). The ligand 4.12 is expected to be less electron-donating than 1.1a due to the presence of electron-withdrawing oxygens α to the phosphorus atom, despite the addition of a methoxy substituent at the para position of the o-tolyl group. Black deposit was not observed at the end of the reaction. The activity of the catalysts based on the ligands 4.11 and 4.12 may also suffer from the presence of only one o-tolyl group.
Figure 4.5. o-Tolyl- and t-butyl-based ligand and complexes studied. 88 | Chapter 4
Table 4.5. Screening of o-tolyl- and t-butyl-based ligands.
b No. Catalysts 4.2ab 4.3ab Rem. Total (4.2a/4.3a) b 1 4.4a 93.6 2.3 7.1 103.0 40.5
2 4.4b 90.8 2.3 7.8 100.9 39.4
3 4.4c 96.7 2.3 4.8 103.8 42.3
4 4.4d 13.1 0 91.9 105.0 –
5 4.6/[COD]PdCl2 (2/1) 0.4 0 100.4 100.8 –
6 4.7 2.3 0 98.3 100.6 –
7 4.8a 34.7 0.8 63.0 98.5 43.7
8 4.8b 70.1 2.0 24.5 96.6 34.9
9 4.9 53.7 1.2 45.8 100.8 43.7
10 1.1a/[COD]PdCl2 (1/1) 71.6 1.7 25.63 98.9 42.9
11 1.1a/[COD]PdCl2 (2/1) 85.5 2.1 11.3 98.8 40.9
12 4.10/[COD]PdCl2 (2/1) 24.6 0.6 70.1 95.2 42.5
13 4.11/[COD]PdCl2 (2/1) 1.5 0 97.7 99.2 –
14 4.11/[COD]PdCl2 (6/1) 0 0 98.2 98.2 –
15 4.12/[COD]PdCl2 (2/1) 19.7 0 76.7 96.4 –
a Standard conditions: 0.117 mmol (1.0 equiv.) of alkene 4.1a, ICH2BF3K (34.8 mg, 1.2 equiv.), K2CO3 (80.9 mg, 5.0 equiv.), Pd catalyst (5 mol%), solvents: DMA/EG (1.6 ml/0.1 ml, 16/1). bYields were evaluated by GC–FID. c44 h instead of 22 h. bYields in percentage were evaluated by GC–FID.
4.2.5. Additional optimization experiments
Table 4.6 summarizes the results of additional optimization of the cyclopropanation of COE.
Substituting THF for DMA led to a reduced conversion of COE (entry 1). While THF turned Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 89
out to be inferior to DMA as a solvent for the cyclopropanation, THF was the NMR solvent
of choice, though, and the reason why the investigations presented in Chapter 3 were done
in this solvent. Only 44% of cyclopropane 4.2a was formed when we substituted K2CO3 with
Cs2CO3. The yield also dropped to 81% when exactly 1.0 equiv. of ICH2BF3K was utilized
(entry 3). Use of BrCH2BF3K as the methylenating agent resulted in a full recovery of the
starting material (entry 4). Reducing the amount of catalyst to 1 mol% decreased the yield
of the cyclopropane to 71% (entry 5). The addition of 1 mol% extra ligand to the latter
improved the catalytic coupling (entry 6). A TON of ∼150 is reached after running the reaction for 44 h in the presence of 2.5 mol% of extra ligand (entry 7). Interestingly, lowering the
temperature to 65 °C for an extended reaction time (36 h) slightly increased the yield of
formation of the product 4.2a to 96% (entry 6).
Table 4.6. Additional optimizations.
4.4a (5 mol%)
K2CO3 (5.0 equiv.) + I BF3K + DMA/EG (16/1) (1.0 equiv.) (1.2 equiv.) 75 °C, 22 h 4.1a"standard conditions"a 4.2a 4.3a
No. Variations from "standard conditions" 4.2ab 4.3ab Rem. 4.1ab Totalb
1 THF instead of DMA 12.9 0.4 89.7 103.1
2 Cs2CO3 instead of K2CO3 44.0 1.9 51.7 103.1
3 ICH2BF3K (1.0 equiv.) 81.7 1.7 20.4 103.8
4 BrCH2BF3K 0 0 103.5 103.5
5 4.4a (1 mol%) 71.2 1.7 31.1 103.9
6 4.4a (1 mol%) + 1.1a (1 mol%) 86.1 2.1 14.5 102.8
7c 4.4a (0.5 mol%) + 1.1a (2.5 mol%) 74.0 2.1 26.0 102.2
8 65 °C for 36 h 96.2 2.6 3.1 101.9
a Standard conditions: 0.117 mmol (1.0 equiv.) of alkene 4.1a, ICH2BF3K (34.8 mg, 1.2 equiv.), K2CO3 (80.9 mg, 5.0 equiv.), 4.4a (4.6 mg, 5 mol%), solvents: DMA/EG (1.6 ml/0.1 ml, 16/1). bYields in percentage were evaluated by GC–FID. c44 h instead of 22 h. 90 | Chapter 4
4.3. Kinetic studies of the cyclopropanation of COE
To assess the rate law of the reaction, kinetic investigations were conducted. We initially
envisioned to monitor the kinetics of consumption of COE and formation of the products of
cyclopropanation reaction by 1H NMR spectroscopy, as well as the consumption of the
methylenating agent by 11B NMR spectroscopy. For this, the mixture of 1.0 equiv. of COE,
1.2 equiv. of ICH2BF3K and 5 equiv. of K2CO3 catalyzed by 5 mol% of the catalyst 4.4a in
DMA-d9/EG-d6 (16/1) was charged in an NMR-tube and the spectra were recorded over time at 75 °C for 16 h. Figure 4.7 shows the results of the 1H NMR monitoring cyclopropanation.
The peaks of the free ligand 1.1a were present at the end of the experiment in the proton
NMR (Figure 4.7) and also in the phosphorus NMR. In the 11B NMR spectra, we noted the
absence of a signal in the region of the spectrum where signals of trivalent boron should be
present (δ 20–40 ppm,21 Figure 4.8). However, these NMR studies were hampered by the poor
solubility of K2CO3 due to the lack of stirring in the tube. Consequently, the cyclopropane was produced in only 60% yield, leading us to conduct our investigations using a different technique.
ligand 1.1a
1 Figure 4.7. Stacked H NMR spectra (DMA-d9/EG-d6 (16/1)) of the cyclopropanation reaction of COE recorded at 75 °C. Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 91
Isotope pattern m/z –131 100
80
60
40
20
Relative Intensities Relative 0 128 129 130 131 132 133 134 135 m/z
Figure 4.8. 11B NMR spectrum of the methylenation reaction of COE recorded at 75 °C and isotope pattern of the bis(ethylene glycolato)borate anion in the ESI–MS.
Using the “different excess” protocol of Reaction Progress Kinetic Analysis (RPKA) developed
by Blackmond,22 the data obtained from the given methylenation reaction conditions and for two different known concentrations of the reagent of interest were analyzed. The consumption of COE was followed over time and yields were obtained by GC–FID. The overall reaction displayed zero-order kinetics with respect to ICH2BF3K and COE (Figure 4.9 and Figure
4.10, respectively). In these two cases, the kinetic profiles overlap until the catalyst starts to deactivate. The deactivation starts earlier in the presence of 1.0 equiv. of the methylenating reagent compared to when 1.2 equiv. of the reagent is utilized. However, we observed the
catalyst to deactivate earlier when 1.2 equiv. of COE is used in the reaction compared to the
reaction utilizing 1.0 equiv. A reaction order of 0.5 and –0.5 with respect to Pd and EG,
respectively were also observed (see Figure 4.11 and Figure 4.12). The influence of the
phosphine ligand on the initial reaction rate was found to be negligible (Figure 4.13). These
results suggest a turnover-limiting cleavage of a dinuclear Pd(II) species, the resting state in
the catalytic cycle, to a kinetically competent monomeric species.
92 | Chapter 4
0.07
1.0 eq. ICH2BF3K 0.06 1.2 eq. ICH2BF3K
0.05
0.04
0.03
0.02 concentration COE [M] COE concentration
0.01
0.00 50 100 150 200 250 300 350 400 time [min]
Figure 4.9. Influence of the methylenating agent on the rate of the reaction.
0.07 1.0 eq. COE 0.06 1.2 eq. COE
0.05
0.04
0.03
0.02 concentration COE [M]
0.01
0.00 50 100 150 200 250 300 350 400 time [min]
Figure 4.10. Influence of COE on the rate of the reaction. Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 93
5 mol% catalyst 5 mol% catalyst 10 mol% catalyst 0.07 10 mol% catalyst 0.07
0.06 0.06 0.05
0.05 2 0.04 R =0.986 -4 -1
concentration COE [M] k1=(2.45 ± 0.15).10 M min
k =(3.47 ± 0.16).10-4 M min-1 0.03 2 0.04 R2=0.994
0 20406080100120 0.03 time [min]
concentration COE [M] 0.02
0.01
0 50 100 150 200 250 300 350 400 time [min]
Figure 4.11. Influence of the catalyst loading on the rate of the reaction. Doubling the catalyst loading increases the initial rate of the reaction by 1.416.
DMA:EG (16:1) 0.075 0.08 DMA:EG (16:1) DMA:EG (16:0.5) 0.070 DMA:EG (16:0.5)
0.065 0.07 0.060
0.055 0.06 0.050
0.05 concentration COE[M] 0.045 -4 -1 k =(2.45 ± 0.15).10 M min 2 0.040 1 2 R =0.986 -4 -1 R =0.990 k2=(3.55 ± 0.21).10 M min 0.04 0.035 0 20406080100120 time [min] concentration COE [M] 0.03
0.02
0.01 0 50 100 150 200 250 300 350 400 time [min]
Figure 4.12. Influence of the co-solvent on the rate of the reaction. Two-fold reduction in the volume of the EG increases the initial rate of the reaction by 1.44. 94 | Chapter 4
0.070
0.065 P:Pd (1:1) P:Pd (2:1) 0.060
0.055
0.050
0.045 R2=1.000 2 concentration COE [M] COE concentration 0.040 R =0.970
-4 -1 0.035 k1=(3.10 ± 0.33).10 M min -4 -1 k2=(2.96 ± 0.33).10 M min 0.030 0 20406080100 time [min]
Figure 4.13. Influence of the phosphine concentration on the initial reaction rate: Negligible difference.
4.4. Substrates scope and limitations
Having optimized the reaction conditions, the scope of this transformation was explored with various unactivated olefins and allylic alcohols, leading to the main products which were determined to have the same stereochemical configuration as those produced by a control
Simmons-Smith-type cyclopropanation. The products were obtained in moderate to excellent yields, an exception being camphene (4.1l) for which only the starting material was recovered at the end of the reaction (Scheme 4.2). In general, the mass balance in these cyclopropanations was good, with the material not accounted for as cyclopropane consisting of the starting materials and/or β-hydride elimination products. GC–FID yields with detector calibration using independently synthesized reference compounds are listed; selected substrates were cyclopropanated on the mmole, i.e. gram, scale, for which the isolated yields are given in parentheses in Scheme 4.2. Under the given reaction conditions, α-pinene, isolated in only 12% yield following the Simmons-Smith procedure,23 gave up to 64% GC yield of the cyclopropane 4.2d. It is noteworthy that only one stereoisomer was obtained in this case, which was confirmed to be the diastereomer 4.2d through nuclear Overhauser effect spectroscopy (NOESY) experiments (Figure 4.14). Although the reaction is stereospecific, a significant difference in selectivity and reactivity is observed between (E) and (Z)-2-hexenol Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 95
(73:1 dr and 22:1 dr, respectively). Mostly the trans-cyclododecene (4.1k, 2:1, trans:cis in the commercial mixture used) is converted into the cyclopropane 4.2k. The tricyclic ketone
4.2m was prepared in good yield as a 7:1 mixture of its two isomers. The less abundant
isomer corresponds to the one having its cyclopropane protons close to the carbonyl, leading
to a downfield shift of δ 0.62 ppm. The cyclopropanation reaction of oxabenzonorbornadiene
(4.1n), which does not cyclopropanate under Simmons-Smith conditions at all,24 led specifically to the exo-isomer 4.2n in only 29% GC yield despite the complete consumption of the starting alkene. The qualitative order of reactivity for the different olefins (norbornene
> cycloheptene > cyclooctene > cyclohexene) in the preparative reactions seems to follow their propensity to form π-complexes.25 This suggests, of course, that ESI–MS observation of
the adducts with olefins less coordinating than norbornene might be difficult, which
corresponds, in fact, with our experience.
Figure 4.14. NOESY experiment of the independently prepared cyclopropane of α-pinene
(4.2d). 96 | Chapter 4
a Standard conditions: 0.117 mmol (1.0 equiv.) of alkene 4.1, ICH2BF3K (34.8 mg, 1.2 equiv.), K2CO3 (80.9 mg, 5.0 equiv.), 4.4a (4.6 mg, 5 mol%), solvents: DMA/EG (1.6 ml/0.1 ml, 16/1). bYields were evaluated by c d e GC–FID. 1.5 equiv. of ICH2BF3K used. Isolated yields in brackets (5.85 mmol of alkene 4.1 used). In the presence of extra 1.1a (5 mol%). fCommercial mixture of cis and trans (2:1, trans:cis). Scheme 4.2. Pd-catalyzed methylenation reaction: scope of the alkenes and allylic alcohols. Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 97
Methylenation reaction of 5-decene
A discrimination in the methylenation reaction of the isomers of 5-decene is observed
(Scheme 4.3). At the same reaction conditions, trans-5-decene (4.1s) and cis-5-decene (4.1t) were converted into the corresponding cyclopropane in 75% and 13% yields, respectively.
Furthermore, the cyclopropane 4.2s was formed in 62% yield, >99:1 dr with an observed deposit of a metallic black palladium, while 4.2t was obtained in 9% yield, 12:1 dr with no similar catalyst aggregation and deposition observed. Moreover, the slower rate of cyclopropanation observed in the case of cis-5-decene with respect to that of trans-5-decene seems to arise from the steric hindrance induced by the concerted migratory syn-insertion of coordinated cis-5-decene into the palladium alkylboron bond in the transition state. Similar observations were reported by James et al.26 in the carbomethoxypalladation reaction of trans- and cis-2-butene.
Conditions: 0.117 mmol (1.0 equiv.) of alkene, ICH2BF3K (1.2 equiv.), K2CO3 (5.0 equiv.),
4.4a (5 mol%), 1.1a (5 mol%), solvents: DMA:EG (16:1), 75°C, 24 h.
Scheme 4.3. Cyclopropanation of cis and trans-5-decene.
Methylenation reaction of a linear terminal alkene
The cyclopropanation reaction of 1-octene (4.1o) presented in Table 4.7 highlights the strong influence of the β-hydride elimination on the catalytic outcome as multiple consecutive methylene inserted products, both branched and linear, are observed alongside the corresponding cyclopropanes. Note that the homologated products come from further cyclopropanation of the olefins produced in situ by the undesired Heck/protodeboronation pathway. 98 | Chapter 4
Table 4.7. Cyclopropanation reaction of 1-octene.
No. 4.2oa 4.2pa 4.2qa 4.1oa 4.3oaa 4.3oba 4.1pa 4.3pa 4.1qa 4.1ra Totala
1 29 9 2 12 7 2 10 2 5 2 80
aYields in percentage were evaluated by GC–FID. 4.1o*: 0.117 mmol.
Limitation on yields
Control experiments were performed to ascertain the cause of lower cyclopropanation yield
for some of the substrates. The low yield obtained with α-pinene, cyclohexene and cis-5- decene, particularly, arises because the reaction is simply slow with these substrates. No deposition of palladium black was present after 22 h at 75 °C. With α-pinene, 1 additional
equiv. of ICH2BF3K added to the reaction after 18 h at 75 °C resulted in an increase of
cyclopropanation yield to 74% 24 h later (against 55% after 22 h at the same temperature),
indicating that the catalyst remained active. Secondly, a control reaction under otherwise
“standard conditions”, but with no olefinic substrate, gave no palladium black after 16 h at
75 °C. Subsequent addition of 1 equiv. of cyclooctene to that flask gave 53% yield of the
cyclopropane after 24 h (against 94% yield at the same temperature and time when
cyclooctene is added from the beginning). This experiment shows that (1) a dimeric reservoir
has to be cleaved by an olefin and only then can the catalyst decompose, and (2) the
methylenating agent ICH2BF3K slowly decomposes, or converts into a less reactive reagent,
under the reaction conditions when no olefin is available into which insertion can occur. This Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 99
should represent a limitation of the present reaction for less reactive olefins. Lastly, more
reactive olefins, for which the cleavage of the dimeric reservoir species is more efficient, e.g.
trans-5-decene, do show formation of palladium black, which signals that the reaction has ended with catalyst decomposition. For the unprotected allyl alcohols, an aldehydic oxidation
(side)-product was identified in the case of myrtenol (4.1f), although the extend of oxidation of the allylic alcohol to the corresponding aldehyde is surprisingly small.
4.5. Rationalization of the results and mechanistic proposal
While the NMR and ESI–MS investigations of the intermediates in the catalytic cycle support the proposed “diverted Heck” mechanism, the kinetics of cyclopropanation, as determined by the RPKA present a challenge to that hypothesis. In the most likely interpretation, the overall kinetics of the reaction are determined by the rate of transformation of a dinuclear Pd species bearing at least molecule of EG into a monomeric, active Pd complex, with release of one molecule of EG. This transformation would be unsurprisingly dependent on ligand and solvent, which offers an opportunity for the engineering of a catalytic reaction with broader substrate scope and preparatively useful yields. Targets for a mechanism-based reaction engineering were two-fold: suppression of the identified side reaction in which a terminal methylene group, rather than cyclopropanation, is formed, and increase in the rate of reaction so that it can handle substrates less reactive than norbornene.
The branching between the cyclopropane, the “diverted Heck” product, and the terminal methylene, the product of protodeboronation after a normal Heck reaction, would be determined by the relative rates of intramolecular transmetalation versus β-hydride elimination for the intermediate formed by migratory insertion of the olefinic substrate. In the original report, norbornene gave excellent yields of cyclopropanation already, but β- hydride elimination would have had to re-form the strained double bond, and can be expected to be disfavored. For other olefins, in our case, cyclooctene, or acyclic α-olefins, the β-hydride elimination is less disfavored, leading to significant formation of the terminal methylene product after protodeboronation. 100 | Chapter 4
Alternatively, the branching between intramolecular transmetalation and β-hydride elimination could be shifted by selectively accelerating the transmetalation. Transmetalation of the trifluoroborates has been reported to require prior hydrolysis or alcoholysis, and an acceleration by nucleophilic assistance is well-documented.27 The nucleophilic solvents, DMF
or DMA, the hydroxylic additives ranging from water to methanol to ethylene glycol, and
the base, either fluoride or carbonate, are all already components in the successful
cyclopropanation. A reported nucleophilicity order of –OH << MeO–< EtO– < n-PrO– < i-
PrO– in ROH–MeCN mixtures28 is consistent with our observation that alcohols, as an
additive, provide higher selectivity for cyclopropanation than does water. Moreover, EG
presumably affords a faster alcoholysis than a comparable monobasic alcohol with the same
nucleophilicity because of chelate effects. The latter effect is further consistent with the
decreased advantage offered by lower temperature in the DMA/EG solvent system, a
presumably chelate-promoted alcoholysis accelerating transmetalation sufficiently that it out-
competes β-hydride elimination even at higher temperatures.
Engineering a broader substrate scope for olefins less reactive than norbornene is made more difficult by the temperature reduction used to improve selectivity for cyclopropanation. The
kinetic studies, however, find that the overall rate appears to be controlled by the cleavage
of a presumed dinuclear Pd complex into an active monomeric species. An analogous
interpretation had been given for the observations by van Leeuwen, as well as Pfaltz and
Blackmond, of 0.5 kinetic order in Pd for Heck reactions.29 The zeroth order found for the
olefin, COE, and the methylene transfer agent, as well as the inverse half order in EG,
together with the intermediates observed in our investigations, can be rationalized by the
detailed proposed mechanism shown in Scheme 4.4, which we present as a mechanism
consistent with our experimental observations, but not necessarily exclusively. After the
oxidative addition of iodomethylboron species to the Pd(0) complex and substitution of the
halide to VI, the dinuclear structure VI would inhibit the occurrence of an undesired, and
catalytically unproductive, β-hydride elimination that one would ordinarily expect from a Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 101
Pd(II) complex with a primary alkoxide ligand under the reaction conditions.13 An increase
in the amount of EG in solution would decrease the concentration of the Pd-dimeric complexes
VI leading to less stable Pd-alkoxo monomers. An associative displacement of one of the two
oxygens of EG on VI by the olefin generates the postulated dinuclear Pd(II) resting state VII.
Electron-rich alkenes that are not sterically hindered like COE should bind favorably to
Pd(II) under the reaction conditions to open the alkoxo-bridged intermediate VI. Mechanistic
investigations on the opening of halo-bridged palladacycles by pyridine has been shown to
follow a fast and bimolecular associative pathway.30 The cleavage of the dinuclear Pd resting
state should operate through a reversible and concerted alkoxide-assisted deprotometalation31 mechanism on the ortho methyl C(sp3)–H bond of the ligand 1.1a, leading to the release of
the bridging alkoxide and formation of the palladacycle intermediate VIII. The release of one
molecule of EG would produce the –0.5 kinetic order in EG observed experimentally. A strong
base like t-BuONa had already been used to mediate the C(sp3)–H functionalization at a
benzylic sp3 position.32 Additionally, the close proximity between the Pd metal and the ortho
methyl C(sp3)–H bond of the ligand 1.1a (Tolman cone angle33 of 194°) supports the
occurrence of the concerted deprotometalation process. This could explain why catalysts able to form alkyl-phosphapalladacycles work so well in this reaction. A similar cyclometalation to a palladacycle is known from Pd(II) polymerization catalysts.34 The palladacycle
intermediate VIII formed after the deprotonation step is destabilized by the new C(sp3)–Pd bond trans to the alkylboron moiety (Scheme 4.5). Such a primary alkyl anion possesses a stronger trans influence compared to the phosphine in the palladacycle,35 which should accelerate the migratory insertion.36 102 | Chapter 4
the kinetics and the the ation of alkenes based on e Pd-catalyzed cyclopropan OH. 2 CH 2 .4. Proposed detailed mechanism for th Scheme 4 observed or isolated intermediates. R = CH Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 103
Based on the zero-order dependence observed for both COE and ICH2BF3K, this migratory
insertion must be the turnover-limiting step. Similar zero-order dependence on the olefin had
been reported by Brookhart for Pd(II)-catalyzed olefin polymerization, for which the resting
state had been identified to be the olefin π-complex, and the turnover-limiting step the
migratory insertion.34 The resulting palladacycle product IX could either undergo an
intramolecular transmetalation via the transition state TS[IX-X’] depicted in Scheme 4.4 to give the palladacyclobutane X’ or proceed with a β-hydride elimination to generate the intermediate X. Reductive elimination from these two intermediates will regenerate the Pd(0) complex V. The solvents utilized in this reaction are good coordinating nucleophiles and their coordination to the organometallic reagents helps stabilize the metal catalyst and thus extend its lifetime.
Scheme 4.5. Proposed concerted metalation-deprotonation mechanism and comparison of the π-complexes involved.
Another major role played by DMA or DMF is to ensure the solubility of the metal catalyst, the methylene transfer agent, as well as the inorganic base during the methylenation reaction.
The nucleophilicity is not the sole relevant performance metric for a given additive. For
example, although we observe a general trend in which the reaction is improved as the
conjugate base of the hydroxylic component (H2O, MeOH, other aliphatic alcohols) becomes
more nucleophilic in reference reactions,28 we observed only traces of products when EG was
replaced by pinacol, even in the presence of 2.0 equiv. of methanol (used to ensure the
reduction of Pd(II) to Pd(0)). We attribute this result to the steric hindrance of pinacol, 104 | Chapter 4
which makes the alcoholysis of the trifluoroborate extremely slow (Figure 4.15), counteracting the favorable effect of what would have been an otherwise more nucleophilic, chelating alkoxide. Similarly, while EG helps to improve the selectivity for transmetalation over β-
hydride elimination, the observed –0.5 kinetic order with respect to EG means that increasing
the EG concentration slows the overall turnover frequency. Accordingly, we find a non-
monotonic dependence of the cyclopropane yield on the EG content in the reaction mixture.
These examples serve to illustrate the complicated interplay of factors which make reaction
optimization less transparent than one would have wished.
19 Figure 4.15. F NMR spectra of the alcoholysis of ICH2BF3K in DMA, in the presence of pinacol in A) and EG in B).
Pd–Catalyzed Cyclopropanation of Electron–rich Alkenes and Allylic Alcohols | 105
4.6. Conclusions
Screening of the reaction conditions and components (co-solvent, ligands) coupled to the
spectroscopic observations and identifications of relevant intermediates, and the kinetic
studies on the cyclopropanation reaction of COE gave us an insight into the mechanism of
the catalytic cyclopropanation reaction. The reduction of the temperature as well as the use
of a bidentate primary diol, such as EG, as nucleophilic co-solvent, led to a better stabilization
of the Pd catalyst in solution and an improved conversion of COE into bicyclo[6.1.0]nonane.
The bridged, dimeric Pd reservoir formed during the catalysis prevents the occurrence of the
side β-hydride elimination process from the alkoxide. Moreover, using EG instead of water
reduces the rate of the undesired protodeboronation reaction. These investigations once again
supported the “diverted Heck” mechanism and permitted to broaden the substrate scope of the reaction to other di- and trisubstituted electron-rich olefins and allylic alcohols in
moderate to excellent yields. However, the cyclopropanation of sterically hindered and linear
olefins remains one of the biggest challenges of the method.
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Chapter 5
Conclusions and Outlook
Catalytic carbopalladation reactions of alkenes are widely employed strategies for the
preparation of drugs, fungicides, pesticides, dyes, functional polymers, and other chemicals.
The most renowned of these strategies, the Mizoroki-Heck reaction, owes its industrial
application to the rigor of the early research conducted in laboratories. The control reactions on the Mizoroki-Heck reaction pointed out the participation of palladium nanoparticles formed after the degradation of the well-defined Pd-catalyst in the observed catalysis. This allowed further investigations which led to the development of more robust palladacycle catalysts and highly active systems, such as the Herrman-Beller and the Bedford catalysts.
The carbopalladation of polar olefins to form functionalized polymeric materials using the
SHOP phosphine sulfonate (P∼O) ligand has shown a great potential in the incorporation of methyl acrylate into a polyethylene chain. However, the limited activity of the catalyst due to deactivation as well as the lack of critical interpretations of the (co)polymerization outcome and related control reactions do not promote the advancement of the (co)polymerization
process towards its industrial application. Nonetheless, the in situ formation of a catalytically
active Pd(0) intermediate en route to the pathway of irreversible catalyst deactivation, and the possibility to initiate its regeneration, thus improving the catalyst performance justified the study conducted in Chapter 2 of this thesis. The regeneration was shown to be possible in the presence of oxidative addition agents. However, the relentless occurrence of the β- 110 | Chapter 5
hydride elimination represented a challenge to the worthiness of the catalyst in situ
regeneration operation. This observation coupled to the possible Pd-induced radical nature
of the reported MA polymerizations forced us to end our efforts in developing strategies
towards a Pd-catalyzed living (co)polymerization of polar olefins. Further studies on the
strategies which will minimize the occurrence of the β-hydride elimination during the
(co)polymerization of polar olefins with the (P∼O)-based systems may be worth conducted,
as its may find an application in many other carbopalladation reactions. These strategies
could focus on the tuning of the electronic and steric properties of the phosphine sulfonate
ligands and/or the immobilization of the catalysts.
The studies carried out on the mechanism of the newly developed strategy for the cyclopropanation reaction of norbornene were the subject of the second carbopalladation reaction study presented in this thesis. Based on a mechanistic model named “diverted-Heck”, the coordination-insertion of norbornene (NBE) was followed by an intramolecular Suzuki- type transmetalation leading to the quantitative formation of tricyclo[3.2.1.02,4]octane. The
observation and isolation of the intermediates corresponding to the products of the oxidative
addition of the iodomethyl boron species used as methylenating reagent as well as the
formation of the cyclopropane product in the gas phase from a NBE-inserted Pd intermediate
represented the major results of our investigations. These results confirmed our initial
hypothesis on the mechanism represented by the mechanistic model. DFT calculations were
performed to support the experimental observations and showed the feasibility of the
transmetalation in the gas phase, without external assistance. However, the crucial role of
the external assistance in solution was highlighted in Chapter 4 when we expanded the
scope of the reaction to more challenging substrates. The replacement of methanol by ethylene
glycol as co-solvent, one among other optimizations, reduced the rate of the catalyst
deactivation and led to the conversion of cyclooctene into bicyclo[6.1.0]nonane via the
“diverted-Heck” in excellent yield and selectivity over the Heck product. Substituted alkenes,
such as α-pinene, an unusually challenging substrate for the well-established Simmons-Smith Conclusions and Outlook | 111
procedures, were cyclopropanated in satisfactory yields. Yet, some substrates remained a
challenge due to their steric crowding.
The work described in these last chapters has led to major understandings of the parameters governing the catalytic performance of this novel cyclopropanation reaction. They are solid bases for the development of a catalytic system of great industrial potential. The most important features of the catalytic system are represented in Figure 5.1.
electron-donor X increases the stability of the catalyst X X
o prone to deprotometalation to generate a strong -donor alkyl ligand, enhancing the P [B] migration ability of the alkyl group at the Pd trans position X O R1 o deactivation pathway via P-C reductive R2 elimination disfavored increases the electrophilicity of the metal center thus favoring the coordination of electron-rich olefins
Figure 5.1. Plausible features of the catalytic system for the cyclopropanation of electron- rich olefins.
The combination of the mechanistic investigations, the multiple control reactions, and the
outcome of the cyclopropanation of some electron-rich alkenes has left no room for doubt about the involvement of the phosphine ligand bound-Pd as catalyst, as well as the
carbopalladation-type nature of the catalysis. Nonetheless, some aspects of the reaction need
further dedication. The challenges we faced with some sterically hindered substrates might
be overcome by the design of a more robust ligand, preferably a monophosphine ligand, with
reduced steric hindrance like the o-tolyldibenzophosphole ligand 4.11 with adjusted electronic
and/or structural properties to prevent its dissociation by the olefin. Furthermore, a higher
TON (in the reasonable range of at least 103) should be sought. In comparison, the maximum
TON reached for the cyclopropanation of COE and presented in this work is only of ∼150. 112 | Chapter 5
An asymmetric version of the cyclopropanation reaction would favor the formation of a single
stereoisomer with excellent enantiomeric purity. The use of highly stereoselective catalysts
based on ligands bearing an o-tolyl or a tert-butyl group, such as the corresponding hemilabile
bis-phosphine mono-oxide ligands (Scheme 5.1), represents a convenient starting point for
these studies. The presence of the weakly binding phosphine-oxide is important as by ligand
rotation, it would still allow the concerted-metalation-deprotometalation step to take place.
Scheme 5.1. Potential ligands for the asymmetric cyclopropanation of electron-rich alkenes using iodomethylboron species.
Chapter 6
Experimental
6.1. General remarks
Unless otherwise stated, all reactions were carried out under an Argon or N2 atmosphere using
standard Schlenk or glovebox techniques with anhydrous solvents. Solvents and reagents were
acquired from Aldrich, Fluka, Acros Organics, ABCR Chemicals and TCI. Deuterated
solvents were obtained from Amar Chemicals. Extra molecular sieves were added to the
purchased solvents and the solvents stored in the glovebox. N,N-dimethylacetamide
(>= 99.5%, over molecular sieves [H2O <= 0.01%]) and ethylene glycol anhydrous (98.5%)
were acquired from Sigma-Aldrich and stored in the glovebox before use ICH2BF3K (> 98.0%)
was acquired from TCI and further purified by washing several times with Et2O and dried under high vacuum, then stored in the glovebox. Tri(o-tolyl)phosphine (1.2a, 97%),
dichlorobis(tri-o-tolylphosphine)palladium(II) (4.4a, 97%), t-BuXPhos Pd G3 (97%),
bis(dibenzylideneacetone)palladium (0), dichloro(1,5-cyclooctadiene)palladium(II)
([COD]PdCl2, 99%), and [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II)
(4.8b, 98%) were acquired from Sigma-Aldrich and used as received. Bicyclo[6.1.0]nonane
(4.2a), bicyclo[4.1.0]heptane (or norcarane, 4.2d) and n-hexylcyclopropane (4.2o) were
prepared according to a reported procedure.1 Methylenecyclooctane (4.3a) was prepared
according to a reported procedure.2 The obtained data are consistent with those reported in 114 | Chapter 6
the reference. 2,7,7-Trimethyltricyclo[4.1.1.02,4]octane (4.2e) was prepared following a
reported procedure.3 2-Methylenehexan-1-ol (4.3h) was prepared from n-hexanal according
to literature,4 and the obtained data matched those reported in that reference. 2-Methylpent-
2-en-1-ol (4.1g) was prepared from 2-methyl-2-pentenal according to a procedure reported in the literature.5 NMR data were recorded at 300, 400 or 600 MHz (Bruker AV300, AV400,
AV600 spectrometers) with CDCl3, CD3OD, THF-d8 or DMF-d7 as solvents. Chemical shifts
(δ) are reported in ppm with the residual solvent signal as internal standard (chloroform at
7.26 ppm and 77.00 ppm for 1H and 13C spectroscopy, respectively; methanol at δ 3.31 and
49.00 ppm for 1H and 13C spectroscopy, respectively; tetrahydrofuran at δ 3.58 and 67.57 ppm
for 1H and 13C spectroscopy, respectively; dimethylformamide at δ 2.75, 2.92, and 8.03 ppm
for 1H spectroscopy). 13C NMR spectra were recorded with complete 1H-decoupling. Service
measurements were performed by the NMR service team of the Laboratorium für Organische
Chemie, ETH Zürich. X-ray structural analysis was performed by the X-ray crystallography
group of the Laboratorium für Organische Chemie, ETH Zürich. High resolution mass spectra
were recorded from the mass spectrometry service of the ETH Zürich Laboratorium für
Organische Chemie with a Micromass (Waters) AutoSpec Ultima (EI) or a Bruker solariX
(MALDI-FTICR). GC-FID analysis was performed on a Finnigan Focus GC with a Zebron
ZB-5MS, 30 m x 0.25 mm column or a Restek Rtx-Wax, 30 m x 0.25 mm column using a
flame ionization detector. Qualitative gas phase studies were performed on a Thermo Finnigan
TSQ Quantum ESI–MS/MS instrument. Charged species were generated by electrospray
ionization (ESI) from diluted (∼10-5 mol L-1) solutions freshly prepared in the glovebox, taken
into a Hamilton gas-tight syringe and used immediately. All samples were electrosprayed with a flow rate of 5 mL/min.
6.2. Ligands synthesis
2-(bis(2-methoxyphenyl)phosphino)benzenesulfonic acid (1.4a). 1.4a was prepared from a known procedure.6
Experimental | 115
Sodium 2-(bis(2-methoxyphenyl)phosphino)benzenesulfonate (1.4aNa). Under
inert atmosphere, a 100 mL Schlenk flask was charged with the ligand 1.4a (634 mg, 1.58
mmol, 1.1 equiv.), NaH (34.4 mg, 1.43 mmol, 1.0 equiv.) and dichloromethane (20 mL). The
mixture was stirred overnight at ambient temperature. A white precipitate was present and
was filtered, washed with DCM (3 x 15 mL) and dried in vacuo to give the title product
1 quantitatively as a white solid. H NMR (300 MHz, DMSO-d6) δ 7.88 (ddt, J = 7.9, 4.1, 1.2
Hz, 1H), 7.33 – 7.21 (m, 3H), 7.13 (tt, J = 7.4, 1.4 Hz, 1H), 6.94 (dd, J = 8.3, 4.6 Hz, 2H),
6.77 (t, J = 7.4 Hz, 2H), 6.73 – 6.66 (m, 1H), 6.46 – 6.36 (m, 2H), 3.61 (s, 6H). 31P NMR
(121 MHz, DMSO-d6) δ -28.38.
2-(bis(2-methoxy-6-methylphenyl)phosphino)benzenesulfonic acid (1.4b).
Chlorobis(2-methoxy-6-methylphenyl)phosphine. To a solution of 2-bromo-1-methoxy-3- methylbenzene (1.74 g, 8.63 mmol, 1.0 equiv.) in dry pentane (20 mL) at 0 °C, n-BuLi ( 5.7
mL, 1.6 M in hexane, 9.06 mmol, 1.05 equiv.) was added dropwise over 5 min with observed
formation of a white precipitate. The slurry was stirred for 30 min at that temperature, then
5 min at room temperature. The resulting precipitate was separated and washed with pentane
to yield a white solid and the reaction vessel was cooled down to –78 °C. A cooled (–78 °C)
solution of Et2O (25 mL) was added. To the mixture under stirring was added dropwise a
cooled (–78 °C) solution of Cl2PNEt2 (572.2 μL, 3.93 mmol, 0.5 equiv.) in Et2O (10 mL).
After 30 min at –78 °C, the resulting mixture was warmed to room temperature and stirred
for 1.5 h. The white suspension was filtered off using cannula filtration and washed with 2 x
15 mL of Et2O. HCl gas was bubbled through over 30 min to give a white suspension.
Filtration and evaporation of the solvent under vacuum yielded 1.0 g (82%) of a yellowish
1 solid. The product was used without further purification. H NMR (300 MHz, DMSO-d6) δ
7.25 (m, 2H), 6.84 – 6.70 (m, 4H), 3.45 – 3.36 (m, 6H), 2.62 (s, 6H). 31P NMR (122 MHz,
DMSO-d6) δ 27.71.
2-(bis(2-methoxy-6-methylphenyl)phosphino)benzenesulfonic acid (1.4b). A procedure similar
to the procedure used to prepare the ligand 1.4a was followed. 880 mg (70%) of a white 116 | Chapter 6
1 crystals was obtained after recrystallization from dichloromethane/Et2O. H NMR (400 MHz,
CDCl3) δ 9.44 (d, J = 573.8 Hz, 1H), 8.35 (ddd, J = 7.8, 5.2, 1.3 Hz, 1H), 7.72 (tt, J = 7.6,
1.8 Hz, 1H), 7.57 – 7.34 (m, 4H), 6.93 (dd, J = 7.6, 4.9 Hz, 2H), 6.85 (dd, J = 8.4, 5.4 Hz,
13 2H), 3.58 (s, 6H), 2.28 (s, 6H). C NMR (101 MHz, CDCl3) δ 161.35 (s), 152.45 (d, J = 9.5
Hz), 144.52 (d, J = 6.2 Hz), 135.03 (s), 134.65 (d, J = 12.3 Hz), 134.55 – 134.48 (m), 129.84
(d, J = 13.3 Hz), 129.31 (d, J = 9.5 Hz), 125.10 (d, J = 11.2 Hz), 115.32 (d, J = 95.6 Hz),
110.16 (d, J = 5.4 Hz), 109.39 (d, J = 95.7 Hz), 56.47 (s), 21.44 (d, J = 8.9 Hz). 31P NMR
(162 MHz, CDCl3) δ -22.30. Elemental analysis: Anal. Calcd for C22H23O5PS: C, 61.39; H,
5.39. Found: C, 61.13; H, 5.25.
2-(bis(2-fluoro-6-methoxyphenyl)phosphino)benzenesulfonic acid (1.4c).
Chlorobis(2-fluoro-6-methoxyphenyl)phosphine. To a solution of 2-bromo-1-fluoro-3- methoxybenzene (2.5 g, 12.2 mmol, 1.0 equiv.) in dry THF (20 mL) at –78 °C, n-BuLi (7.62 mL, 1.6 M in hexane, 12.2 mmol, 1.0 equiv.) in dry THF (15 mL) was added dropwise. The colorless mixture was stirred for 1 h at that temperature. To the mixture was added dropwise a cooled (–78 °C) solution of Cl2PNEt2 (887 μL, 6.1 mmol, 0.5 equiv.) in THF (10 mL). After
30 min at –78 °C, the resulting mixture was warmed to room temperature and stirred for 1.5 h. The solvent was removed under vacuum and Et2O (20 mL) was added to dissolve the
product which was cannula-filtered to another Schlenk flask. The LiCl solid left was washed with an additional 2 x 15 mL of Et2O. A saturated solution of HCl in Et2O (2 N, 12.2 mL,
24.4 mmol, 2.0 equiv.) was added and the resulting slurry was stirred for 1 h. The precipitate
was cannula-filtered off and rinsed with Et2O (2 x 15 mL). The solvent was evaporated under
vacuum to yield 1.75 g (91%) of the product as a light orange solid. It was used without
1 further purification. H NMR (300 MHz, CD2Cl2) δ 7.46 – 7.25 (m, 2H), 6.71 (m, 4.0 Hz, 4H),
31 19 3.77 (s, 6H). P NMR (122 MHz, CD2Cl2) δ 47.65 (t, J = 18.0 Hz). F NMR (282 MHz,
CD2Cl2) δ -102.63 (dp, J = 18.0, 5.4 Hz).
2-(bis(2-fluoro-6-methoxyphenyl)phosphino)benzenesulfonic acid (1.4c). To a solution of dry benzenesulfonic acid (0.425 g, 2.68 mmol, 1.0 equiv.) in THF (10 mL) at 0 °C, n-BuLi (3.36 mL, 1.6 M in hexane, 5.36 mmol, 2.0 equiv.) was added dropwise over 5 min, and the mixture Experimental | 117
was stirred for 15 min at this temperature. The reaction mixture was warmed to room
temperature for 5 min, then 50 °C for 15 min and cooled down to –78 °C before the addition
dropwise of a cooled (–78 °C) THF (10 mL) solution of chlorobis(2-fluoro-6-
methoxyphenyl)phosphine (0.85 g, 2.68 mmol, 1.0 equiv.). The reaction mixture was stirred
at that temperature for 1 h, then warmed to ambient temperature and stirred for additional
4 h. The volatiles were removed in vacuo leaving an orange solid which was dissolved in dichloromethane (20 mL) and deionized water (20 mL) added. The mixture was acidified under stirring with concentrated HCl (4 mL, 37% in water). After extraction with dichloromethane (2 × 15 mL), the crude product was dried over MgSO4, and the solvent was
removed in vacuo. The desired product was recrystallised from dichloromethane/hexane to
1 afford 812 mg (69 %) of a white solid. H NMR (400 MHz, CD2Cl2) δ 8.21 – 8.14 (m, 1H),
7.83 – 7.74 (m, 1H), 7.72 – 7.63 (m, 2H), 7.52 – 7.42 (m, 2H), 7.00 – 6.49 (m, 5H), 3.81 (s,
13 6H). C NMR (101 MHz, CD2Cl2) δ 166.52 (s), 163.99 (s), 162.60 – 162.17 (m), 152.97 (d, J
= 10.7 Hz), 137.88 (d, J = 11.7 Hz), 135.40 (s), 134.63 (d, J = 13.1 Hz), 130.18 (d, J = 14.2
Hz), 129.10 (d, J = 10.3 Hz), 109.75 (d, J = 5.6 Hz), 109.53 (d, J = 5.7 Hz), 108.36 (d, J =
31 19 5.5 Hz), 57.60 (s). P NMR (162 MHz, CD2Cl2) δ -32.36 (brs). F NMR (377 MHz, CD2Cl2)
δ -102.29 and -102.32 (two singlets or one doublet?). HRMS (ESI–QTOF) calcd for
+ + C20H18F2O5PS [M+H ] 439.0575, found 439.0575.
2-(bis(2,6-dimethoxyphenyl)phosphino)benzenesulfonic acid (1.4d). Chlorobis(2,6-
dimethoxyphenyl)phosphine. To a solution of dimethylresorcinol (1.5 g, 10.9 mmol, 1.0 equiv.)
in dry THF (10 mL) at –5 °C, n-BuLi (6.8 mL, 1.6 M in hexane, 10.9 mmol, 1.0 equiv.) in
dry THF (10 mL) was added dropwise over 30 min and the resulting mixture was stirred for
1 h at that temperature. To the mixture was added dropwise a cooled (0 °C) solution of
Cl2PNEt2 (790 μL, 5.4 mmol, 0.5 equiv.) in THF (10 mL). After 30 min at 0 °C, the resulting
mixture was warmed to room temperature and stirred for 1.5 h. an orange solution was
present. A saturated solution of HCl in Et2O (2 N, 8.1 mL, 16.3 mmol, 1.5 equiv.) was added
and the resulting slurry was stirred for 1 h. The volatiles were removed in vacuo and toluene
(20 mL) was added. The solution was filtered off through cannula to a Schlenk flask. 2 x 10 118 | Chapter 6
mL of toluene were used to rinse the remaining white precipitate. The solvent was evaporated
under vacuum to yield 1.5 g of the crude product (purity according to 31P NMR = about
70%) as a light yellow solid which was used without further purification. 31P NMR (122 MHz,
CD2Cl2) δ 60.62.
2-(bis(2,6-dimethoxyphenyl)phosphino)benzenesulfonic acid (1.4d). A procedure similar to
the procedure used to prepare the ligand 1.4a was followed. 1.1 g (49%) of white crystals was
1 obtained after recrystallization from dichloromethane/Et2O. H NMR (400 MHz, CD2Cl2) δ
9.33 (d, J = 601.0 Hz, 1H), 8.17 – 8.10 (m, 1H), 7.70 – 7.64 (m, 1H), 7.57 (t, J = 8.5 Hz, 2H),
7.49 – 7.37 (m, 2H), 6.64 (dd, J = 8.4, 5.2 Hz, 4H), 3.64 (s, 12H). 13C NMR (101 MHz,
CD2Cl2) δ 163.15 (s), 152.36 (d, J = 10.1 Hz), 136.69 (s), 134.63 (d, J = 12.2 Hz), 133.78 (d,
J = 3.2 Hz), 129.36 (d, J = 13.6 Hz), 128.83 (d, J = 9.9 Hz), 116.20 (d, J = 103.1 Hz), 105.14
31 (d, J = 6.3 Hz), 98.27 (d, J = 102.0 Hz), 56.87 (s). P NMR (162 MHz, CD2Cl2) δ -28.52.
+ + HRMS (ESI-QTOF) calcd for C22H24O7PS [M+H ] 463.0975, found 463.0971.
2-(bis(2,6-diethoxyphenyl)phosphino)benzenesulfonic acid (1.4e). Chlorobis(2,6-
diethoxyphenyl)phosphine. The title compound was prepared in 0.85 g in a crude form (purity
according to 31P NMR = about 70%) from 1,3-diethoxybenzene following a procedure analogous to the one used for 1.4d and used without further purification. 31P NMR (122
MHz, CD2Cl2) δ 63.96.
2-(bis(2,6-diethoxyphenyl)phosphino)benzenesulfonic acid (1.4e). A procedure similar to the procedure used to prepare the ligand 1.4a was followed. 0.9 g (46%) of white crystals was
1 obtained after recrystallization from dichloromethane/Et2O. H NMR (400 MHz, CD2Cl2) δ
9.35 (d, J = 600.0 Hz, 1H), 8.14 (ddd, J = 8.0, 5.4, 1.2 Hz, 1H), 7.66 (tdd, J = 7.6, 2.2, 1.3
Hz, 1H), 7.59 – 7.48 (m, 3H), 7.38 (tdd, J = 7.6, 2.6, 1.3 Hz, 1H), 6.58 (dd, J = 8.5, 5.4 Hz,
13 4H), 3.93 (q, J = 7.0 Hz, 8H), 0.99 (t, J = 7.0 Hz, 12H). C NMR (101 MHz, CD2Cl2) δ
162.48 (s), 152.69 (d, J = 10.0 Hz), 136.39 (s), 135.09 (d, J = 11.9 Hz), 133.69 (d, J = 3.3
Hz), 129.44 (d, J = 13.4 Hz), 128.73 (d, J = 9.9 Hz), 117.05 (d, J = 102.0 Hz), 105.15 (d, J
31 = 6.5 Hz), 97.91 (d, J = 102.3 Hz), 65.37 (s), 14.19 (s). P NMR (162 MHz, CD2Cl2) δ -
+ + 30.01. HRMS (ESI–QTOF) calcd for C26H32O7PS [M+H ] 519.1601, found 519.1598. Experimental | 119
(2,3,5,6,8,9,11,12-octahydrobenzo[b][1,4,7,10,13]pentaoxacyclopentadecin-15-yl)-
diphenylphosphine (crown-ether ligand). The title ligand was prepared analogously to
a reported procedure.7 The product was obtained in 67% yield as a white crystalline solid. 1H
NMR (400 MHz, CDCl3) δ 7.35 – 7.25 (m, 10H), 6.89 – 6.79 (m, 3H), 4.15 – 4.11 (m, 2H),
4.02 – 3.97 (m, 2H), 3.93 – 3.89 (m, 2H), 3.86 – 3.82 (m, 2H), 3.75 (d, J = 5.9 Hz, 8H). 13C
NMR (101 MHz, CDCl3) δ 150.09 (s), 149.17 (d, J = 9.2 Hz), 137.85 (d, J = 10.7 Hz), 133.60
(d, J = 19.1 Hz), 128.69 (s), 128.57 (d, J = 6.7 Hz), 127.75 (d, J = 20.5 Hz), 119.32 (d, J =
22.6 Hz), 113.76 (d, J = 8.7 Hz), 71.30 (s), 70.64 (d, J = 3.6 Hz), 69.67 (d, J = 2.8 Hz), 68.96
31 (d, J = 8.3 Hz). P NMR (162 MHz, CDCl3) δ -5.38.
Tris(2-methyl-4-fluorophenyl)phosphine (1.1b). The title compound was prepared
8 1 quantitatively according to a reported procedure. H NMR (400 MHz, CDCl3) δ 7.02 – 6.92
3 4 13 (m, 3H), 6.80 (td, JHH = 8.5 Hz and JHH = 2.7 Hz, 3H), 6.69-6.60 (m, 3H), 2.37 (s, 9H). C
1 1 4 NMR (101 MHz, CDCl3) δ 163.42 (d, JCF = 248.5 Hz), 145.19 (dd, JCP = 28.5 Hz, JCF =
2 2 3 7.8 Hz), 134.67 (d, JCP = 8.1 Hz), 129.50 (dd, JCP = 10.6 Hz, JCF = 3.3 Hz), 117.29 (dd,
2 3 2 3 3 JCF = 20.7 Hz, JCP = 5.1 Hz), 113.29 (dd, JCF = 20.3 Hz, JCP = 1.1 Hz), 21.15 (dd, JCP
4 31 5 19 = 21.9 Hz, JCF = 1.7 Hz). P NMR (162 MHz, CDCl3) δ -33.64 (q, JPF = 3.0 Hz). F NMR
5 (376 MHz, CDCl3) δ -113.42 (d, JFP = 4.3 Hz).
Tris(2-methyl-4-(trifluoromethyl)phenyl)phosphine (1.1d). The title compound was
prepared as an orange solid in 97% analogously to a reported procedure9 using 1-bromo-2-
1 methyl-4-(trifluoromethyl)benzene. H NMR (400 MHz, CDCl3) δ 7.57 – 7.47 (m, 1H), 7.36
(m, J = 8.2, 1.8 Hz, 1H), 6.78 (dd, J = 8.0, 3.8 Hz, 1H), 2.44 (s, 3H). 31P NMR (162 MHz,
19 13 CDCl3) δ -29.11. F NMR (376 MHz, CDCl3) δ -62.91. C NMR (101 MHz, CDCl3) δ 143.81
1 2 2 (d, JCP = 27.3 Hz), 137.83 (d, JCP = 13.2 Hz), 133.39 (s), 131.65 (q, JCF = 32.3 Hz), 127.12
3 1 3 3 (p, JCF = 3.7 Hz), 124.12 (d, JCF = 272.4 Hz), 123.30 (q, JCF = 3.7 Hz), 21.39 (d, JCP =
21.5 Hz).
3-(2-(di-o-tolylphosphino)phenyl)-1-phenylprop-2-en-1-one (4.6). The title ligand
was prepared analogously to a reported procedure10 using chlorodi-o-tolylphosphine. 0.64 g
1 (64%) of product was obtained as a white crystal. Rf (Hexane/EtOAc (95/5)) = 0.17. H 120 | Chapter 6
NMR (400 MHz, CDCl3) δ 8.33 (dd, J = 15.9, 4.9 Hz, 1H), 7.82 – 7.74 (m, 1H), 7.68 – 7.60
(m, 2H), 7.58 – 7.47 (m, 1H), 7.49 – 7.38 (m, 1H), 7.37 (m, 2H), 7.32 – 7.23 (m, 6H), 7.15
(dd, J = 15.9, 1.2 Hz, 1H), 7.15 – 7.04 (m, 2H), 6.89 (ddd, J = 7.7, 4.0, 1.2 Hz, 1H), 6.74
13 (ddd, J = 7.7, 4.5, 1.2 Hz, 2H), 2.38 (d, J = 1.4 Hz, 6H). C NMR (101 MHz, CDCl3) δ
192.55 (s), 143.73 (d, J = 25.1 Hz), 142.91 (d, J = 26.7 Hz), 140.18 (d, J = 22.5 Hz), 138.16
(s), 137.22 (d, J = 15.2 Hz), 134.11 (d, J = 10.1 Hz), 134.10 (s), 133.55 (s), 132.46 (s), 130.37
(d, J = 5.0 Hz), 130.24 (s), 129.27 (s), 129.16 (s), 128.82 (s), 128.57 (s), 127.17 (d, J = 4.1
Hz), 126.41 (d, J = 1.0 Hz), 125.83 (d, J = 3.4 Hz), 21.41 (d, J = 21.7 Hz).31P NMR (162
MHz, CDCl3) δ -29.47. Elemental analysis: Anal. Calcd for C29H25OP: C, 82.84; H, 5.99.
Found: C, 85.79; H, 5.96.
1,2-Bis(di-o-tolylphosphino)ethane. The title compound was prepared as described
11 1 3 earlier and obtained in 76% as white crystals. H NMR (400 MHz, CDCl3) δ 7.21 (td, JHH
4 3 4 = 7.3 Hz and JHH = 1.5 Hz, 4H), 7.18 – 7.12 (m, 4H), 7.09 (td, JHH = 7.3 Hz and JHH =
3 31 1.5 Hz, 4H), 7.06 – 7.00 (m, 4H), 2.40 (s, 12H), 2.06 (t, JHH = 4.3 Hz, 4H). P NMR (162
13 MHz, CDCl3) δ -33.64. C NMR (101 MHz, CDCl3) δ 142.84 – 142.23 (m), 136.36 (t, J = 6.9
Hz), 131.08, 130.06 (t, J = 2.5 Hz), 128.46, 126.03, 22.69 (d, J = 3.7 Hz), 21.42 – 21.05 (m).
1,1’-Bis(di-o-tolylphosphino)ferrocene. The title compound was prepared by a procedure
analogous to the one used for the synthesis of 1,2-bis(di-o-tolylphosphino)ethane and was
1 obtained in 64% (white solid). H NMR (400 MHz, CDCl3) δ 7.23 – 7.08 (m, 2H), 7.23 – 7.08
3 3 (m, 2H), 6.99 – 6.93 (m, 1H), 4.25 (t, JHH = 1.8 Hz, 1H), 4.07 (q, JHH = 1.8 Hz, 1H), 2.47
31 13 (s, 3H). P NMR (162 MHz, CDCl3) δ -37.32. C NMR (101 MHz, CDCl3) δ 141.67 (d, J =
26.7 Hz), 137.55 (d, J = 11.0 Hz), 133.32 (s), 129.82 (d, J = 5.0 Hz), 128.42 (s), 125.53 (d, J
= 1.2 Hz), 76.62 (s, probably a doublet with second peak collapsing with the solvent peaks),
74.18 (d, J = 15.3 Hz), 72.17 (dd, J = 3.9, 1.2 Hz), 21.32 (d, J = 22.0 Hz).
n-Butyldi-o-tolylphosphine (4.10). To a solution of chlorodi-o-tolylphosphine (1.0 g, 4.0
mmol) in Et2O (10 mL) at –78 °C was added under stirring a cooled (–78 °C) solution of n-
BuLi (2.5 mL, 1.6 M in hexanes, 4.0 mmol). The temperature of the reaction mixture was
raised gradually to 0 °C (ca. 3 h), then to room temperature and the reaction was stirred for Experimental | 121
another 2 h. Cannula-filtration of the yellow solution to a round bottom flask followed with
washing with additional Et2O (2 x 5 mL). The volatiles were removed in vacuo yielding 0.89
1 g (81%) of the product as a white solid. H NMR (400 MHz, CDCl3) δ 7.31 – 7.05 (m, 8H),
2.42 (s, 6H), 2.04 – 1.89 (m, 2H), 1.45 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 142.49 (d, J = 24.9 Hz), 137.42 (d, J = 13.5 Hz), 131.21 (s), 130.09 (d, J = 4.7 Hz),
128.40 (s), 126.10 (s), 28.31 (d, J = 16.5 Hz), 26.97 (d, J = 11.0 Hz), 24.60 (d, J = 13.2 Hz),
31 21.40 (d, J = 21.3 Hz), 13.97 (s). P NMR (162 MHz, CDCl3) δ -38.01. Elemental analysis:
Anal. Calcd for C18H23P: C, 79.97; H, 8.57. Found: C, 79.76; H, 8.70.
5-(o-tolyl)-5H-benzo[b]phosphindole (o-tolyldibenzophosphole, 4.11). To a cooled
(0 °C) solution of 2,2’-dibromobiphenyl (2.0 g, 6.4 mmol) in Et2O (40 mL), n-BuLi (8.0 mL,
1.6 M in hexanes, 12.8 mmol) was added dropwise over 15 min under stirring. The reaction
vessel was brought to ambient temperature and the yellowish solution was stirred for 1 h. At
the end of this time, the solution was cooled down to –78 °C before the addition dropwise of
a solution of Cl2PNEt2 (933 µL, 6.4 mmol) in Et2O (5 mL). The resulting mixture was allowed to warm to room temperature and was stirred overnight. HCl in Et2O (4.8 mL, 2 N, 9.6
mmol) was added at to the reaction mixture cooled to 0 °C and the resulting slurry was
stirred for 30 min, followed by filtration through cannula to another Schlenk flask and
evaporation of the volatiles to give a yellowish solid. Et2O (25 mL) was added to dissolve the
solid and the yellow solution was cooled down to 0 °C. A freshly prepared solution of o-
tolyllithium (from 2-bromoanisole (1.1 mL, 9.6 mmol) and n-BuLi (5.2 mL, 8.3 mmol at 0
°C)) at 0 °C was added dropwise to the mixture under stirring. A dark brown mixture was
formed and was stirred for 2 h. Degassed H2O (25 mL) was added and the product extracted with Et2O (2 x 25 mL), dried over MgSO4 and concentrated to give an oil which crystallized
on standing at 0 °C. Recrystallization from ethanol and drying in vacuo yielded 1.2 g (67 %)
1 of the product as colorless crystals. H NMR (400 MHz, CDCl3) δ 8.03 (m, 2H), 7.79 – 7.69
(m, 2H), 7.52 (td, J = 7.5, 1.2 Hz, 2H), 7.37 (tdd, J = 7.5, 2.9, 1.2 Hz, 2H), 7.31 – 7.25 (m,
1H), 7.25 – 7.20 (m, 1H), 6.98 – 6.92 (m, 1H), 6.74 (m, 1H), 2.85 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 143.74 (d, J = 3.7 Hz), 143.48 (d, J = 25.8 Hz), 143.17 (d, J = 3.1 Hz), 134.52 (d, 122 | Chapter 6
J = 19.4 Hz), 132.29 (d, J = 4.0 Hz), 130.53 (d, J = 5.2 Hz), 130.48 (d, J = 21.5 Hz), 129.65
(d, J = 1.2 Hz), 128.54, 127.59 (d, J = 7.4 Hz), 126.29 (d, J = 3.1 Hz), 121.60, 22.15 (d, J =
31 21.5 Hz). P NMR (162 MHz, CDCl3) δ -18.62. Elemental analysis: Anal. Calcd for C19H15P:
C, 83.20; H, 5.51. Found: C, 82.96; H, 5.52.
8-(4-methoxy-2-methylphenyl)-1,3,5,7-tetramethyl-2,4,6-trioxa-8-phosphaada- mantane (4.12). The title ligand was prepared analogously to a reported procedure12 using
1-bromo-4-methoxy-2-methylbenzene as substrate. 0.85 g (80%) of product was obtained as
1 a white crystal. Rf (Hexane/Et2O (5/1)) = 0.42. H NMR (400 MHz, CDCl3) δ 8.12 – 8.05
(m, 1H), 6.84 – 6.69 (m, 2H), 3.80 (s, 3H), 2.58 (s, 3H), 2.10 (m, 1H), 1.94 (m, 2H), 1.49 –
13 1.41 (m, 10H), 1.25 (d, J = 12.3 Hz, 3H). C NMR (101 MHz, CDCl3) δ 160.50 (s), 147.44
(d, J = 29.7 Hz), 134.98 (d, J = 3.1 Hz), 123.17 (d, J = 25.5 Hz), 116.22 (d, J = 5.9 Hz),
111.76 (s), 97.00 (s), 96.19 (s), 74.20 (d, J = 8.1 Hz), 73.61 (d, J = 22.4 Hz), 55.19 (s), 46.34
(d, J = 19.0 Hz), 36.15 (d, J = 2.0 Hz), 28.13 (d, J = 27.7 Hz), 27.96 (d, J = 20.3 Hz), 26.79
31 (d, J = 11.2 Hz), 22.46 (d, J = 25.5 Hz). P NMR (162 MHz, CDCl3) δ -40.27. Elemental
analysis: Anal. Calcd for C18H25O4P: C, 64.27; H, 7.49. Found: C, 64.03; H, 7.50.
6.3. Complexes synthesis
Bis{N,N’-{(κ2-P,O)-2-[di(2-methoxyphenyl)phosphino]benzenesulphonato}
palladium(II)-methyl}-N,N,N’,N’-tetramethylethylenediamine (2.16a). The titled
complex was synthesized in 97% (280 mg) yield as a white solid according to a reported procedure.13 THF was used as solvent instead of dioxane. The obtained data are consistent
with those reported in the reference.
{(κ2-P,O)-2-[di(2-methoxyphenyl)phosphino]benzenesulphonato} (dimethyl
sulfoxide) palladium(II)-methyl (1.5a). The title compound was prepared in 68% (148
13 1 mg) from 2.16a according to a reported procedure. H NMR (400 MHz, CDCl3) δ 8.18 (ddd,
J = 7.9, 4.8, 1.4 Hz, 1H), 7.56 – 7.34 (m, 5H), 7.31 – 7.26 (m, 1H), 7.20 (ddd, J = 11.4, 7.9,
1.4 Hz, 1H), 7.01 (tt, J = 7.4, 1.4 Hz, 2H), 6.92 (dd, J = 8.1, 5.0 Hz, 3H), 3.65 (s, 6H), 3.03
13 (s, 6H), 0.44 (d, J = 2.2 Hz, 3H). C NMR (101 MHz, CDCl3) δ 160.53 (d, J = 3.2 Hz), Experimental | 123
148.13 (d, J = 14.5 Hz), 137.17, 134.46, 133.61, 130.63, 129.01 (d, J = 7.2 Hz), 128.35 (d, J
= 8.3 Hz), 127.24 (d, J = 50.4 Hz), 121.00 (d, J = 11.4 Hz), 115.60 (d, J = 57.4 Hz), 111.41
31 (d, J = 4.8 Hz), 55.47, 41.66, 3.30. P NMR (162 MHz, CDCl3) δ 16.90 (brs).
Bis{N,N’-{(κ2-P,O)-2-[di(2-methoxy-6-methylphenyl)phosphino]benzenesulpho-
nato}palladium(II)-methyl}-N,N,N’,N’-tetramethylethylenediamine (2.16b). 58.7 mg (0.23 mmol) of (TMEDA)PdMe2 and 100 mg (0.23 mmol) of 1.4b were dissolved in 10
mL of dry THF under inert atmosphere and stirred for 1 h. Gas evolution was spontaneous.
Then, 20 mL of anhydrous Et2O were added and the mixture stirred for 2 h. The resulting
light yellow precipitate was collected, washed with Et2O then pentane, and dried in vacuo
overnight. The yield was 112 mg (80%). Recrystallization was done in
1 dichloromethane/pentane. H NMR (400 MHz, CD2Cl2) δ 7.99 (m, 2H), 7.51 (m, 2H), 7.39
(tq, J = 7.5, 1.6 Hz, 2H), 7.34 – 7.21 (m, 6H), 6.87 (tt, J = 8.4, 3.3 Hz, 4H), 6.66 (m, 4H),
3.41 (d, J = 1.6 Hz, 6H), 3.40 – 3.29 (m, 4H), 3.27 (d, J = 2.9 Hz, 6H), 3.12 (s, 3H), 3.07 (s,
3H), 2.71 (d, J = 3.5 Hz, 6H), 2.63 – 2.49 (m, 12H), 0.10 – 0.07 (m, 6H). 13C NMR (101 MHz,
CD2Cl2) δ 162.21 (d, J = 1.1 Hz), 161.27 (d, J = 4.7 Hz), 148.04 (d, J = 15.0 Hz), 144.52 (d,
J = 4.4 Hz), 144.39 (d, J = 3.9 Hz), 143.38 (d, J = 9.5 Hz), 143.27 (d, J = 9.5 Hz), 136.34
(d, J = 6.3 Hz), 131.60 (s), 131.50 (d, J = 5.7 Hz), 130.37 (d, J = 5.7 Hz), 130.29 (t, J = 2.4
Hz), 129.87 (d, J = 5.6 Hz), 128.17 (d, J = 6.9 Hz), 127.93 (d, J = 8.3 Hz), 125.25 (t, J =
9.0 Hz), 119.48 (d, J = 9.0 Hz), 118.96 (d, J = 10.2 Hz), 118.46 (d, J = 4.2 Hz), 108.66 (d, J
= 2.8 Hz), 108.34 (d, J = 4.2 Hz), 108.27 (d, J = 4.2 Hz), 59.74, 55.29 (d, J = 3.2 Hz), 54.88
(d, J = 3.7 Hz), 50.73 (d, J = 38.5 Hz), 50.35 (d, J = 33.3 Hz), 25.96 (d, J = 11.7 Hz), 25.75
(d, J = 11.7 Hz), 25.36 (d, J = 7.4 Hz), 25.24 (d, J = 7.4 Hz), 2.02 (t, J = 4.0 Hz). 31P NMR
(162 MHz, CD2Cl2) δ -2.60 (s) and -2.78 (s). HRMS (ESI–QTOF) calcd for
+ + C52H67N2O10P2Pd2S2 [M+H ] 1219.1800, found 1219.1787.
Bis{N,N’-{(κ2-P,O)-2-[di(2-fluoro-6-methoxyphenyl)phosphino]benzenesulpho-
nato}palladium(II)-methyl}-N,N,N’,N’-tetramethylethylenediamine (2.16c). The
titled complex was prepared analogously to 2.14a. 130 mg (94%) of white solid was obtained.
31 The product was poorly soluble even in DMSO. P NMR (121 MHz, DMSO-d6) δ -14.15 124 | Chapter 6
19 (brs). F NMR (282 MHz, DMSO-d6) δ -95.70 (brs), -100.28 (s). HRMS (ESI–QTOF) calcd
+ + for C48H55F4O10P2Pd2S2 [M+H ] 1233.0776, found 1233.0804.
{(κ2-P,O)-2-[bis(2-fluoro-6-methoxyphenyl)phosphino]benzenesulphonato}
pyridine palladium(II)-methyl (2.16c-pyr). 29 mg (0.115 mmol) of (TMEDA)PdMe2 and 50 mg (0.115 mmol) of 1.4c were dissolved in 10 mL of dry THF under inert atmosphere and stirred for 1 h. After addition of pyridine (46 µL, 0.575 mmol), a clear solution formed immediately. Stirring was continued for 30 min, the volatiles were removed under reduced pressure and the yellow solid was washed several times with Et2O and pentane to yield 52
1 mg (71%). Recrystallization was done in dichloromethane/Et2O. H NMR (300 MHz, CD2Cl2)
δ 8.78 – 8.68 (m, 2H), 8.03 (ddd, J = 7.8, 5.2, 1.4 Hz, 1H), 7.88 (tt, J = 7.8, 1.7 Hz, 1H), 7.55
– 7.40 (m, 6H), 7.30 (tt, J = 7.6, 1.4 Hz, 1H), 6.79 (s, 2H), 6.69 (s, 2H), 3.71 (s, 3H), 3.56 (s,
31 3H), 0.30 (dt, J = 3.5, 1.2 Hz, 3H). P NMR (122 MHz, CD2Cl2) δ -12.38 (d, J = 32.2 Hz).
19 F NMR (282 MHz, CD2Cl2) δ -96.65 (d, J = 32.2 Hz), -100.57.
Bis{N,N’-{(κ2-P,O)-2-[di(2,6-dimethoxyphenyl)phosphino]benzenesulphonato}
palladium(II)-methyl}-N,N,N’,N’-tetramethylethylenediamine (2.16d). The titled
complex was prepared analogously to 2.16a. 102 mg (74%) of light yellow solid was obtained.
1 The product was poorly soluble in dichloromethane. H NMR (300 MHz, CD2Cl2) δ 8.03 –
7.88 (m, 2H), 7.35 (m, 8H), 7.18 (t, J = 7.5 Hz, 2H), 6.53 (dd, J = 8.4, 4.1 Hz, 8H), 3.78 –
31 3.23 (m, 28H), 2.50 (s, 12H), 0.18 – -0.08 (m, 6H). P NMR (122 MHz, CD2Cl2) δ -6.92.
Bis{N,N’-{(κ2-P,O)-2-[di(2,6-diethoxyphenyl)phosphino]benzenesulphonato}
palladium(II)-methyl}-N,N,N’,N’-tetramethylethylenediamine (2.16e). 49 mg
(0.19 mmol) of (TMEDA)PdMe2 and 100 mg (0.19 mmol) of 2-(bis(2,6-
diethoxyphenyl)phosphino)benzenesulfonic acid (1.4e) were dissolved in 10 mL of dry THF
under inert atmosphere and stirred for 2 h. Gas evolution was spontaneous. The resulting
orange solution was evaporated and the residue washed with Et2O then pentane, and dried
in vacuo overnight to give the product quantitatively as a yellow solid. Recrystallization was
1 done in dichloromethane/Et2O. H NMR (400 MHz, CD2Cl2) δ 7.93 (ddd, J = 7.9, 4.8, 1.4 Hz, Experimental | 125
2H), 7.47 (ddd, J = 11.3, 7.9, 1.4 Hz, 2H), 7.32 (m, 6H), 7.16 – 7.08 (m, 2H), 6.46 (dd, J =
8.4, 4.0 Hz, 8H), 3.93 – 3.71 (m, 16H), 3.07 (t, J = 1.9 Hz, 3H), 2.62 (s, 1H), 2.51 (s, 1H),
2.41 (d, J = 1.9 Hz, 9H), 2.32 (s, 2H), 0.91 (q, J = 7.0 Hz, 24H), 0.15 (d, J = 1.9 Hz, 6H).
13 C NMR (101 MHz, CD2Cl2) δ 161.51 (d, J = 1.5 Hz), 148.87 (d, J = 16.0 Hz), 134.67,
132.23, 131.58 (d, J = 53.0 Hz), 129.37, 128.13 (d, J = 3.7 Hz), 128.06 (d, J = 5.2 Hz), 107.55
(d, J = 53.9 Hz), 104.57 (d, J = 4.7 Hz), 64.30, 59.98, 50.27 (d, J = 2.1 Hz), 14.41, 2.10 (d,
31 J = 2.2 Hz). P NMR (162 MHz, CD2Cl2) δ -6.34. HRMS (ESI–QTOF) calcd for
+ + C60H83N2O14P2Pd2S2 [M+H ] 1395.2852, found 1395.2863.
{(κ2-P,O)-2-[Di(2-methoxyphenyl)phosphino]benzenesulphonato} pyridine
palladium(II)-(1-methoxy-1-oxopropan-2-yl) (2.8b). 750 mg (1.30 mmol, 1.05 equiv.)
of Pd(dba)2 and 0.5 g (1.24 mmol) of the ligand 1.4a were dissolved in anhydrous DMA (10
mL) under inert atmosphere and stirred for 30 min in the dark at room temperature. Methyl
acrylate (335 μl, 3.72 mmol, 3.0 equiv.) and pyridine (200 μl, 2.48 mmol, 2.0 equiv.) were
added successively by syringe and the reaction mixture was stirred for another 20 min. The
solvent was removed under reduced pressure. The residue was washed with Et2O (2 x 10 mL) and pentane (2 x 10 mL) under inert atmosphere before the addition of a solution of DCM
(10 mL), and filtrated. The flask and the filter were rinsed with DCM (2 x 5 mL). A solution of Et2O (10 mL) was added to this solution and the solvents removed under rotary evaporator
in the absence of a heating bath. Yellow microcrystals, suitable for X-ray appeared in the
flask and were collected by filtration. The same operation is repeated two more times on the
resulting solution. The product is washed with pentane and dried overnight in vacuo. 425 mg
1 (51%) of the complex was obtained as a pale yellow solid. H NMR (400 MHz, CD2Cl2) δ 8.86
– 8.73 (m, 3H), 7.95 (ddd, J = 7.7, 4.9, 1.4 Hz, 1H), 7.89 (tt, J = 7.7, 1.7 Hz, 1H), 7.64 – 7.55
(m, 2H), 7.52 – 7.36 (m, 5H), 7.31 (tt, J = 7.7, 1.4 Hz, 1H), 7.21 (tdd, J = 7.5, 2.0, 1.0 Hz,
1H), 7.07 – 7.01 (m, 2H), 6.92 (ddd, J = 8.3, 4.1, 1.0 Hz, 1H), 3.72 (s, 3H), 3.59 (s, 3H), 3.31
(s, 3H), 2.16 (dq, J = 10.4, 7.0 Hz, 1H), 0.33 (dd, J = 7.0, 4.6 Hz, 3H). 13C NMR (101 MHz,
CD2Cl2) δ 179.67 (s), 161.51 (s), 161.03 (d, J = 3.7 Hz), 151.33 – 150.90 (m), 148.42 (d, J =
14.9 Hz), 142.85 (d, J = 20.4 Hz), 138.94 (s), 136.14 (d, J = 8.1 Hz), 135.42 (s), 134.72 (s), 126 | Chapter 6
133.82 (s), 130.71 (s), 128.66 (d, J = 7.6 Hz), 127.64 (d, J = 8.4 Hz), 127.30 (d, J = 52.2 Hz),
125.63 (s), 121.19 (d, J = 10.4 Hz), 120.99 (d, J = 14.9 Hz), 115.81 – 113.96 (m), 111.74 (dd,
J = 46.0, 4.4 Hz), 56.02 (s), 55.29 (s), 51.00 (s), 20.69 (s), 14.95 (s). 31P NMR (162 MHz,
CD2Cl2) δ 19.63. Elemental analysis: Anal. Calcd for C29H30NO7PSPd: C, 51.68; H, 4.49; N,
2.08. Found: C, 51.42; H, 4.43; N, 2.04.
{(κ2-P,O)-2-[Di(2-methoxyphenyl)phosphino]benzenesulphonato} acetonitrile
palladium(II)-phenyl (2.14). In the glovebox, a 50 mL Schlenk flask was charged with
1.4aNa (100 mg, 0.236 mmol, 1.0 equiv.), Pd(dba)2 (162.6 mg, 0.283 mmol, 1.2 equiv.) and
THF (8 mL). The mixture was stirred at room temperature for 30 min. To the resulting dark
red mixture was added PhI (78.1 μl, 0.708 mmol, 3.0 equiv.). The color of the reaction then
turned from dark red to green in 10 min. After 15 min, the solvent was removed in vacuo.
AgOTf (91.0 mg, 0.354 mmol, 1.5 equiv.) in MeCN/DCM (1 mL/5 mL) was added in the
dark. A precipitate appeared and the mixture was stirred for another 15 min. The yellow
solution was cannula-filtered over Celite, washed with DCM (2 x 4 mL) and the solvents
evaporated. The resulting solid was washed several times with pentane and dried under
reduced pressure to give 133 mg (90%) of the product as a pale yellow solid. Crystals were
obtained from a solution of the solid in a small volume of MeCN cooled to -20 °C. 1H NMR
(400 MHz, CD2Cl2) δ 8.06 (ddd, J = 7.9, 4.9, 1.3 Hz, 1H), 8.03 – 7.91 (m, 2H), 7.64 – 7.58
(m, 2H), 7.54 (tt, J = 7.6, 1.6 Hz, 1H), 7.47 – 7.29 (m, 3H), 7.11 (tt, J = 6.9, 2.0 Hz, 4H),
6.89 (ddd, J = 8.5, 4.9, 1.0 Hz, 2H), 6.84 – 6.73 (m, 3H), 3.59 (s, 6H), 2.14 (s, 3H). 31P NMR
(162 MHz, CD2Cl2) δ 19.04.Elemental analysis: Anal. Calcd for C28H26NO5PSPd: C, 53.73;
H, 4.19; N, 2.24. Found: C, 53.55; H, 4.15; N, 2.40.
Chloro(1,5-cyclooctadiene)methylpalladium(II). The title complex was prepared in
86% yield (1.2 g) according to a reported procedure14 and recrystallized from
1 chloroform/diethyl ether. H NMR (400 MHz, CDCl3) δ 5.93 (ddt, J = 5.6, 3.5, 1.2 Hz, 2H),
5.24 – 5.11 (m, 2H), 2.74 – 2.53 (m, 4H), 2.53 – 2.41 (m, 4H), 1.19 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 123.99, 100.99, 31.18, 27.79, 12.51.
Experimental | 127
Dichlorobis((tri-2-methyl-4-fluorophenyl)phosphine)palladium(II) (4.4b). The title
31 catalyst was prepared in 71% yield (165 mg) as a yellow solid. P NMR (122 MHz, CDCl3)
δ 19.68 (brs). Elemental analysis: Anal. Calcd for C42H36F6P2Cl2Pd: C, 56.43; H, 4.06; F,
12.75; P, 6.93; Cl, 7.93. Found: C, 56.52; H, 3.94; F, 12.58; P, 6.72; Cl, 7.83.
Dichlorobis(tri-2,4-dimethylphenyl)phosphine)palladium(II) (4.4c). 31P NMR (162
MHz, CDCl3) δ 20.42 (brs). Elemental analysis: Anal. Calcd for C48H54P2Cl2Pd: C, 66.25; H,
6.25; P, 7.12; Cl, 8.15. Found: C, 65.92; H, 6.26; P, 6.93; Cl, 8.29.
Dichlorobis(tri-2-methyl-4-(trifluoromethyl)phenyl)phosphine)palladium(II)
(4.4d). The title catalyst was prepared in 91% yield (281 mg) as a yellow solid. 31P NMR
19 (162 MHz, CD2Cl2) δ 22.23 (brs). F NMR (377 MHz CD2Cl2) δ -63.55 (s).
[1,2-Bis(di-o-tolylphosphino)ethane]dichloropalladium(II) (4.7). 4.7 is poorly soluble
in non-coordinating solvents. HRMS (MALDI-FTICR/DCTB, ([M-Cl]+)): m/z calcd for
C30H32P2ClPd 595.0705; Found: 595.0685.
[1,1′-Bis(di-o-tolylphosphino)ferrocene]dichloropalladium(II) (4.8a). The product
31 was obtained as a brick red solid in 53% (110 mg) yield. P NMR (162 MHz, CDCl3) δ 40.34
(brs). Elemental analysis: Anal. Calcd for C83H80P4Cl4Fe2Pd2 (C38H36P2Cl2FePd + 0.5 toluene): C, 59.77; H, 4.83; P, 7.43; Cl, 8.50. Found: C, 59.53; H, 4.78; P, 7.53; Cl, 8.53.
(2-Di-tert-butylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)palladium(II)-
(trifluoro-λ4-boranyl)methyl (3.12). A 25 mL oven-dried round bottom flask was brought
into a N2-filled glovebox and charged with K2CO3 (136 mg, 4.0 equiv.), ICH2BF3K (183.4 mg,
3.0 equiv.), and DMF (1 mL). The Buchwald palladium precatalyst t-BuXPhos Pd G3 (196
mg, 0.246 mmol, 1.0 equiv.) in DMF (1 mL) was added into this mixture under stirring at
ambient temperature and the vial containing the precatalyst was rinsed with another 1 mL
DMF and transferred to the reaction mixture. Stirring was continued for 10 min before the
removal of the solvent by rotary evaporation. A mixture of DCM/pentane (5 mL/10 mL) was added to the resulting residue and filtered over Celite. The Celite filter cake was washed with
pentane (5 mL). The solvents were slowly evaporated on a rotary evaporator under moderate 128 | Chapter 6
vacuum (no water bath) until lots of clear green micro crystals appeared in the flask.
Evaporation was stopped and the crystals were isolated by filtration, washed with a small
volume of cold pentane, and dried under high vacuum. These crystals were suitable for X-ray
analysis. 126 mg of product are obtained (NMR reveals the presence of 9H-carbazole). 1H
3 4 NMR (400 MHz, CH2Cl2-d2) δ 7.99 (tq, JHH = 6.5 Hz and JHP = 2.2 Hz, 1H, aryl CH),
7.57-7.51 (m, 2H, aryl CH), 7.28 – 7.27 (m, 2H, aryl CH), 7.19 – 7.11 (m, 1H, aryl CH), 3.02
3 3 3 (hept, JHH = 6.9 Hz, 1H, i-Pr CH), 2.45 (hept, JHH = 6.7 Hz, 2H, i-Pr CH), 1.56 (d, JHH
3 3 = 6.8 Hz, 6H, i-Pr CH3), 1.48 (d, JHP = 15.1 Hz, 18H, t-Bu), 1.36 (d, JHH = 6.9 Hz, 6H, i-
3 3 – 3 Pr CH3), 1.19 (qd, JHF = 8.0 Hz and JHP = 1.6 Hz, 2H, PdCH2BF3 ), 0.95 (d, JHH = 6.6
31 4 19 Hz, 6H, i-Pr CH3). P NMR (162 MHz, CH2Cl2-d2) δ 75.42 (q, JPF = 32.6 Hz). F NMR
– 11 (376 MHz, CH2Cl2-d2) δ -140.53 (s, PdCH2BF3 ). B NMR (160 MHz, CH2Cl2-d2) δ 5.38 (s,
– + PdCH2BF3 ). HRMS (MALDI-FTICR/DCTB, ([M-BF3] )): m/z calcd for C30H47PPd
544.2456; Found: 544.2456.
6.4. Synthesis of other substrates
Benzene diazonium tosylate. The title compound was prepared analogously to a reported
15 1 procedure and kept at –36 °C. H NMR (300 MHz, DMSO-d6) δ 8.78 – 8.56 (m, 2H), 8.25
(t, J = 7.1 Hz, 1H), 7.97 (t, J = 7.7 Hz, 2H), 7.47 (d, J = 7.5 Hz, 2H), 7.10 (d, J = 7.6 Hz,
2H), 2.28 (s, 3H).
Benzene diazonium chloride. The title compound was prepared analogously to a reported
16 1 procedure , recrystallized at –20 °C from EtOH/Et2O and kept at –36 °C. H NMR (300
MHz, DMSO-d6) δ 8.87 – 8.71 (m, 1H), 8.33 – 8.17 (m, 1H), 8.08 – 7.89 (m, 1H).
4-Benzenediazoniumsulfonate. The title compound was prepared by diazotization of 4-
aminobenzenesulfonic acid17 and kept at –36 °C. It has a low solubility in DMSO. 1H NMR
(300 MHz, DMSO-d6) δ 8.64 (d, J = 8.8 Hz, 2H), 8.09 (d, J = 8.8 Hz, 2H).
4-Nitrobenzyl 4-nitrobenzenesulfonate. The title compound was prepared analogously
18 1 to a reported procedure and kept at –36 °C. H NMR (300 MHz, CDCl3) δ 8.45 – 8.38 (m,
1H), 8.27 – 8.20 (m, 1H), 8.19 – 8.08 (m, 1H), 7.58 – 7.43 (m, 1H), 5.26 (s, 1H). Experimental | 129
Bicyclo[6.1.0]nonane (4.2a). The title compound was prepared according to the following
representative procedure for the scale-up of the methylenation reaction of olefins to mmol
(gram) amounts:
Representative procedure for the scale-up of the methylenation reaction of olefins
to mmol (gram) amounts. A 250 mL oven-dried round-bottom flask equipped with an
oven-dried magnetic stir bar was charged in a N2-filled glovebox with powdered K2CO3 (4.04
g, 5.0 equiv.), anhydrous EG (5 mL), and anhydrous DMA (20 mL). The resulting mixture
was stirred vigorously. [(o-tolyl)3P]2PdCl2 (230 mg, 5 mol%), (o-tolyl)3P (89 mg, 5 mol%),
ICH2BF3K (2.18 g, 1.5 equiv.), and the olefin (5.85 mmol) were added to the mixture under
stirring. 60 mL of DMA were used to rinse the vials utilized to weigh all the reagents and
were subsequently added to the reaction mixture. The round bottom flask was then closed, removed from the glovebox, and stirred at 75 °C for the indicated time. At the end of the reaction, which was monitored by GC–MS, the flask was cooled to 0 °C and its contents were poured over Celite. The filter cake was washed with Et2O (3 x 50 mL). The filtrate was
transferred to a separatory funnel and H2O (200 mL) was added. The organic layer was separated and the aqueous layer was extracted with Et2O (2 x 100 mL). The fractions were
combined, dried over Na2SO4 or MgSO4, filtered, and the ether solution removed by a rotary
evaporator. The resulting oil residue was purified by flash column chromatography over silica
gel.
Flash chromatography using pentane as eluent and slow evaporation of the solvent yielded
654 mg (90%) of a mixture of bicyclo[6.1.0]nonane (4.2a) and methylenecyclooctane (4.3a)
(50:1 ratio of products in favor of the cyclopropane) as a colorless oil. MS (EI): 124 (32, [M]+),
+ 96 (94), 81 (77), 67 (100), 54 (73), 41 (27). HRMS (EI, ([M] )): m/z calcd for C9H16 124.1247;
Found 124.1247.
1-Methylbicyclo[3.1.0]hexane (4.2b). The procedure is analogous to the one reported in
the literature19 for the cyclopropanation of cyclopentene. A mixture of 27.5 g (0.213 mol, 2.5
eq.) of Zn/Cu couple and a crystal of iodine was stirred under 50 mL of dry ether under argon 130 | Chapter 6
until the brown color disappeared. A mixture of 7 g (0.085 mol) of 1-methylcyclopentene, and
17.2 mL (0.213 mol, 2.5 eq.) of methylene iodide was added in portion. The mixture was then
refluxed for 15 h. The mixture was filtered through Celite and poured into 40 mL of a cooled
saturated NH4Cl solution. The organic layer was separated and washed with 3 x 40 mL
NH4Cl, 3 x 40 mL NaHCO3 and 1 x 40 mL H2O. After drying over MgSO4, the solvent was
completely removed by distillation to yield 4.9 g (60%) of 1-methylbicyclo[3.1.0]hexane. 1H
NMR (400 MHz, CDCl3) δ 1.78 – 1.59 (m, 3H), 1.59 – 1.45 (m, 2H), 1.25 – 1.07 (m, 4H), 0.89
3 3 3 2 (dt, JHH = 8.0 Hz and JHH = 4.0 Hz, 1H), 0.30 (dd, JHH = 4.0 Hz, JHH = 4.6 Hz, 1H), 0.16
3 2 13 (dd, JHH = 8.0 Hz and JHH = 4.6 Hz, 1H). C NMR (101 MHz, CDCl3) δ 33.78, 27.93,
24.13, 23.93, 21.68, 21.54, 12.92. 13C NMR values are in accordance with the literature data.20
MS (EI): 96 (32, [M]+), 81 (100), 68 (30), 55 (28), 41 (8). HRMS (EI, ([M]+)): m/z calcd for
+ C7H12 96.0934; Found 96.0931. HRMS (EI, ([M-CH3] )): m/z calcd for C7H12 81.0699; Found
81.0699.
Bicyclo[5.1.0]octane (4.2c). The title compound was prepared by a similar procedure used
for the synthesis of 1-methylbicyclo[3.1.0]hexane. 4.5 g (79%) of 2c were obtained as a
1 colourless oil. H NMR (400 MHz, CDCl3) δ 2.22-2.05 (m, 2H), 1.89-1.77 (m, 1H), 1.76-1.64
(m, 2H), 1.42-1.28 (m, 2H), 1.27 – 1.05 (m, 1H), 1.00 – 0.73 (m, 4H), 0.68 (m, 1H), 0.07 (m,
13 + 1H). C NMR (101 MHz, CDCl3) δ 32.69, 31.07, 29.83, 16.43, 14.84. MS (EI): 110 (8, [M] ),
+ 95 (14), 81(25), 67 (35), 54 (18), 41 (15). HRMS EI, ([M] )): m/z calcd for C8H14 110.1090;
Found 110.1092.
2,7,7-Trimethyltricyclo[4.1.1.02,4]octane (4.2e). The title compound was prepared in 70
1 3 % as a colourless oil. H NMR (400 MHz, CDCl3) δ 2.13 – 2.01 (m, 2H), 1.89 (dd, JHH = 6.3
3 Hz and JHH = 5.1 Hz, 1H), 1.76 – 1.61 (m, 2H), 1.29 (s, 3H), 1.12 (s, 3H), 1.08 (s, 3H), 0.98
2 13 (d, JHH = 10.6 Hz, 1H), 0.82 – 0.71 (m, 2H), 0.31 – 0.20 (m, 1H). C NMR (101 MHz,
CDCl3) δ 45.38, 41.50, 40.93, 27.34, 26.99, 26.89, 26.83, 25.42, 21.00, 20.26, 18.90, 15.87. MS
+ (EI): 150 (3), 135 (32, [M-CH3] ), 109 (74), 94 (100), 82 (56), 69 (47), 55 (17), 41 (25). HRMS
+ (EI, ([M-CH3] )): m/z calcd for C10H15 135.1169; Found 135.1167.
Experimental | 131
(7,7-Dimethyltricyclo[4.1.1.02,4]octan-2-yl)methanol (4.2f). The title compound was prepared from a modified reported procedure.21 To a solution of (-)-myrtenol (2.5 g, 1.0 eq.) and diiodomethane (3.0 eq.) in dry toluene (20 mL), was added drop wise a 1 M solution of diethyl zinc (49.25 mL, 3.0 eq.) at –30 °C. Full conversion was observed within 2 h stirring at ambient temperature. The reaction was quenched at 0 °C by the addition of an aqueous
HCl solution (1 M) and extracted with diethyl ether. The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. The resulting oil was purified using a quick filtration over silica gel by eluting with a pentane/Et2O mixture (5/1). Concentration of the eluent under reduced pressure resulted in the compound as an orange oil (Rf (pentane/
1 2 Et2O (5/1)) = 0.17, 92% yield). H NMR (400 MHz, CDCl3) δ 3.89 (dd, JHH = 11.0 Hz and
3 2 3 3 JHH = 1.4 Hz, 1H), 3.02 (d, JHH = 11.0 Hz, 1H), 2.23 (dd, JHH = 6.4 Hz and JHH = 5.2
3 Hz, 1H), 2.15-2.07 (m, 1H), 2.07-1.98 (m, 1H), 1.75 – 1.64 (m, 2H), 1.36 (t, JHH = 5.2 Hz,
2 1H), 1.27 (s, 3H), 0.98 (s, 3H), 0.95 (d, JHH = 10.7 Hz, 1H), 0.93 – 0.83 (m, 2H), 0.45 (m,
13 1H). C NMR (101 MHz, CDCl3) δ 70.16, 41.49, 40.90, 40.67, 27.77, 26.91, 26.64, 26.38,
20.82, 15.89, 13.36. MS (EI): 166(1, [M]+), 148(12), 135 (27), 123 (17), 110 (76), 93 (43), 82
+ (100), 67 (71), 55 (31), 41 (44). HRMS (EI, ([M] )): m/z calcd for C11H18O 166.1353; Found
+ 166.1358. HRMS (EI, ([M-CH3O] )): m/z calcd for C10H15 135.1169; Found 135.1169.
The title compound was isolated in 86% following the representative procedure for the scale- up of the methylenation reaction of olefins to mmol (gram) amounts. Spectroscopic data
(NMR and MS) are the same as the one reported for 4.2f prepared above. HRMS (EI, ([M]+)): m/z calcd for C11H18O, 166.1353; Found 166.1353. ∼5.4% of the corresponding aldehyde (3f)
13 was isolated alongside the cyclopropane. C NMR (101 MHz, CDCl3) δ 202.72, 40.85, 40.54,
38.49, 37.34, 26.51, 26.17, 25.66, 20.84, 20.34, 17.23.
(2-Ethyl-1-methylcyclopropyl)methanol (4.2g). The title compound was prepared analogously to a reported procedure22 using 2-methylpent-2-en-1-ol as substrate. 2.1 g (31%)
1 of a colourless oil were obtained, Rf (Hexane/AcOEt(10/1)) = 0.25. H NMR (400 MHz,
3 CDCl3) δ 3.36 – 3.27 (m, 2H), 1.43 – 1.37 (m, 1H), 1.33 (p, JHH = 7.3 Hz, 2H), 1.13 (s, 3H),
3 3 3 3 0.96 (t, JHH = 7.3 Hz, 3H), 0.57 (dtd, JHH = 8.8 Hz, JHH = 6.9 Hz and JHH = 5.2 Hz, 1H), 132 | Chapter 6
3 2 13 0.50 (dd, JHH = 8.8 Hz and JHH = 4.2 Hz, 1H), -0.02 – -0.06 (m, 1H). C NMR (101 MHz,
+ CDCl3) δ 72.64, 23.77, 22.33, 22.31, 16.53, 15.11, 14.41. HRMS (EI, ([M-C2H5] )): m/z calcd
+ for C5H9O 85.0648; Found 85.0650. HRMS (EI, ([M-CH3O] )): m/z calcd for C6H11 83.0856;
Found 83.0857.
Trans-2-propylcyclopropylmethanol (4.2h). The title compound was prepared analogously to a reported procedure22 using (E)-hex-2-en-1-ol as substrate. Colourless oil,
1 20%, Rf (Hexane/AcOEt (4/1)) = 0.22. H NMR (400 MHz, CDCl3) δ 3.50 – 3.22 (m, 2H),
3 1.57 (s, 1H), 1.44 – 1.32 (m, 2H), 1.26 – 1.16 (m, 2H), 0.90 (t, JHH = 7.3 Hz, 3H), 0.86 – 0.76
2 3 2 (m, 1H), 0.63 – 0.53 (m, 1H), 0.35 (dt, JHH = 8.5 Hz and JHH =4.7 Hz, 1H), 0.29 (dt, JHH
3 13 = 8.5 Hz and JHH = 4.7 Hz, 1H). C NMR (101 MHz, CDCl3) δ 67.31, 35.85, 22.81, 21.25,
+ 17.05, 14.03, 9.99. MS (EI): 96(11, [M-H2O] ), 81 (39), 73 (65), 67 (22), 55 (100), 41 (56), 29
+ (12). HRMS (EI, ([M-H2O] )): m/z calcd for C7H12 96.0934; Found 96.0931.
Cis-2-propylcyclopropylmethanol (4.2i). The title compound was prepared analogously
22 to a reported procedure using (Z)-hex-2-en-1-ol as substrate. Colourless oil, 64%, Rf
1 (Hexane/AcOEt (4/1)) = 0.3. H NMR (400 MHz, CDCl3) δ 3.67 – 3.52 (m, 2H), 1.59 – 1.51
(m, 1H), 1.49 – 1.33 (m, 3H), 1.27 – 1.14 (m, 1H), 1.13 – 1.01 (m, 1H), 0.97 – 0.79 (m, 4H),
13 0.73 – 0.63 (m, 1H), -0.02 – -0.08 (m, 1H). C NMR (101 MHz, CDCl3) δ 62.98, 30.66, 23.17,
+ 17.90, 15.81, 13.94, 9.42. MS (EI): 96(10, [M-H2O] ), 81 (35), 73 (80), 67 (22), 55 (100), 41
+ (61), 29 (13). HRMS (EI, ([M-H2O] )): m/z calcd for C7H12 96.0934; Found 96.0929.
4,12,12-Trimethyl-9-methylenetricyclo[8.2.0.04,6]dodecane (4.2j). The title
compound was prepared according to the representative procedure for the scale-up of the
methylenation reaction of olefins to mmol (gram) amounts, and obtained as a colorless oil,
68%, Rf (Hexane) = 0.78. Analytical data (NMR) are consistent with the ones described in
12 + + the literature. MS (EI): 218 (6, [M] ), 203 (47, [M-CH3] ), 175 (55), 161 (44), 147 (44), 133
(60), 119 (34), 107 (85), 93 (100), 81 (58), 69 (90), 55 (27), 41 (18). HRMS (EI, ([M]+)): m/z
+ calcd for C16H26 218.2029; Found 218.2026. HRMS (EI, ([M-CH3] )): m/z calcd for C15H23
203.1795; Found 203.1799. Elemental analysis: Anal. Calcd for C16H26: C, 88.00; H, 12.00.
Found: C, 87.86.51; H, 12.25. Experimental | 133
Bicyclo[10.1.0]tridecane (4.2k). The title compound was prepared as a colorless oil, bp.
110 °C/13 mbar from cyclododecene (96% purity, contains some cyclododecane) by a similar
procedure used for the synthesis of 1-methylbicyclo[3.1.0]hexane. Analytical data (NMR, MS)
are consistent with the ones described in the literature.23
Tricyclo[4.2.0.02,4]octan-7-one (4.2m). The title compound was prepared from (+/-)-cis-
Bicyclo[3.2.0]hept-2-en-6-one in 77% as a light orange oil. Rf (Hexane/EtOAc (10/1)) = 0.33 according to the representative procedure for the scale-up of the methylenation reaction of
1 olefins to mmol (gram) amounts. Major isomer: H NMR (400 MHz, CDCl3) δ 3.38-3.24 (m,
3 1H), 3.16 – 3.01 (m, 1H), 2.89 – 2.77 (m, 2H), 2.30 – 2.17 (m, 1H), 1.93 (dd, JHH = 13.7 Hz
3 and JHH = 10.3 Hz, 1H), 1.54 – 1.47 (m, 1H), 1.47 – 1.41 (m, 1H), 0.75 – 0.66 (m, 1H), -0.07
13 – -0.13 (m, 1H). C NMR (101 MHz, CDCl3) δ 211.44, 63.92, 50.79, 34.72, 31.82, 25.42, 20.13,
13 13.16. Minor isomer: C NMR (101 MHz, CDCl3) δ 215.25, 67.89, 48.50, 31.84, 30.24, 25.22,
23.40, 8.79. MS (EI): 122 (2, [M]+), 80 (100), 68 (10), 55 (10). HRMS (EI, ([M]+)): HRMS
+ (EI, ([M] )): m/z calcd for C8H10O 122.0727; Found 122.0730.
Exo-Cyclopropanated Oxabenzonorbornadiene (4.2n). The title compound was
prepared according to the representative procedure for the scale-up of the methylenation
reaction of olefins to mmol (gram) amounts. An additional washing of the organic layers with
10% NaOH was included in the work-up. The product was obtained by column
chromatography in 26% yield as a colorless oil. Rf (Hexane/EtOAc (20/1)) = 0.36. Analytical
data (NMR) are consistent with the ones described in the literature.24 MS (EI): 158 (31,
+ + [M] ), 129 (100), 115 (13). HRMS (EI, ([M] )): m/z calcd for C11H10O, 158.0727; Found
158.0725. Elemental analysis: Anal. Calcd for C11H10O: C, 83.52; H, 6.37. Found: C, 83.51;
H, 6.43.
N-heptylcyclopropane (4.2p). The title compound was prepared by a similar procedure
used for the synthesis of 1-methylbicyclo[3.1.0]hexane in 78% as a colorless oil, bp. 57–59
1 °C/13 mbar. H NMR (400 MHz, CDCl3) δ 1.44 – 1.33 (m, 2H), 1.33 – 1.22 (m, 8H), 1.18 (q,
3 JHH = 7.0 Hz, 2H), 0.93 – 0.85 (m, 3H), 0.71 – 0.58 (m, 1H), 0.42 – 0.35 (m, 2H), 0.02 – - 134 | Chapter 6
13 0.04 (m, 2H). C NMR (101 MHz, CDCl3) δ 34.97, 32.10, 29.84, 29.70, 29.57, 22.87, 14.28,
11.08, 4.51. MS (EI): 140 (7), 112 (20), 97 (28), 83 (47), 70 (100), 56 (91), 43 (38).
N-octylcyclopropane (4.2q). The title compound was prepared by a similar procedure
used for the synthesis of 1-methylbicyclo[3.1.0]hexane in 66% as a colorless oil, bp. 72–75
1 °C/13 mbar. H NMR (400 MHz, CDCl3) δ 1.42 – 1.34 (m, 2H), 1.34 – 1.24 (m, 10H), 1.18
3 (q, JHH = 7.0 Hz, 2H), 0.92 – 0.85 (m, 3H), 0.71 – 0.59 (m, 1H), 0.42 – 0.35 (m, 2H), 0.02 –
13 -0.04 (m, 2H). C NMR (101 MHz, CDCl3) δ 34.98, 32.12, 29.88, 29.85, 29.76, 29.70, 29.55,
22.88, 14.28, 11.09, 4.52. MS (EI): 154 (5, [M]+), 126 (14), 111 (14), 97 (51), 83 (70), 70 (93),
+ 56 (100), 43 (68). HRMS (EI, ([M] )): m/z calcd for C11H22 154.1716; Found 154.1716.
Trans-1,2-dibutylcyclopropane (4.2s). The title compound was prepared by a similar
procedure used for the synthesis of 1-methylbicyclo[3.1.0]hexane in 72% as a colorless oil, bp.
1 3 63–64 °C/17 mbar. H NMR (400 MHz, CDCl3) δ 1.41 – 1.08 (m, 12H), 0.89 (t, JHH = 7.2
3 3 3 Hz, 6H), 0.36 (ddd, JHH = 7.2 Hz, JHH = 5.8 Hz, JHH = 4.2 Hz, 2H), 0.18 – 0.08 (m, 2H).
13C NMR (101 MHz, CDCl3) δ 34.23, 32.09, 22.74, 18.92, 14.31, 14.27, 11.92. MS (EI): 154
(37, [M]+), 111 (8), 97 (16), 83 (32), 69 (93), 55 (100), 43 (33). HRMS (EI, ([M]+)): m/z calcd for C11H22 154.1716; Found 154.1718.
Cis-1,2-dibutylcyclopropane (4.2t). The title compound was prepared by a similar
procedure used for the synthesis of 1-methylbicyclo[3.1.0]hexane. 4.2s was prepared in 72%
1 as a colorless oil, bp. 68 °C/17 mbar. H NMR (400 MHz, CDCl3) δ 1.45 – 1.27 (m, 10H),
1.21 – 1.10 (m, 2H), 0.96 – 0.85 (m, 6H), 0.70 – 0.61 (m, 2H), 0.60 – 0.52 (m, 1H), -0.33 (td,
3 2 13 JHH = 5.5 Hz and JHH = 4.0 Hz, 1H). C NMR (101 MHz, CDCl3) δ 32.63, 28.56, 22.86,
15.90, 14.33, 11.06. MS (EI): 154 (29, [M]+), 111 (11), 97 (28), 83 (27), 69 (81), 55 (100), 43
+ (34). HRMS (EI, ([M] )): m/z calcd for C11H22 154.1716; Found 154.1716.
Methylenecyclododecane (4.3k). The title compound was prepared from cyclododecanone
according to a modified procedure.25 At –78 °C under argon, a solution of
((trimethylsilyl)methyl)lithium 1 M in pentane (18 mL, 18 mmol) is added dropwise to a solution of cyclododecanone (3.28 g, 18 mmol) in THF (25 mL). The reaction mixture is stirred for 2 h at that temperature, after which time the reaction vessel was warmed to Experimental | 135
ambient temperature and stirred for another 15 min before the addition of 2% aqueous HCl
(200 mL) solution and followed by extraction with Et2O (3 x 100 mL). The organic layers are
dried (MgSO4) and the solvent evaporated to give a colorless oil that was stirred in a two- phase mixture composed of 60 mL of pentane and 60 mL of 50% aqueous acetic acid for ca.
18 h. The layers were separated and the organic phase was washed with water, dried
(Na2SO4), and concentrated under reduced pressure. Short column chromatography of the
residue with pentane yielded 1.07 g (33%) of 4.3k as a colorless oil, whose analytical data
(NMR) are consistent with the ones described in the literature.26 MS (EI): 180 (57, [M]+),
123 (17), 109 (40), 96 (100), 82 (98), 68 (62), 56 (80), 41 (18). HRMS (EI, ([M]+)): m/z calcd for C11H10O, 180.1873; Found 180.1876.
2-Methyloct-1-ene (4.3oa). The title compound was prepared according to the following procedure: a 2 M solution of n-pentylMgCl in THF (11 mL, 22 mmol) is added dropwise to a stirred solution of 3-bromo-2-methylprop-1-ene (2 mL, 20 mmol) in THF (160 mL) at 0 °C
under argon atmosphere. The resulting mixture was allowed to warm to room temperature
and was stirred overnight. The excess of Grignard reagent is quenched with diluted aqueous
HCl. Following an extraction with pentane (3 x 150 mL), washing the extract with H2O (2 x
200 mL), drying with Na2SO4, filtration, evaporation of the solvent, and distillation yielded
1.95 g (77%, traces of decane are present) of the title compound as a colorless oil. Analytical
data (NMR) are consistent with the ones described in the literature.27 MS (EI): 126 (23,
+ + [M] ), 98 (4), 69 (23), 56 (92), 43 (33), 18 (100). HRMS (EI, ([M] )): m/z calcd for C9H18
126.1403; Found 126.1400.
5-Methylenedecane (4.3s). The title compound was prepared analogously to a reported procedure.28 In brief, the preparation was carried out in a 250 mL flask previously dried and
filled with Argon. A solution of n-BuMgCl 2 M in Et2O (11 mL, 22 mmol) is added at ambient
temperature to a stirred solution of 2,3-dibromopropene (4g, 20 mmol) in THF (160mL).
After 18 h, (dppp)NiCl2 (345 mg, 0.64 mmol) is added to the mixture, then a solution of n-
BuMgCl 2 M in Et2O (11 mL, 22 mmol) is slowly added dropwise, and stirring is continued
for 4h. Excess of Grignard reagent is quenched with diluted aqueous HCl. Extraction with 136 | Chapter 6
Et2O (3 x 150 mL), washing the extract with H2O (2 x 200 mL), drying with Na2SO4,
filtration, evaporation of the solvent and purification by vacuum distillation yielded 2.18 g
1 (71%) as a colorless oil, bp. 65-68 °C/17 mbar. H NMR (400 MHz, CDCl3) δ 4.71 – 4.68 (m,
3 2 3 2H), 2.00 (td, JHH = 7.8 Hz and JHH = 3.0 Hz, 4H), 1.50 – 1.20 (m, 10H), 0.90 (td, JHH =
2 13 7.2 Hz and JHH = 5.4 Hz, 6H). C NMR (101 MHz, CDCl3) δ 150.56, 108.47, 36.22, 35.95,
31.85, 30.21, 27.68, 22.76, 22.71, 22.68, 14.22, 14.16. MS (EI): 154 (14, [M]+), 97 (13), 84 (12),
+ 70 (37), 56 (100), 43 (15). HRMS (EI, ([M] )): m/z calcd for C11H22 154.1716; Found 154.1721.
Potassium bis(ethyleneglycolato)borate. The title compound was prepared following a
reported procedure.29 A white poorly soluble solid, was formed. 1H NMR (500 MHz, DMF-
11 11 d7) δ 3.55 (s, 2H), 3.13 (s, 1H). B NMR (160 MHz, DMF-d7) δ 11.24. B NMR (160 MHz,
DMF-d7: EG-d6 (16:1)) δ 10.55, 7.00. Elemental analysis indicates that some K2CO3 precipitate with the product. Elemental analysis: Anal. Calcd for C4.93H8BK2.86O6.79
(C4H8O4BK+0.93 K2CO3): C, 19.83; H, 2.70. Found: C, 19.82; H, 2.70.
6.5. Reactivity of complexes 2.4 and 2.4Na towards R–X
Representative procedure with in situ made 2.4. To a dark red solution of 1.4a (37.3
mmol) or a mixture of (1.4aNa (37.3 mmol) and dry CF3COOH (37.3 mmol)) in anhydrous
DMA (2 mL) and Pd(dba)2 (41.0 mmol) under inert atmosphere at room temperature was
added an excess of R–X (from 1.1 to 100 equiv.). A change in the color of the reaction is
observed when the oxidative addition takes place. 31P NMR were taken after 30 min. No
reaction was observed for R–X = PhI or 4-nitrobenzyl-4-nitrobenzenesulfonate. For R–X =
4-benzenediazoniumsulfonate: 31P NMR (121 MHz, DMA) δ 20.78.
Representative procedure with in situ made 2.4Na. Same procedure as above using
1.4aNa (37.3 mmol) without an additional acid. 31P NMR were taken after 30 min. For R–
X = 4-nitrobenzyl-4-nitrobenzenesulfonate: 31P NMR (121 MHz, DMA) δ 33.03 (s, phosphonium salt) and 24.67 (s) in a 1/9 ratio in favor of the desired product. For R–X =
PhI: 31P NMR (121 MHz, DMA) δ 8.77, and a fraction of the reaction mixture was diluted in DCM and immediately used for gas phase studies in the negative mode. Experimental | 137
Figure 6.1. Full scan in the negative mode. The product of the oxidative addition of phenyl iodide is observed.
The complexes 2.9 and 1.5b were prepared from benzyl bromide and methyl iodide,
respectively in THF following a procedure similar to that described above. In both cases, the
presence of a phosphonium salt was observed in the 31P NMR. Spontaneous formation of the
31 crystals of 2.9 was observed: P NMR (121 MHz, THF-d8) δ 32.77 (s, phosphonium) and
18.04 (s, complex), 10/1 ratio. The product of the oxidative addition of MeI was not isolated:
31 P NMR (122 MHz, THF-d8) δ 28.18 (s, phosphonium), 16.18 (s, complex), 10/1 ratio. The
halide abstraction was done at ambient temperature on the product of the oxidative addition
31 of MeI in THF. P NMR (122 MHz, THF-d8) δ 28.18 (s, phosphonium), 27.41 (s, Pd
complex), 10/1 ratio. THF was evaporated and washed several time with Et2O and dried
under vacuum. The resulting residue was dissolved in a mixture of DCM/MeCN (5/1) and
recrystallized by diffusion of Et2O at room temperature to give light yellow crystals. The
crystals washed with pentane and dried under high vacuum. MeCN signal does not appear
1 on the proton NMR. H NMR (400 MHz, CDCl3) δ 8.21 – 8.15 (m, 1H), 7.66 – 7.53 (m, 2H),
7.49 (ddt, J = 9.1, 8.2, 1.3 Hz, 2H), 7.46 – 7.39 (m, 1H), 7.26 – 7.17 (m, 2H), 7.01 (tt, J = 138 | Chapter 6
7.7, 1.1 Hz, 2H), 6.90 (ddd, J = 8.4, 4.8, 1.1 Hz, 2H), 3.62 (s, 6H), 0.35 – 0.16 (m, 3H). 31P
NMR (162 MHz, CDCl3) δ 21.54 (brs).The crystals were later used for the regeneration
reaction in the presence of MA.
6.6. Polymerization experiments
Representative polymerization of MA in the presence of radical initiator and
radical trap. In a glove box, under an inert atmosphere, benzene diazonium chloride (0.012
g, 88 µmol, 1.1 equiv.) was placed into a 10 mL screw-cap vial. To this was added PPh3 (0.021 g, 80 µmol, 1.0 equiv.), BHT (125 mg) followed by 3.2 mL of toluene and 1.8 mL of methyl
acrylate. The vial was closed and the reaction mixture stirred at 60 °C for 4 h. The reaction
mixture was cooled to room temperature, diluted with AcOEt and filtered over Celite. The solvents were removed under vacuum and Et2O was added to precipitate the polymers. The
obtained viscous poly methyl acrylate were washed with MeOH and dried under high vacuum
at 80 °C. 883 mg of polymers were obtained. Mw = 99’262, Mw/Mn = 4.3.
Representative polymerization of MA using 1.5a.30 An 10 mL screw-cap vial was
charged with 5 mL of an MA solution in toluene (4 mol L-1), 125 mg of BHT, and 48 mg (80
μmol) of 1.5a. The mixture was stirred at 95°C for 4 h. After the indicated time, the reaction
mixture was cooled to room temperature and the work-up was done according to the
procedure described above. Traces of polymers (<40 mg) were obtained.
Representative polymerization of MA using (1,5-cyclooctadiene)PdMeCl.31 In a glove box, under an inert atmosphere, (1,5-cyclooctadiene)PdMeCl (0.021 g, 80 µmol,
1.0 equiv.) was placed into a 10 mL screw-cap vial. To this was added PPh3 (0.021 g, 80 µmol,
1.0 equiv.) followed by 3.2 mL of toluene or dichloromethane, and the mixture was gently
swirled to dissolve the starting materials, thus forming a clear, colorless solution. Next, 1.8 mL
of methyl acrylate was added to the solution, the vial was closed and the reaction stirred at
50° C for 4 h to 24 h. The polymerizations were done with and without BHT (125 mg). The
work-up was done according to the procedure described above. Experimental | 139
Representative polymerization of Ethylene using 1.5a in the presence or absence
of radical trap. In the glovebox, the catalyst 1.5a (0.024 g, 40 µmol) was weighed into a
stainless steel autoclave. Anhydrous toluene (50 mL) was added. For the polymerization done
in the presence of radical trap, Galvinoxyl (0.084 g, 200 µmol) was also added. The liner was
placed in the autoclave, and the autoclave was assembled, brought out of the box, and hooked
to the controller and to an ethylene delivery system. The reactor was heated and stirred at
80-85 °C for 1 h. The mixture was cooled to room temperature, and the polymers were
collected by filtration, washed with boiling toluene, acetone, and hexanes. Powdery white
polyethylene was obtained.
6.7. Cyclopropanation experiments
Representative methylenation procedure in DMA/EG or THF/EG. An oven-dried
Schlenk (2.5 or 5 mL) equipped with a Teflon Young valve and an oven-dried magnetic stir bar was charged in a N2-filled glovebox with powdered K2CO3 (80.9 mg, 5.0 equiv.) and
anhydrous ethylene glycol (EG, 0.1 mL). The mixture was vigorously stirred for 10 min
before, and during, the addition of a solution of anhydrous dimethylacetamide (DMA, 0.6
mL) containing Pd-catalyst [(o-tolyl)3P]2PdCl2 (4.6 mg, 5 mol%), ICH2BF3K (34.8 mg, 1.2
equiv.) and cyclooctene (COE, 15.2 µL, 0.117 mmol). The rest of the anhydrous DMA (2 x
0.5 mL) was utilized to rinse the vial containing the previous solution and then added to the
reaction mixture. The tube was sealed, removed from the glovebox, and heated to 75 °C for
22 h. The reaction mixture was then rapidly cooled to 0 °C in an ice bath for 15 min and a
work-up was conducted.
Representative methylenation procedure in DMA/MeOH. A 5 mL oven-dried
Schlenk (2.5 or 5 mL) equipped with a Teflon Young valve and an oven-dried magnetic stir bar was charged in a N2-filled glovebox with powdered K2CO3 (80.9 mg, 5.0 equiv.) and
anhydrous MeOH (0.5 mL). The mixture was vigorously stirred for 10 min before, and during,
the addition of a solution of anhydrous DMA (0.6 mL) containing Pd-catalyst [(o-
tolyl)3P]2PdCl2 (4.6 mg, 5 mol%), ICH2BF3K (34.8 mg, 1.2 equiv.) and COE (15.2 µL, 0.117 140 | Chapter 6
mmol). The rest of the anhydrous DMA (2 x 0.5 mL) and anhydrous MeOH (0.3 mL) was
utilized to rinse the vial containing the previous solution and then added to the reaction
mixture. The tube was sealed, removed from the glovebox and heated to 75 °C for 22 h. The
reaction mixture was then rapidly cooled to 0 °C in an ice bath for 15 min and a work-up
was conducted.
Procedure for small-scale work-up. The internal standard, undecane (10 μL, around 0.40
equiv. for 0.117 mmol scale of olefin), was added to the tube with the reaction mixture,
followed by Et2O (2 x 35 mL/mmol substrate). The solution was transferred to a 15 mL glass
vial. The Schlenk tube was rinsed with H2O (45 mL/mmol substrate) or saturated NH4Cl for the allylic alcohols. The aqueous layer was transferred to the 15 mL glass vial and the layers were separated. The organic phase was transferred to another 15 mL glass vial, washed with
H2O (45 mL/mmol substrate) and brine (45 mL/mmol substrate), dried over MgSO4, and
then filtered through Celite. The resulting solution was analyzed by GC–FID.
6.8. Kinetic Experiments
6.8.1. NMR monitoring kinetic experiment for the β-hydride elimination
Procedure. An oven-dried NMR tube was transferred into a N2-filled glovebox and charged with 7.4 mg (11 µmol) of complex 2.8b and 5.5 mL of fresh anhydrous TCE-d2 (2.0 mM), sealed and the 1H NMRs were recorded at indicated temperatures.
6.8.1. Kinetic experiment at 85 °C
Experimental | 141
Table 6.1. Results of the 1H NMR monitoring reaction at 85 °C.
Time [s] 2.8b conc. [mM] 1/conc. [Mm-1]
0 2 0.500 321.48 1.788 0.559 642.95 1.713 0.584 964.43 1.660 0.602 1285.90 1.600 0.625 1607.38 1.575 0.635 1928.85 1.525 0.656 2250.33 1.475 0.678 2571.80 1.438 0.696 3214.75 1.375 0.727 3857.70 1.325 0.755 4500.65 1.250 0.800 5143.60 1.213 0.825 5786.55 1.175 0.851 7072.45 1.100 0.909 8358.35 1.025 0.976 9644.25 0.950 1.053 10930.15 0.900 1.111 12216.05 0.850 1.176 13501.95 0.800 1.250 14787.85 0.763 1.311 16073.75 0.725 1.379 17359.65 0.675 1.481
142 | Chapter 6
Figure 6.2. Evolution of the concentration of the catalyst 2.8b with time at 85 °C and reaction rate for the degradation of the catalyst 2.8b at 85 °C in TCE-d2.
6.8.1. Kinetic experiment at 105 °C
Table 6.2. Results of the 1H NMR monitoring reaction at 105 °C.
Time [s] 2.8b conc. [mM] Ln(conc.)
0 2 0.693147 402.98 1.55003 0.438274 604.47 1.26669 0.236407 805.96 1.13336 0.125187 1007.45 1.00002 2·10-5 1208.94 0.85002 -0.1625 1410.43 0.80002 -0.22312 1611.92 0.70001 -0.35666 1813.41 0.61668 -0.48341 2216.39 0.53334 -0.6286 2619.37 0.41668 -0.87544 3022.35 0.36667 -1.00329 3425.33 0.28334 -1.26111 4231.29 0.18334 -1.69641
Experimental | 143
Figure 6.3. Evolution of the concentration of the catalyst 2.8b with time at 105 °C.
6.8.2. Kinetic experiments for the cyclopropanation of alkenes
Procedure. Each time point in a kinetic run was acquired with the following procedure. An
oven-dried Schlenk (2.5 or 5 mL) equipped with a Teflon Young valve and an oven-dried
magnetic stir bar was charged in a N2-filled glovebox with powdered K2CO3 (80.9 mg, 5.0 equiv.) and anhydrous EG (0.1 mL). The mixture was vigorously stirred for 10 min before, and during, the addition of a solution of anhydrous DMA (0.6 mL) containing either the Pd- catalyst [(o-tolyl)3P]2PdCl2 (4.6 mg, 5 mol%) or the mixture of (o-tolyl)3P (1.78 mg, 5 mol%)
and the Pd-catalyst [COD]PdCl2 (1.67 mg, 5 mol%), ICH2BF3K (34.8 mg, 1.2 equiv.) and
COE (15.2 µL, 0.117 mmol). The rest of the anhydrous DMA (2 x 0.5 mL) was utilized to rinse the vial containing the previous solution and then added to the reaction mixture. The tube was sealed, removed from the glovebox and heated to 75 °C for the indicated reaction time. Then the reaction mixture was rapidly cooled to 0 °C in an ice bath for 15 min and a work-up was conducted. The resulting solution was analyzed by GC-FID.
144 | Chapter 6
6.8.2.1. Influence of ICH2BF3K
Table 6.3. Initial concentrations of ICH2BF3K and excess to determine its influence on the reaction rate.
Run ICH2BF3K [mM] ICH2BF3K [mM] Excess [mM] 1 0.117 0.069 0 2 0.140 0.082 0.013 Table 6.4. Results from the kinetic runs based on Table 6.3.
Run 1 Run 2
Time [min] COE rem. [mg] COE conc. [10-2 mM] COE rem. [mg] COE conc. [10-2 mM] 0 12.89 6.88 12.89 6.88 30 11.80 6.30 12.20 6.51 60 10.09 5.39 10.33 5.51 90 8.52 4.55 8.69 4.64 120 7.65 4.09 7.38 3.94 150 6.03 3.22 6.01 3.21 180 5.34 2.85 4.84 2.58 210 4.11 2.19 4.03 2.15 240 3.47 1.85 3.21 1.72 270 3.11 1.66 2.22 1.18 300 3.03 1.62 1.88 1.00 360 2.93 1.56 1.44 0.77
6.8.2.2. Influence of the olefin COE
Table 6.5. Initial concentrations of COE and excess to determine its influence on the reaction rate.
Run COE [mM] COE [mM] Excess [mM] 1 0.117 0.069 0 2 0.140 0.082 0.013
Table 6.6. Results from the kinetic runs based on Table 6.5.
Experimental | 145
Run 1 Run 2
Time [min] COE rem. [mg] COE conc. [10-2 mM] COE rem. [mg] COE conc. [10-2 mM] 0 12.89 6.88 15.52 6.90 30 11.80 6.30 13.91 6.19 60 10.09 5.39 11.96 5.32 90 8.52 4.55 10.13 4.51 120 7.65 4.09 8.42 3.75 150 6.03 3.22 6.93 3.08 180 5.34 2.85 6.29 2.80 210 4.11 2.19 5.79 2.58 240 3.47 1.85 5.48 2.44 270 3.11 1.66 5.12 2.28 300 3.03 1.62 4.91 2.18 360 2.93 1.56 4.81 2.14
6.8.2.3. Influence of catalyst loading
Table 6.7. Initial catalyst loadings to determine its influence on the reaction rate.
Run Catalyst loading [mol%] 1 5 2 10 Table 6.8. Results from the kinetic runs based on Table 6.7. Run 1 Run 2
Time [min] COE rem. [mg] COE conc. [10-2 mM] COE rem. [mg] COE conc. [10-2 mM] 0 12.89 6.88 12.89 6.88 30 11.80 6.30 11.59 6.18 60 10.09 5.39 9.24 4.93 90 8.52 4.55 7.18 3.84 120 7.65 4.09 5.35 2.86 150 6.03 3.21 4.64 2.47 180 5.34 2.85 4.12 2.20 210 4.11 2.19 3.61 1.93 240 3.47 1.85 3.10 1.65 270 3.11 1.66 2.80 1.50 300 3.03 1.62 2.52 1.35 360 2.93 1.56 2.34 1.25 146 | Chapter 6
6.8.2.4. Influence of the co-solvent concentration
Table 6.9. Initial solvents ratios (and volumes) to determine the influence EG on the reaction rate.
Run DMA:EG ratio (volumes [mL]) 1 16:1 (1.6:0.1) 2 32:1 (1.6:0.05)
Table 6.10. Results from the kinetic runs based on Table 6.9.
Run 1 Run 2
Time [min] COE rem. [mg] COE conc. [10-2 mM] COE rem. [mg] COE conc. [10-2 mM] 0 12.89 6.88 15.52 7.09 30 11.80 6.30 11.42 6.28 60 10.09 5.39 9.11 5.01 90 8.52 4.55 7.21 3.96 120 7.65 4.09 6.21 3.42 150 6.03 3.21 4.93 2.71 180 5.34 2.85 4.05 2.22 210 4.11 2.19 10.03 2.01 240 3.47 1.85 10.75 1.92 270 3.11 1.66 11.02 1.82 300 3.03 1.62 11.30 1.56 360 2.93 1.56 11.08 1.47
6.8.2.5. Influence of the phosphine ligand
Table 6.11. Initial equivalences of phosphine ligand to determine its influence on the initial reaction rate.
Run (o-tolyl)3P [equiv.] [COD]PdCl2 [mol %] 1 1 5 2 2 5
Experimental | 147
Table 6.12. Results from the kinetic runs based on Table 6.11.
Run 1 Run 2
Time [min] COE rem. [mg] COE conc. [10-2 mM] COE rem. [mg] COE conc. [10-2 mM]
0 12.89 6.88 12.89 6.88
60 9.56 5.10 8.97 4.79
90 7.87 4.20 7.92 4.23
120 6.71 3.58 6.24 3.33
6.9. Procedure for the NMR monitoring methylenation reaction of COE
An oven-dried NMR tube equipped with a Teflon screw cap was transferred into a N2-filled glovebox and charged with powdered K2CO3 (0.195 mmol, 5.0 equiv.). A 1.5 mL oven-dried
vial was charged with [(o-tolyl)3P]2PdCl2 (1.53 mg, 5 mol%), ICH2BF3K (9.67 mg, 1.2 equiv.)
and COE (5.1 µL, 0.039 mmol), anhydrous EG-d6 (0.33 mL) and anhydrous DMA-d9 (2.33
mL). The solution was then transferred to the NMR tube and the vial rinsed with anhydrous
DMA-d9 (2 x 1.5 mL). The rinse solution was added to the NMR tube. The NMR tube was
sealed, shaken, and maintained at 75 °C for 16 h. 60.3% GC yield of cyclopropane formed.
6.10. Procedure for the oxidative addition of ICH2Bpin in THF
An oven-dried NMR tube was brought into a N2-filled glovebox and charged with Pd(dba)2
(30 mg, 0.052 mmol, 1.05 equiv.), (o-tolyl)3P (15 mg, 0.049 mmol, 1.0 equiv.), and anhydrous
THF-d8 (0.4 mL). The tube was then closed and agitated for ∼5 min. A 1.5 mL oven-dried
vial was charged with ICH2Bpin (33 mg, 0.123 mmol, 2.5 equiv.) and anhydrous THF-d8 (0.2 mL). The solution was then transferred to the NMR tube. The tube was closed with a cap and agitated for 15 min, and NMR was taken at room temperature. The dark red solution
31 turned yellow with deposit of a greenish solid. P NMR (202 MHz, THF-d8) δ 32.25, 31.25,
11 27.13, 22.69, -30.39. B NMR (160 MHz, THF-d8) δ 31.71, 22.46.
Gas phase studies. In the glovebox, 0.1 mL of the reaction mixture was diluted to ∼10-5 M in dry MeCN or dry THF and use immediately for gas phase studies. Conditions: spray voltage: 5 kV, collision offset: 35 V, tube lens offset: 100 V and capillary temperature: 50 °C 148 | Chapter 6
or 170 °C. Collision-induced dissociation (CID) experiments were done with an argon pressure
of 0.5 mTorr in the collision cell.
6.11. Procedure for the oxidative addition of ICH2Bpin in the presence of NBE in THF
An oven dried NMR tube was transferred into a N2-filled glovebox and charged with Pd(dba)2
(30 mg, 0.052 mmol, 1.05 equiv.), (o-tolyl)3P (15 mg, 0.049 mmol, 1.0 equiv.) and anhydrous
THF-d8 (0.4 mL). The tube was closed and agitated for ∼5 min. NBE (23.07 mg, 0.245 mmol,
5 equiv.) in anhydrous THF (0.2mL) was added and an NMR of the resulting orange solution was taken 30 min later. The tube was then transferred back to the glovebox and charged with
ICH2Bpin (33 mg, 0.123 mmol, 2.5 equiv.). Another NMR was taken and the mixture was
heated to 60 °C for 10 min and cooled to room temperature, diluted and use immediately for
gas phase studies.
6.12. Procedure for the oxidative addition of ICH2BF3K in DMF
An oven-dried NMR tube was brought into a N2-filled glovebox and charged with the Pd
complex t-BuXPhos Pd G3 (4.8 mg, 6.0 μmol, 1.0 equiv.), ICH2BF3K (3.0 mg, 1.2 μmol, 2.0
equiv.) and powdered K2CO3 (1.7 mg, 1.2 μmol, 2.0 equiv.), successively dissolved in
anhydrous DMF-d7 (0.6 mL). The tube was then closed and agitated for ∼5 min and NMR
1 was taken at room temperature. H NMR (400 MHz, DMF-d7) δ 11.26 (s, 1H, carbazole NH),
3 8.22 – 8.18 (m, 1H, Pd complex aryl CH), 8.17 (d, JHH = 7.8 Hz, 2H, carbazole CH), 7.71 –
3 7.63 (m, 2H, Pd complex aryl CH), 7.55 (d, JHH = 8.2 Hz, 2H, carbazole CH), 7.44 – 7.37
(m, 2H, carbazole CH), 7.36 (s, 2H, Pd complex aryl CH), 7.28 – 7.23 (m, 1H, Pd complex
3 aryl CH), 7.21 – 7.15 (m, 2H, carbazole CH), 3.48 (s, H2O), 2.98 (hept, JHH = 6.9 Hz, 1H,
3 – Pd complex i-Pr CH), 2.46 (hept, JHH = 6.7 Hz, 2H, Pd complex i-Pr CH), 2.42 (s, CH3SO3
– 3 ), 1.83 (s, ICH2BF3 ), 1.55 (d, JHH = 6.7 Hz, 6H, Pd complex i-Pr CH3),
3 3 1.48 (d, JHP = 15.1 Hz, 18H, Pd complex t-Bu), 1.32 (d, JHH = 6.9 Hz, 6H, Pd complex i-
– 3 Pr CH3), 1.16 – 1.08 (m, 2H, PdCH2BF3 ), 0.95 (d, JHH = 6.5 Hz, 6H, Pd complex i-Pr CH3).
31 4 19 P NMR (122 MHz, DMF-d7) δ 75.49 (q, JPF = 32.1 Hz). F NMR (282 MHz, DMF-d7) δ - Experimental | 149
– 2 – 139.21 (s, PdCH2BF3 ), -143.55 (m, JFB = 48.6 Hz, ICH2BF3 ), -151.24. The mixture was
diluted in THF and immediately use for gas phase studies.
6.13. Cyclopropanation of COE - Control experiments
The methylenation procedures were followed and only the reagents needed for each
experiment were charged in the oven-dried Schlenk tube. The tube was sealed, removed from
the glovebox and heated to 75 °C for 16 h. At the end of the indicated time, the Schlenk tube
was cooled to 0 °C for 15 min, dried and transferred to the glovebox. 0.6 mL of the solution
were filtered and transferred into an oven-dried NMR tube placed in an external NMR tube
containing the reference solvent DMF-d7. The tubes were closed and NMR was taken at room
temperature.
6.13.1. Cyclopropanation of COE
Two reactions were performed separately. The work up procedure is done for one in order to
get the GC yield and the other reaction is submitted for spectroscopic observations. The
reaction mixture was dark grey due to the decomposition of the Pd catalyst. The cyclopropane
was formed in 88%. Only free ligand observed in the 31P NMR spectrum. 11B NMR (160 MHz,
2 19 DMF-d7) δ 10.55, 7.03, 2.46 (q, JBF = 49.5 Hz), -0.96. F NMR (470 MHz, DMF-d7) δ -
2 31 143.39 (m, JFB = 48.3 Hz), -150.76 – -151.54 (m). P NMR (202 MHz, DMF-d7) δ -30.40.
6.13.2. Cyclopropanation of COE in the absence of olefin
150 | Chapter 6
The final mixture was orange at the end of the indicated time and no black precipitate was
31 11 present. P NMR (202 MHz, DMF-d7) δ 40.44, 35.64, -30.40. B NMR (160 MHz, DMF-d7)
2 19 δ 10.51, 8.75, 7.00, 2.44 (q, JBF = 48.9 Hz), -0.97. F NMR (470 MHz, DMF-d7) δ -132.45, -
2 138.32, -140.40, -143.54 (m, JFB = 47.0 Hz), -151.25.
The catalyst is still active in the absence of the olefin, but the amount of the methylene
transfer agent is reduced.
6.13.3. COE added 16 h later to the reaction mixture
6.13.4. ICH2BF3K added 16 h later to the reaction mixture
Cat1 (5 mol%) I BF3K K2CO3 (5.0 equiv.) (1.2 equiv.) Black deposit No product DMA/EG (16/1) 75 °C, 24 h (1.0 equiv.) 75 °C, 16 h 1a
6.14. References
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8434–8451.
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Gamble Company). Perfume Systems, WIPO Patent WO2012177357 A1, May 24, 2012.
22 Charette, A. B.; Beauchemin, A. Org. React. 2001, 58, 1–415.
23 O’Connor, E. J.; Brandt, S.; Helquist, P. J. Am. Chem. Soc. 1987, 109, 3739–3746.
24 McKee, M.; Haner, J.; Carlson, E.; Tam, W. Synthesis 2014, 46, 1518–1524.
152 | Chapter 6
25 Seitz, D. E.; Zapata, A. Tetrahedron Lett. 1980, 21, 3451–3454.
26 Lebel, H.; Davi, M.; Díez-González, S.; Nolan, S. P. J. Org. Chem. 2007, 72, 144–149.
27 Ohta, H.; Kobayashi, N.; Ozaki, K. J. Org. Chem. 1989, 54, 1802–1804.
28 Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L. Synthesis 1987, 11, 1034–1036.
29 Cunningham, P. H.; Warren, L. F. Jr.; Marcy, H. O.; Rosker, M. J. (Rockwell International
Corporation). Semi-organic crystals for nonlinear devices. Eur. Pat. Appl. 0693704, 1996.
30 Guironnet, D.; Roesle, P.; Ruenzi, T.; Göttker-Schnetmann, I.; Mecking, S. J. Am.
Chem. Soc. 2009, 131, 422–423.
31 Sen, A.; Kacker, S.; Hennis, A.; Polley, D. J. Palladium (II) Catalyzed
Polymerization of Norbornene and Acrylates, U.S. Patent 6,111,041, August 29, 2000.
Appendix A
Annexes
7.1. Crystallography data
7.1.1. X-ray structure of 4.8a
Figure 7.1. Crystal structure of complex 4.8b at 30% thermal ellipsoids. Solvents are omitted for clarity. Selected bond lengths (Å) and angle (deg) of 4.8b: Pd1b−P1b = 2.296(2); Pd1b−Clb1 = 2.351(2); Pd1b−Cl2b = 2.3546(19); Pd1b−P2b = 2.294(2); P2b−Pd1b−Cl1b = 166.71(8); P2b−Pd1b−Cl1b = 166.71(8); Cl1b−Pd1b−Cl2b = 90.03(7); P1b−Pd1b−P2b = 104.03 (7).
154 | Appendix A
2 S 2 Pd 2 P
13 13 25 25 19 19 10 ≤ ≤ ≤ O = 0.0731] = 0.0731] 2 l k h ≤ N ≤ ≤ int = 0.0920 = 0.1042 4 2.16b 2 2 = 0.0487 = 0.0487 = 0.0962 1 1 Cl 70 = 28.39 : 99.5% = 28.39 H θ 54 12 12 -13 19 19 -26 27 -19 PPdS C
≤ ≤ 5 ≤ = 0.046] [R 6748 1)/c P 1 2(1)/c 1 l k h int NO ≤ ≤ ≤ 2.14 = 0.1292 = 0.1292 wR = 0.1114 0.1114 = wR 26 2 2 = 0.0388 = 0.0388 R = 0.0547 = 0.0547 R 1 1 H 28 = 30.02: 90.9% 90.9% = 30.02: θ PPdS C PPdS 18 18 -13 13 13 -20 5 22 22 -27
≤ ≤ ≤ = 0.0228] = 0.0228] 7011 [R l k h ≤ ≤ ≤ int 2.13 = 0.0529 = 0.0539 wR wR ClNO 2 2 = 0.0212 = 0.0212 R = 0.0198 = 0.0198 R 1 1 23 H 25 = 27.485 : 100% = 27.485 θ PPdS C PPdS 10 15 15 -18 18 18 -13 20 -22 ≤ ≤
≤ = 0.0438] 0.0438] = 5606 [R l k h int 2.9 ≤ ≤ ≤ = 0.1578 = 0.1802 wR wR 2 2 = 0.0510 = 0.0510 = 0.0771 R R BrNaO 1 1 65 H = 28.39 : 99.4% = 28.39 47 θ parameters for all X-ray structures X-ray for all parameters 11 11 -15 14 14 -16 17 17 -20 PPdS C
≤ ≤ 8 ≤ = 0.0353] = 0.0353] 10987 [R 2 2 4 4 2 4 2 l k h 772 1100 1256 1272 1420 1256 772 1100 P-1 P-1 P 2(1)/c P 2( NO int ≤ ≤ ≤ 1.470 1.602 1.689 1.576 1.470 1.602 1.689 1.58 1.256 1.306 1.087 0.897 1.256 1.306 1.087 1.110 0.707 1.483 1.057 0.883 0.883 0.707 1.483 1.057 0.988 = 0.0932 = 0.0932 wR = 0.0992 wR 26119 77110 67850 18270 26119 77110 67850 25068 748.10 1062.32 748.10 1062.32 625.96 622.32 1387.87 40 2 2 = 0.0377 = 0.0377 R = 0.0516 = 0.0516 R 100.0(2) 100.0(2) 100.0(2) 100.0(2) 100.0(2) 100.0(2) 100.0(2) 100.0(2) 100.0(2) Triclinic Triclinic Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic Triclinic Triclinic 1 1 14.993(3) 15.2843(11) 15.2843(11) 14.993(3) 19.5113(6) 17.444(4) 14.8032(5) 10.639(2) 11.5492(9) 9.5913(2) 13.867(3) 10.3801(4) 14.3412(4) 13.7428(9) 11.351(2) 10.624(3) 19.9745(8) 92.524(5) 106.293(3) 106.293(3) 92.524(5) 90 90 90 1692.6(6) 2201.8(3) 2447.0(10) 2638.65(12) 2638.65(12) 2447.0(10) 1692.6(6) 2201.8(3) 90 91.089(5) 92.163(4) 107.801(4) 100.5239(11) 108.826(2) 108.826(2) 100.5239(11) 107.801(4) 91.089(5) 92.163(4) H 110.545(5) 107.432(3) 110.545(5) 107.432(3) 90 90 2905.06(19) -19 R R -10 -13 -13 1.92 to 27.69 to 27.69 1.92 to 28.39 1.40 to 54.97 3.084 30.03 2.75 to 27.65 1.78 to 33 wR wR 1.169 & -1.051 2.278 & -1.378 0.60 & -0.67 0.565 & -1.071 1.667 & -1.950 7652 / 0 7652 / 415 50 539 10987 / 318 5606 0 / / 438 7011 0 / / 9 372 6748 / = 27.69 : 96.7% 0.9588 & 0.8715 0.9295 & 0.7173 0.746 & 0.690 0.945 & 0.805 0.9805 & 0.8907 C 0.20 x 0.06 x 0.16 0.24 x 0.05 0.1 × × 0.24 0.32 x 0.12 0.42 x 0.06 0.020 x 0.040 0.120 θ 7652 [R ] 3 (I)] (I)] ] σ 3 ] ]
2 -3 -1 ] ] ll data) -1 3 [°]
[°] [°] Z
[°] [°] [Å] [Å] [Å] [Å] [Å] β γ α b c a [mg m [mg T [K] [K] T V [Å F(000) µ [mm calc GOF on F GOF on space group space group FW [g mol ρ Crystal system system Crystal Limiting indices Completeness to Empirical formula Crystal size [mm size Crystal Identification code code Identification 2.8b R indices (a Reflections collected Independent reflections Final R indices [I>2 Max. & min. transmission transmission & min. Max. range for [°] range for data collection Data/restraints/parameters θ Largest diff. peak & hole [eÅ 7.1.2. Data collection and refinement collection and Data 7.1.2.
Annexes | 155
2 Pd 4 P 2 24 17 17 29 ≤ ≤ ≤ Fe = 0.1480] = l k 13 h int ≤ ≤ ≤ = 0.1738 = 0.1931 Cl 2 2 = 0.0720 = 0.1025 1 1 75 H 79 = 66.838 : 96.5% : 96.5% = 66.838 θ 16 16 -24 13 13 -17 PPd C 24 24 -20 3 ≤ ≤ ≤ = 0.0696] [R 13533 l BF k h ≤ ≤ ≤ int 47 = 0.0714 = 0.0800 wR wR .3337(6) 14.7588(8).3337(6) 2 2 = 0.0409 = 0.0409 = 0.0712 R R H 1 1 30 = 27.553 : 99.3% : 99.3% = 27.553 θ PPdS C PPdS 14 14 -19 21 -12 5 17 17 -24 ≤ ≤ ≤ = 0.0506] [R 6663 NO l k h 2 ≤ ≤ ≤ int = 0.0762 wR = 0.0795 wR F 2 2 = 0.0413 = 0.0413 R = 0.0559 R 1 1 24 2.16c-pyr 3.12 4.8b H = 27.51 : 99.5% 26 θ C 2 S 2 Pd 2
P 16 16 -14 15 -21 29 -17 14 ≤ ≤ ≤ O = 0.0366] = 0.0366] [R 5784 2 2 4 4 4 4 2 4 l k h 90 90 90 90 90 90 90 90 90 90 90 90 ≤ N ≤ ≤ int 1612 1288 1280 3896 3896 1280 1612 1288 1.527 1.676 1.404 1.628 1.404 1.527 1.676 1.204 1.401 1.033 1.169 1.169 1.033 1.401 1.204 0.857 0.934 0.732 11.672 0.732 0.857 0.934 = 0.0625 wR = 0.0591 wR 54858 21459 23002 6478 23002 54858 21459 4 100(2) 100(2) 100.0(2) 100.0(2) 100.0(2) 100.0(2) 100(2) 100(2) 2 2 = 0.0253 = 0.0253 = 0.0354 R R 1563.99 637.89 612.85 1933.62 1933.62 612.85 637.89 1563.99 1 1 97.086(3) 97.661(2) 91.386(3) 94.009(4) 91.386(3) 97.661(2) 97.086(3) 3402.5(4) 2528.1(3) 2898.9(3) 7888.9(8) 2898.9(3) 2528.1(3) 3402.5(4) Cl 12.7457(9) 11.3661(9) 14.9955(10) 20.8947(13) 20.8947(13) 14.9955(10) 11.3661(9) 12.7457(9) 10 11.8796(7) 16.8680(11) Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic -29 22.6448(15) 13.3049(11) 18.7133(12) 25.6445(14) 25.6445(14) 18.7133(12) 13.3049(11) 22.6448(15) R R -15 -16 P 1 2(1)/c 1 P 1 21/n 1 P 21/c P 21/c 2.35 to 27.58 2.35 to 27.51 2.22 9.568 to 55.106 7.852 to 133.676 86 wR wR 0.446 & -0.433 0.973 & -0.930 0.55 & -0.56 2.01 &-1.74 7859 / 6 589 5784 / 1 / 419 6663 / 0 / 337 13533 / 78 / 946 = 27.58 : 99.6% 0.9346 & 0.7831 & 0.7831 0.9346 0.9725 & 0.8209 & 0.669 0.734 & 0.174 0.381 H θ 7859 [R 62 0.080 x 0.120 x 0.300 x 0.140 0.220 0.030 0.09 × 0.06 0.01 0.190.01 × 0.12 C ] 3 (I)] (I)] ] σ 3 ] ]
2 -3 -1 ] ] ll data) -1 3 [°]
[°] [°] Z
[°] [°] [Å] [Å] [Å] [Å] [Å] [Å] β α γ b c a [mg m [mg T [K] [K] T V [Å F(000) µ [mm calc GOF on F GOF on space group space group FW [g mol ρ Crystal system system Crystal Limiting indices Completeness to Empirical formula Crystal size [mm size Crystal Identification code code Identification 2.16e R indices (a Reflections collected Independent reflections Final R indices [I>2 Max. & min. transmission transmission & min. Max. range for [°] range for data collection Data/restraints/parameters θ Largest diff. peak & hole [eÅ
156 | Appendix A
7.2. In situ generation of 2.6b
1 Figure 7.2. H NMR spectra of in situ-generated 2.6b in DMF-d7.
1 Figure 7.3. H NMR spectra of in situ-generated 2.6b in CD2Cl2.
Annexes | 157
7.3. In situ catalyst regeneration with phenyldiazonium tosylate
O
O
methyl cinnamate
Figure 7.4. Representative GC chromatogram of the in situ regeneration of the catalyst during in the oligomerization reaction of MA. Retention times: methyl cinnamate (tR= 12.64 min), dodecane (tR= 10.04 min; internal standard). 158 | Appendix A
7.4. Cartesian coordinates, total energies, and imaginary frequencies (for transition states)
C -2.13266600 0.00000000 0.01636400 C -1.13314500 0.78834000 0.67972700 C 0.24617600 -1.14123500 0.34104000 H -1.98136400 0.99792400 1.34041500 C 0.24617600 1.14123500 0.34104000 C -1.13314500 0.78834000 -0.67972700 C 0.27119400 0.00000000 1.39067900 H -1.98136400 0.99792400 -1.34041500 H 1.20317200 0.00000000 1.98355000 C 1.13537300 0.80027600 0.00000000 H -0.58144900 0.00000000 2.08854100 H 2.14879100 0.35657700 0.00000000 C 1.51969700 -0.78799000 -0.49060700 H 1.20468100 1.90135600 0.00000000 H 2.42969800 -1.18718400 -0.00717900 C 0.22467300 0.25370200 -1.13535600 H 1.47271500 -1.20957700 -1.51011200 H 0.51738600 0.48319100 -2.17263100 C 1.51969700 0.78799000 -0.49060700 C 0.22467300 0.25370200 1.13535600 H 2.42969800 1.18718400 -0.00717900 H 0.51738600 0.48319100 2.17263100 H 1.47271500 1.20957700 -1.51011200 C 0.22467300 -1.28269400 -0.78364700 H 0.23333600 -2.16908100 0.74266100 H -0.64983800 -1.79989000 -1.21229400 H 0.23333600 2.16908100 0.74266100 H 1.13376100 -1.76710600 -1.18327800 C -0.94726400 0.76901100 -0.55690700 C 0.22467300 -1.28269400 0.78364700 C -0.94726400 -0.76901100 -0.55690700 H 1.13376100 -1.76710600 1.18327800 H -1.08800400 -1.33092500 -1.48800600 H -0.64983800 -1.79989000 1.21229400 H -1.08800400 1.33092500 -1.48800600 H -2.33569500 0.00000000 1.09251600 HF = -272.72519980 H -3.03599700 0.00000000 -0.60390200 Sum of electronic and zero-point Energies = -272.574149 Sum of electronic and thermal Energies = -272.569023 HF = -312.04153781 Sum of electronic and thermal Enthalpies = -272.568079 Sum of electronic and zero-point Energies = -311.861152 Sum of electronic and thermal Free Energies = -272.602595 Sum of electronic and thermal Energies = -311.855406 Sum of electronic and thermal Enthalpies = -311.854462 Sum of electronic and thermal Free Energies = -311.890488
(A) (B)
P -1.68276800 -0.37098900 0.05301800 P 1.78965900 0.29751100 0.04423200 C -3.11159300 0.38375300 -0.86403600 C 3.06985200 0.15806100 -1.30791000 C -4.44432400 -0.13065200 -0.83074200 C 4.41844500 0.63083300 -1.23978300 C -2.81084400 1.51599200 -1.65950200 C 2.59773800 -0.42376700 -2.51310300 C -5.42390500 0.54248200 -1.60040000 C 5.23203100 0.46913500 -2.38692400 C -3.80163600 2.16612300 -2.41407000 C 3.42387100 -0.56650800 -3.64068600 H -1.77355200 1.87757600 -1.70131700 H 1.55371800 -0.76248700 -2.56973900 C -5.12006100 1.67297100 -2.38211500 C 4.75575900 -0.11831200 -3.57368300 H -6.45312300 0.16228500 -1.58248000 H 6.26996800 0.82247100 -2.34235300 H -3.54608900 3.04044600 -3.02355200 H 3.02978200 -1.02131600 -4.55670700 H -5.90929300 2.16262100 -2.96457600 H 5.42141100 -0.22165400 -4.43857700 C -1.95846600 -0.02961900 1.86098400 C 2.40954900 -0.60602600 1.53290800 Annexes | 159
C -0.95982600 -0.34828000 2.83500200 C 1.69108000 -0.55522700 2.76597200 C -3.13574800 0.65372200 2.25438000 C 3.53224500 -1.45888300 1.39899700 C -1.22242400 -0.01616200 4.18383800 C 2.17189300 -1.33531000 3.84317200 C -3.36498700 0.98402200 3.60195100 C 3.98202700 -2.23432600 2.48317800 H -3.87781500 0.94031400 1.50119400 H 4.06003300 -1.51953500 0.43965200 C -2.40804800 0.63559800 4.57424100 C 3.30499000 -2.16193500 3.71626100 H -0.47036300 -0.26850600 4.94211800 H 1.63522400 -1.29695900 4.79981100 H -4.28569700 1.50645600 3.88556300 H 4.85546900 -2.88533300 2.36320900 H -2.57608000 0.88011200 5.62964300 H 3.64885900 -2.75449000 4.57208500 C 0.36885200 -0.98140500 2.48051100 C 0.43934300 0.27769200 2.95863000 H 0.99289000 -1.11395500 3.37891600 H -0.13578900 -0.07992600 3.82836800 H 0.26372000 -1.96345800 1.98882400 H 0.68006100 1.34235200 3.12758700 H 0.93129800 -0.34211800 1.76832900 H -0.21912900 0.23543300 2.07006800 C -4.86745000 -1.35683900 -0.04419500 C 5.02401700 1.32139700 -0.03552400 H -4.56652400 -2.28464600 -0.56294500 H 4.67752400 2.36861300 0.02731900 H -4.41870700 -1.39229700 0.96184100 H 4.75902000 0.82747700 0.91323700 H -5.96327000 -1.37859000 0.07107200 H 6.12299600 1.33912000 -0.11366500 Pd 0.29665200 0.90277600 -0.36690100 Pd -0.36148100 -0.30152100 -0.94516700 C 1.24799400 -0.63116200 -1.38036800 C -2.19460100 -0.26066200 -2.04233300 C -1.76612100 -2.20054200 -0.23108100 C 1.67813100 2.10219800 0.48514700 C -1.72626600 -2.72847700 -1.55695300 C 0.76414800 2.90303500 -0.24896100 C -1.86231100 -3.07236700 0.88008700 C 2.45690900 2.67991800 1.51120800 C -1.75788200 -4.13575500 -1.70597800 C 0.68474800 4.28319700 0.03152200 C -1.90253000 -4.46562500 0.70213600 C 2.35650200 4.05630400 1.79336500 H -1.94232900 -2.66038600 1.89267800 H 3.13104600 2.05439100 2.10755600 C -1.84000900 -5.00091100 -0.59988700 C 1.47937600 4.86214300 1.04174400 H -1.72467600 -4.55551700 -2.71951800 H -0.01599900 4.90812200 -0.53588100 H -1.98471600 -5.12475600 1.57387600 H 2.95965700 4.49275900 2.59779500 H -1.86359400 -6.08600500 -0.75423300 H 1.39922900 5.93501600 1.25141700 C -1.72531200 -1.86790900 -2.80660900 C -0.15085600 2.28703800 -1.28609100 H -1.29203500 -2.41961800 -3.65716200 H -0.84291600 3.01333700 -1.74501400 H -2.75686600 -1.58305200 -3.08406300 H 0.40197600 1.80046600 -2.11302600 H -1.15987400 -0.92980000 -2.68220200 H -0.88377300 1.59778000 -0.75622500 B 2.67968200 -0.88808100 -0.77322300 B -3.29325300 0.23744000 -1.03853100 O 3.81011500 -0.18074900 -1.14816200 O -3.32046700 1.52423000 -0.51595000 O 2.93135600 -1.91094900 0.11936200 O -4.34920000 -0.55070600 -0.62092800 C 4.97649100 -0.96524800 -0.67593600 C -4.41827000 1.57074400 0.47511000 C 4.35609800 -1.81591000 0.50760600 C -5.32455100 0.34892100 0.03371300 C 6.08787800 0.00680200 -0.26743600 C -5.09420600 2.94300500 0.38772400 H 6.96013900 -0.54559600 0.12332800 H -5.96205300 2.99159700 1.06842100 H 6.41983200 0.58220100 -1.14806600 H -4.38289700 3.73021000 0.69102500 H 5.75452800 0.71888500 0.50429700 H -5.43780100 3.16513600 -0.63433400 C 5.42815100 -1.82012900 -1.87370600 C -3.76849400 1.38292000 1.85800100 H 5.66132900 -1.15679500 -2.72338700 H -3.00798100 2.16781600 2.01060200 H 6.33246800 -2.40458600 -1.63403800 H -4.51342500 1.46463800 2.66746700 H 4.63563800 -2.51894500 -2.19277700 H -3.27397800 0.39901800 1.94037900 C 4.91531400 -3.23577900 0.64609300 C -5.99606100 -0.41024500 1.18273500 H 5.99388100 -3.20734500 0.88023000 H -6.69524400 0.24880100 1.72658100 H 4.40277400 -3.75849500 1.47129600 H -6.57568300 -1.25689800 0.77796400 H 4.77055600 -3.82409200 -0.27304500 H -5.26091200 -0.80908200 1.89948300 C 4.39201400 -1.09533300 1.86747200 C -6.36135000 0.71574200 -1.04381600 H 3.78395600 -1.66265500 2.59196600 H -6.81100000 -0.20980800 -1.44049600 H 5.42067600 -1.02842200 2.26013700 H -7.16981300 1.34272800 -0.63118800 H 3.97945800 -0.07321400 1.79875900 H -5.89488000 1.25592100 -1.88581800 C 1.57300600 3.32667100 0.98470200 C -1.98936400 -3.08988500 -0.61239700 C 0.61260800 3.84932900 -1.02360400 C -0.25491800 -2.96390100 0.86904400 C 0.14616800 3.60583500 0.43927200 C -1.75668900 -2.58965400 0.83518800 H -0.34817700 4.47752900 0.90183200 H -2.35371200 -3.14470100 1.57836100 H -0.56106400 2.74214200 0.55869500 H -1.93892900 -1.50622700 0.94561300 160 | Appendix A
C 2.30341600 4.65661300 0.57222400 C -1.52860100 -4.58736700 -0.47615100 H 2.10936500 5.43637000 1.32837600 H -2.36013300 -5.18855700 -0.07145900 H 3.39526900 4.52186000 0.50401600 H -1.24144600 -5.03059900 -1.44447500 C 1.64584500 5.01497200 -0.80268100 C -0.33492300 -4.50307400 0.53553600 H 1.11076500 5.97878200 -0.75628900 H -0.54764800 -5.06025500 1.46370200 H 2.37564100 5.07783600 -1.62631100 H 0.61047500 -4.89487200 0.12417100 H 1.66322400 3.05874800 2.04780400 H -2.99309300 -2.94720500 -1.03608400 H -0.16150600 4.05941000 -1.77679700 H 0.32474900 -2.72348700 1.77147600 C 1.46880600 2.60428200 -1.25612500 C 0.25298000 -2.36829900 -0.43738200 C 2.05885900 2.28395300 -0.02174200 C -0.83131100 -2.43548800 -1.36345200 H 0.60948300 -1.52507400 -1.32309200 H -1.86394900 0.50070500 -2.77539300 H 1.26845900 -0.22870500 -2.40932600 H -2.49837200 -1.16408500 -2.58527700 H 1.86064800 2.30136500 -2.23342300 H 1.30602800 -2.45969000 -0.72999900 H 2.97418000 1.69270900 0.08250900 H -0.68848300 -2.57530200 -2.44153900
HF = -2005.41271736 HF = -2005.39910017 Sum of electronic and zero-point Energies = -2004.697417 Sum of electronic and zero-point Energies = -2004.683696 Sum of electronic and thermal Energies = -2004.658916 Sum of electronic and thermal Energies = -2004.645512 Sum of electronic and thermal Enthalpies = -2004.657972 Sum of electronic and thermal Enthalpies = -2004.644568 Sum of electronic and thermal Free Energies = -2004.763373 Sum of electronic and thermal Free Energies = -2004.749311
(C) (D)
P 1.67421200 -0.24167400 0.00823600 P 1.05472800 -0.90288000 0.03948400 C 2.40965400 -0.16911100 1.71459700 C 1.16067800 -2.04388400 -1.42925500 C 3.78359600 -0.43480000 2.00907800 C 2.23799800 -2.95558000 -1.65846900 C 1.50486200 0.11214600 2.76784500 C 0.10739300 -1.94779900 -2.37114300 C 4.18721400 -0.37103200 3.36427600 C 2.18406100 -3.75025400 -2.82909400 C 1.93128000 0.16567400 4.10589900 C 0.07792800 -2.74769200 -3.52609400 H 0.44600900 0.27128300 2.52766400 H -0.68828200 -1.20685300 -2.20436200 C 3.28619900 -0.07293500 4.40388400 C 1.12640800 -3.65908100 -3.75360500 H 5.23980900 -0.56674400 3.60488200 H 3.00133300 -4.45828300 -3.01609900 H 1.21320100 0.38707400 4.90384800 H -0.74772300 -2.65303800 -4.24064500 H 3.64156200 -0.03400600 5.44030800 H 1.12637800 -4.29292400 -4.64814800 C 2.45145600 1.08691800 -1.02264000 C 0.80657800 -1.96862300 1.54675900 C 2.07674300 1.27652500 -2.39002000 C 0.61956000 -1.39492700 2.84577200 C 3.32897600 2.00542200 -0.39578500 C 0.68648000 -3.36976400 1.37071800 C 2.65440200 2.36284900 -3.08775200 C 0.38454600 -2.27506100 3.92702800 C 3.88000500 3.08383000 -1.11111800 C 0.43589800 -4.21942300 2.46279500 H 3.58125700 1.88164100 0.66371500 H 0.78500900 -3.80355500 0.36946000 C 3.55074200 3.25529400 -2.46937900 C 0.29757300 -3.66955300 3.75138100 H 2.38333900 2.51300800 -4.14066100 H 0.25704300 -1.84905700 4.93032300 H 4.56137100 3.78001400 -0.60894700 H 0.35558100 -5.30085400 2.30410100 H 3.97781600 4.08659800 -3.04246100 H 0.11217700 -4.31928900 4.61475100 C 1.08581500 0.38733100 -3.11467200 C 0.61111200 0.09727700 3.10404400 H 0.72524000 0.87384100 -4.03571800 H 0.50846500 0.30700800 4.18109300 H 1.52928200 -0.58443300 -3.39545200 H 1.51762200 0.60486600 2.73425800 H 0.20987700 0.16080900 -2.46942700 H -0.23712400 0.57430800 2.57402200 C 4.82089900 -0.81371600 0.97013400 C 3.44070400 -3.10667100 -0.74680200 H 4.69868100 -1.86675300 0.65894700 H 4.15352300 -2.27544300 -0.89264100 Annexes | 161
H 4.75562100 -0.19708100 0.05903700 H 3.16749300 -3.11308500 0.32079700 H 5.83681300 -0.70327800 1.38251100 H 3.97240600 -4.04648600 -0.96716100 Pd -0.60914200 -0.16313900 -0.01250300 Pd -1.01093000 0.11268900 -0.01238200 C -2.82789300 1.16654800 1.97985300 C -3.19522800 0.96287100 0.87102700 C 2.15880000 -1.89249400 -0.69830400 C 2.71016300 -0.07863700 0.15292800 C 1.60514300 -3.09475600 -0.16361600 C 3.19482900 0.70987700 -0.93144500 C 3.08439800 -1.95387700 -1.76757200 C 3.50758700 -0.27762000 1.30345600 C 2.00093300 -4.32247800 -0.74359900 C 4.47722000 1.29107600 -0.80081700 C 3.46535300 -3.18707300 -2.32453700 C 4.78103900 0.30895800 1.40695500 H 3.53321100 -1.03025500 -2.15189000 H 3.15058000 -0.92417600 2.11340500 C 2.91479200 -4.37879300 -1.81289500 C 5.26624800 1.10324500 0.34960600 H 1.58414400 -5.25398500 -0.33986200 H 4.86547700 1.89783800 -1.62901700 H 4.18869800 -3.21406300 -3.14755500 H 5.38863200 0.13909100 2.30315600 H 3.19876900 -5.34796900 -2.23937100 H 6.25762600 1.56685700 0.41532500 C 0.66337800 -3.12133000 1.02422000 C 2.42821800 0.90864800 -2.22233300 H 0.13168100 -4.08485400 1.08703800 H 2.82801500 1.76784800 -2.78563300 H 1.21262700 -2.97196000 1.97183800 H 2.50804500 0.01869300 -2.87264800 H -0.09603300 -2.30808600 0.98197900 H 1.35006000 1.07626600 -2.04779200 B -3.50999900 0.15627200 0.98736900 B -0.30706800 1.99897300 -0.10448700 O -2.76806400 -0.46768600 -0.03004900 O 0.79006800 2.52365900 0.52228800 O -4.79555300 -0.30425900 1.03935200 O -1.11756000 2.90602000 -0.75347100 C -3.70120000 -1.32400600 -0.84114900 C 0.60817700 4.00741100 0.49954100 C -4.89399500 -1.51246200 0.18701600 C -0.38912500 4.21363000 -0.71639600 C -2.95918000 -2.60320700 -1.23037800 C 1.98439500 4.65241400 0.32288300 H -3.63358300 -3.28041900 -1.78241300 H 1.88715000 5.74960800 0.24520700 H -2.11468000 -2.36010100 -1.89979000 H 2.61613200 4.42815000 1.19843000 H -2.57181400 -3.14236900 -0.35188200 H 2.49976300 4.28007300 -0.57568200 C -4.07727600 -0.51078900 -2.08700000 C 0.00553500 4.38305700 1.86315700 H -3.16371700 -0.24209800 -2.64470400 H 0.67787200 4.03243500 2.66384200 H -4.72166900 -1.10444900 -2.75688200 H -0.10803000 5.47568200 1.96411100 H -4.61392000 0.41668700 -1.82699700 H -0.98291000 3.91573200 2.01572700 C -6.28500500 -1.53857700 -0.45301300 C -1.42423900 5.32453400 -0.52338000 H -6.38448700 -2.39990500 -1.13635600 H -0.92466000 6.30558800 -0.43880300 H -7.04740600 -1.64235900 0.33660200 H -2.09642100 5.36303000 -1.39701800 H -6.49938700 -0.61539700 -1.01295600 H -2.03715200 5.16815200 0.37807300 C -4.70958500 -2.71658700 1.12753400 C 0.30826800 4.35867100 -2.07734000 H -5.47426500 -2.66933400 1.92008100 H -0.44676100 4.29914100 -2.87903600 H -4.83061500 -3.67195400 0.58949100 H 0.82179400 5.33165000 -2.16014700 H -3.71802400 -2.70858100 1.61340300 H 1.04874800 3.55872200 -2.24235700 C -2.62555700 3.33466700 0.54591700 C -5.32469600 -0.59587500 0.61313200 C -0.88373200 2.73166500 -0.78316600 C -3.51243300 -1.40333700 -0.50851300 C -2.42460500 2.81404000 -0.89902800 C -4.21858300 -1.65271000 0.84822700 H -2.75987200 3.53704800 -1.66312900 H -4.62749200 -2.67479800 0.91484700 H -2.89810500 1.84040500 -1.09871400 H -3.58865700 -1.48108600 1.73611500 C -1.75893500 4.62210800 0.52643300 C -5.93953500 -1.11024800 -0.72545400 H -2.31523800 5.45459700 0.06229600 H -6.66980200 -1.91391500 -0.53149500 H -1.46631500 4.94452900 1.54057500 H -6.46354900 -0.30955200 -1.27421200 C -0.53511200 4.20341900 -0.35663700 C -4.68818200 -1.65779700 -1.50644000 H -0.45243100 4.82833900 -1.26305300 H -4.78191500 -2.73750800 -1.71320000 H 0.42930900 4.26792700 0.17573000 H -4.53127800 -1.14746100 -2.47232000 H -3.66773400 3.49523900 0.87016000 H -6.05003600 -0.45231000 1.42974800 H -0.31725100 2.40469700 -1.66806800 H -2.61886100 -2.02230100 -0.71376600 C -0.67908000 1.87647500 0.47880300 C -3.30810200 0.13371400 -0.52691200 C -1.87939600 2.26354700 1.41225200 C -4.52921000 0.66556000 0.23176300 H -1.43187800 2.75484200 2.29910800 H -5.07252500 1.51781100 -0.19134300 H 0.30205100 2.04539400 0.95095300 H -3.04897100 0.64493400 -1.46392100 H -3.60471500 1.66208100 2.59017200 H -2.93887900 0.46291500 1.81137400 H -2.25546700 0.53547800 2.69339800 H -2.87434500 2.00432900 0.78241800
162 | Appendix A
HF = -2005.43800780 HF = -2005.39908722 Sum of electronic and zero-point Energies = -2004.719878 Sum of electronic and zero-point Energies = -2004.682162 Sum of electronic and thermal Energies = -2004.682197 Sum of electronic and thermal Energies = -2004.643841 Sum of electronic and thermal Enthalpies = -2004.681253 Sum of electronic and thermal Enthalpies = -2004.642897 Sum of electronic and thermal Free Energies = -2004.784392 Sum of electronic and thermal Free Energies = -2004.748175
(TSA-B) (TSB-C)
P -1.42275700 -0.61287100 0.05008500 P -1.29758600 -0.47737700 0.04189300 C -2.72970300 -0.69351200 -1.27081000 C -2.45589800 -0.61923500 -1.41417800 C -3.76558900 -1.67449900 -1.35389800 C -3.64321100 -1.41657700 -1.42661800 C -2.62570400 0.30123800 -2.27394400 C -2.06882700 0.07256300 -2.58823000 C -4.66091600 -1.59503300 -2.44775100 C -4.40472300 -1.44302900 -2.62023300 C -3.52758600 0.36159100 -3.35013600 C -2.83760500 0.02475700 -3.76334700 H -1.81138400 1.03558300 -2.20857300 H -1.12475700 0.63315500 -2.58491300 C -4.55456000 -0.59731600 -3.43545100 C -4.02188800 -0.73554300 -3.77499700 H -5.46303300 -2.34029500 -2.52116000 H -5.32251400 -2.04430700 -2.63931800 H -3.42615800 1.14211800 -4.11314200 H -2.51146100 0.56837800 -4.65750100 H -5.26903300 -0.57269500 -4.26665700 H -4.64111000 -0.78644500 -4.67824900 C -2.27672800 -0.12543300 1.62721800 C -2.25094400 0.36163100 1.40275700 C -1.52063200 0.12994500 2.81277200 C -1.63749600 0.66561400 2.65721900 C -3.67127300 0.11814700 1.61775800 C -3.56717300 0.81339400 1.14064700 C -2.21203800 0.57835700 3.96175400 C -2.40289600 1.35889000 3.62394200 C -4.33544900 0.57208600 2.77215400 C -4.30275000 1.51558400 2.11308800 H -4.24490600 -0.03483000 0.69673100 H -4.02312100 0.62356300 0.16269300 C -3.60356300 0.79338100 3.95441600 C -3.72309400 1.77569500 3.36940200 H -1.64049500 0.76727600 4.87950900 H -1.94245500 1.58405600 4.59441900 H -5.41688800 0.74834900 2.74422500 H -5.32154800 1.85089500 1.88764500 H -4.10915400 1.14154900 4.86272500 H -4.28750700 2.31203400 4.14117500 C -0.01805200 -0.04263800 2.87776900 C -0.20128800 0.31110600 2.97871000 H 0.38770700 0.37478500 3.81365400 H 0.14749200 0.85644000 3.87073100 H 0.27893400 -1.10482100 2.82008900 H -0.06963400 -0.76876700 3.16855200 H 0.48071200 0.46782400 2.02752700 H 0.46333500 0.56691600 2.13044000 C -3.94985300 -2.80002900 -0.35484900 C -4.12105100 -2.26405500 -0.26304000 H -3.19621400 -3.59307400 -0.50688300 H -3.54256700 -3.20315300 -0.19920800 H -3.84851000 -2.45836100 0.68826500 H -4.01763800 -1.75556600 0.70841000 H -4.94602700 -3.25742100 -0.46930200 H -5.18143900 -2.53387900 -0.39534400 Pd 0.46520800 0.99898800 -0.67975200 Pd 0.64085500 0.75553700 -0.63371100 C 2.11803900 1.13711300 -1.89590900 C 2.38505400 1.51200800 -1.74529100 C -0.80740200 -2.35199300 0.29563900 C -1.00582400 -2.23831500 0.57759700 C -0.07940500 -2.99155400 -0.74983100 C -0.40450800 -3.17028000 -0.32138900 C -1.03247500 -3.02795700 1.51719200 C -1.40473000 -2.65794500 1.86843200 C 0.40279000 -4.30117100 -0.52243700 C -0.21466000 -4.49733600 0.13200400 C -0.54266100 -4.33049900 1.72243900 C -1.20215100 -3.98242700 2.29615800 H -1.62099100 -2.54337900 2.30550700 H -1.91565400 -1.95439000 2.53552400 C 0.18126800 -4.97023000 0.69670100 C -0.59770200 -4.90767300 1.42334100 H 0.95798100 -4.80486600 -1.32403600 H 0.23453900 -5.22616500 -0.55498700 H -0.73356300 -4.84191500 2.67302700 H -1.52446200 -4.28738100 3.29839500 H 0.56596600 -5.98662300 0.84184200 H -0.43497000 -5.94457000 1.74002200 C 0.15076600 -2.34180900 -2.09660100 C -0.01378800 -2.82169000 -1.74328200 Annexes | 163
H 0.94936200 -2.85372000 -2.65684500 H 0.63600700 -3.60204100 -2.17232800 H -0.76714400 -2.34556500 -2.71180200 H -0.90525000 -2.73207000 -2.38952100 H 0.45493500 -1.28060000 -1.98369000 H 0.53296800 -1.86329600 -1.79764800 B 3.14941700 0.36414100 -0.99690900 B 3.13055700 0.44692800 -0.87624100 O 2.97239000 -0.96526000 -0.65493000 O 2.57012800 -0.83165200 -0.72511000 O 4.29259500 0.94108300 -0.49315200 O 4.31952500 0.62474400 -0.21892800 C 4.04700900 -1.29929700 0.31600200 C 3.43810900 -1.55305300 0.27139900 C 5.12362900 -0.17037500 0.03477900 C 4.78583800 -0.72234100 0.18514500 C 4.51621400 -2.72940900 0.03285300 C 3.55739400 -3.01188600 -0.17273900 H 5.35608800 -2.99815100 0.69713100 H 4.27269400 -3.54561400 0.47742000 H 3.68984600 -3.43411700 0.22612000 H 2.57973100 -3.51332200 -0.08037200 H 4.84162600 -2.85487900 -1.01125600 H 3.90295600 -3.09765200 -1.21437700 C 3.41399000 -1.21012800 1.71416700 C 2.74410500 -1.45271200 1.63394600 H 2.54536000 -1.88847200 1.75882100 H 1.73710200 -1.89649100 1.56626900 H 4.13137400 -1.51318300 2.49518300 H 3.31193900 -2.00543900 2.40125500 H 3.06988900 -0.18546600 1.93781200 H 2.64925500 -0.40382400 1.96219200 C 5.87285600 0.33158600 1.27269800 C 5.54182900 -0.59064800 1.51099900 H 6.46180400 -0.48543600 1.72471000 H 5.86722200 -1.58100200 1.87422500 H 6.57234900 1.13282700 0.98138400 H 6.44229600 0.02697100 1.35759600 H 5.18779300 0.73383800 2.03531100 H 4.92838400 -0.11239300 2.29031000 C 6.11480700 -0.53106800 -1.08561500 C 5.73237900 -1.20106000 -0.92946800 H 6.69546600 0.36638900 -1.35643000 H 6.54386000 -0.46466700 -1.05077900 H 6.82103800 -1.31398700 -0.76141900 H 6.18524000 -2.17598300 -0.68286000 H 5.59280300 -0.88605900 -1.99112400 H 5.20909500 -1.29333000 -1.89696800 C 0.29643500 3.68570300 1.02370400 C 1.41390500 4.05686900 -0.50725400 C -1.21504100 3.69086300 -0.68966500 C -0.36388300 3.35948000 0.73897800 C -1.18231000 3.28125100 0.80443100 C 1.16325900 3.54734600 0.93252100 H -1.87706400 3.87629200 1.42050900 H 1.40842100 4.30063300 1.70008800 H -1.38488100 2.21361200 0.97697700 H 1.69966800 2.60755800 1.15378200 C 0.24010800 5.20463900 0.59865600 C 0.42588700 5.27811100 -0.57105200 H -0.11630800 5.79912500 1.45696500 H 0.92159300 6.16440500 -0.14057100 H 1.22695300 5.60132300 0.30686500 H 0.13909300 5.53258400 -1.60551700 C -0.79434700 5.20860700 -0.57702800 C -0.78358400 4.80841700 0.30466800 H -1.68766000 5.80813600 -0.33333800 H -0.90130200 5.43924700 1.20210800 H -0.37583300 5.60433000 -1.51760000 H -1.74307700 4.82394600 -0.23906600 H 0.74061200 3.50538700 2.01341600 H 2.44887100 4.30170000 -0.79044800 H -2.14340200 3.51372300 -1.25211200 H -0.94395300 2.95479400 1.57984800 C 0.05304400 3.05146400 -1.24151000 C -0.43188900 2.55828100 -0.56467200 C 1.00518400 3.05384100 -0.16730600 C 0.71655200 2.98922300 -1.34697100 H 1.71811600 0.59326400 -2.77227700 H 2.08542100 1.17942000 -2.75309600 H 2.42566100 2.15476600 -2.18287700 H 2.92509800 2.46339200 -1.79694400 H 0.32854500 3.15003400 -2.29933100 H -1.40919900 2.39940800 -1.04008700 H 2.08747400 3.16455900 -0.30010300 H 0.64930600 3.08984800 -2.43632000
HF = -2005.39337061 HF = -2005.40490550 Sum of electronic and zero-point Energies = -2004.676042 Sum of electronic and zero-point Energies = -2004.686243 Sum of electronic and thermal Energies = -2004.638462 Sum of electronic and thermal Energies = -2004.648865 Sum of electronic and thermal Enthalpies = -2004.637518 Sum of electronic and thermal Enthalpies = -2004.647921 Sum of electronic and thermal Free Energies = -2004.740943 Sum of electronic and thermal Free Energies = -2004.750088 Frequency = -73.4866 Frequency = -136.6018
164 | Appendix A
(TSA-C) (TSC-D)
P -1.77662200 0.16160900 0.09996100 P 1.52163500 -0.23876200 0.08279900 C -2.96220000 -0.25051000 1.46255300 C 2.55134500 -1.22511400 -1.12082600 C -4.36411500 -0.47853800 1.30885000 C 3.97770800 -1.30675400 -1.09553500 C -2.37920500 -0.28423500 2.75352400 C 1.83272400 -1.91841100 -2.12570000 C -5.11903900 -0.73928700 2.47669200 C 4.60904800 -2.09725500 -2.08623000 C -3.15084100 -0.54220900 3.90022400 C 2.47888000 -2.70207700 -3.09604700 H -1.30304800 -0.09954900 2.86013600 H 0.73610400 -1.81881500 -2.17273300 C -4.53270400 -0.76983700 3.75696300 C 3.88352600 -2.79014600 -3.07364200 H -6.19614500 -0.92225000 2.37438200 H 5.70403000 -2.16794600 -2.07643000 H -2.67909700 -0.56234600 4.88919600 H 1.89546500 -3.22654800 -3.86131500 H -5.15446400 -0.97200300 4.63707700 H 4.41351400 -3.39143600 -3.82151300 C -1.58177800 -1.36310400 -0.94840800 C 1.68802400 -1.11059500 1.72186900 C -0.67359200 -1.36171100 -2.07987100 C 1.00082700 -0.65406200 2.88921200 C -2.17512100 -2.60228800 -0.52987400 C 2.42339000 -2.32085400 1.76912300 C -0.46255400 -2.60300100 -2.75760800 C 1.13400200 -1.41135900 4.07612100 C -1.94203700 -3.79017600 -1.22496300 C 2.52445200 -3.06461800 2.95830000 H -2.83669600 -2.59941800 0.34414400 H 2.92197700 -2.69242400 0.86737000 C -1.08270800 -3.78865800 -2.35476400 C 1.88408700 -2.60146000 4.12307200 H 0.18627300 -2.60180100 -3.64310400 H 0.62592400 -1.05701200 4.98204600 H -2.42943200 -4.71669000 -0.90058900 H 3.10571400 -3.99370600 2.97091200 H -0.90927600 -4.71497300 -2.91479900 H 1.96231500 -3.16384700 5.06088100 C -0.11863100 -0.10470400 -2.73554400 C 0.10771600 0.56840700 2.90675700 H 0.87246700 -0.31073500 -3.17311300 H -0.13063000 0.86110000 3.94254400 H -0.78376600 0.21953400 -3.55771700 H 0.56848900 1.43692500 2.40648600 H -0.02206200 0.74502300 -2.04140100 H -0.84803400 0.37047300 2.38823200 C -5.07399500 -0.45291200 -0.02875900 C 4.85235500 -0.58993700 -0.08626100 H -5.15256000 0.57695300 -0.41924200 H 4.91676800 0.48907800 -0.31241500 H -4.54215300 -1.04712700 -0.79202100 H 4.46710700 -0.68235700 0.94241600 H -6.09443200 -0.85806600 0.06533400 H 5.87503600 -0.99982500 -0.10515700 Pd 0.38592800 -1.03564300 0.15111000 Pd -0.74428400 -0.65646200 -0.63219800 C 1.77396300 -0.21721300 1.74634600 C -2.48817900 -1.01573200 -1.92266700 C -2.50765000 1.52357400 -0.91514400 C 2.34414400 1.42039000 0.19717200 C -2.44201400 2.85126900 -0.39916000 C 2.43498100 2.24645000 -0.96306800 C -3.09608000 1.27360500 -2.17660700 C 2.90936900 1.84462500 1.42233600 C -2.98733500 3.89274100 -1.18445000 C 3.09643700 3.49045400 -0.83204700 C -3.62381400 2.32781100 -2.94335800 C 3.55725400 3.08841100 1.52548500 H -3.15945500 0.24708400 -2.55754500 H 2.87567300 1.18468700 2.29723000 C -3.56973000 3.64411400 -2.44259900 C 3.64931900 3.91733300 0.39023100 H -2.95195700 4.91896000 -0.79742800 H 3.18398200 4.13239500 -1.71794000 H -4.08184000 2.12023600 -3.91736100 H 3.99424900 3.39840000 2.48158000 H -3.98202100 4.47439200 -3.02793200 H 4.15651900 4.88734200 0.45269100 C -1.82556900 3.16079900 0.95046700 C 1.89500900 1.83560700 -2.31680300 H -1.79119800 4.24842000 1.12558100 H 1.92367100 2.68352700 -3.02033400 H -2.41073600 2.70972100 1.77298100 H 2.49093700 1.01462300 -2.75395800 H -0.79392100 2.76734100 1.01501400 H 0.84769800 1.49204300 -2.24614400 B 2.37988100 1.04391700 1.00326900 B -1.49613100 1.19268400 -0.30286100 O 3.72382300 1.33969500 1.10808000 O -2.36010300 1.45518500 0.72941600 O 1.65145100 1.98818500 0.30287200 O -1.23487200 2.23478300 -1.15192200 Annexes | 165
C 3.90015200 2.73682600 0.65399700 C -2.90203400 2.82960900 0.47144500 C 2.61994900 2.96443200 -0.25414300 C -1.80494400 3.45225400 -0.48745400 C 5.24290300 2.84656200 -0.07536500 C -3.05957700 3.53447900 1.81999300 H 5.38989400 3.86777300 -0.46807300 H -3.40173400 4.57393700 1.67258300 H 6.06421000 2.63425600 0.62949400 H -3.81786500 3.01228900 2.42731300 H 5.31782300 2.13502400 -0.91261600 H -2.11614700 3.55436700 2.38669900 C 3.90964100 3.60010700 1.92782000 C -4.27054700 2.64227700 -0.20112700 H 4.71711600 3.25181900 2.59325200 H -4.92537200 2.04718200 0.45707600 H 4.08968400 4.66296900 1.69438500 H -4.76072800 3.61464300 -0.37769100 H 2.95584900 3.51896900 2.47755300 H -4.18324200 2.12388100 -1.17212500 C 2.00260200 4.36329600 -0.16040600 C -2.34720600 4.37190700 -1.58339200 H 2.71240200 5.12452600 -0.52831900 H -2.83401900 5.25747800 -1.13841100 H 1.09710700 4.41321900 -0.78897600 H -1.51588400 4.72603100 -2.21559300 H 1.72175000 4.61954600 0.87281500 H -3.07582900 3.85885800 -2.22972900 C 2.83620400 2.57840300 -1.72737500 C -0.64555300 4.12183700 0.26330400 H 1.86711800 2.60028600 -2.25409700 H 0.16528400 4.35177300 -0.44642800 H 3.51419200 3.28798500 -2.23084800 H -0.97045200 5.06418200 0.73617300 H 3.26301800 1.56517100 -1.82445100 H -0.23221800 3.46233300 1.04541600 C 3.74844400 -1.96698900 0.79396200 C -4.58418900 -2.30057400 -0.90510000 C 2.67175100 -2.85113100 -1.01228400 C -3.15203800 -2.07600100 0.86581000 C 3.60191700 -1.64939400 -0.71581200 C -4.39029800 -1.34029000 0.29515200 H 4.56295000 -1.70548400 -1.25442900 H -5.24335100 -1.36578200 0.99418900 H 3.13158100 -0.67092300 -0.91358500 H -4.18375700 -0.29265600 0.03225600 C 4.28430400 -3.43890100 0.73701700 C -4.72567100 -3.66700400 -0.17068600 H 5.37881700 -3.42036800 0.60245000 H -5.75927400 -3.80826100 0.18693600 H 4.07732900 -3.99849000 1.66507300 H -4.48390900 -4.52091900 -0.82654300 C 3.56371400 -4.04232800 -0.51570500 C -3.72330100 -3.52816600 1.03286900 H 4.28548300 -4.31556500 -1.30498900 H -4.23851900 -3.60032700 2.00622400 H 2.96973400 -4.94169100 -0.28121300 H -2.93346300 -4.29945000 1.02580200 H 4.35922000 -1.27495500 1.39221800 H -5.40326200 -2.06253600 -1.60245100 H 2.29551300 -2.96794900 -2.03944500 H -2.68665300 -1.65418400 1.76795800 C 1.60348500 -2.70419700 0.07240900 C -2.24467700 -2.20328600 -0.35929900 C 2.28326400 -2.10870300 1.23082800 C -3.17989300 -2.32366700 -1.54419300 H 0.80270500 -0.03352900 2.24227600 H -2.99833900 -3.14655400 -2.25173000 H 2.46667900 -0.47378300 2.55928400 H -1.36396300 -2.88037100 -0.32124600 H 0.88174000 -3.52494000 0.21804900 H -3.10747900 -0.11394800 -1.85022600 H 2.05916000 -2.52483500 2.22142200 H -1.86230800 -1.06317900 -2.82649400
HF = -2005.37310250 HF = -2005.37841431 Sum of electronic and zero-point Energies = -2004.656204 Sum of electronic and zero-point Energies = -2004.660844 Sum of electronic and thermal Energies = -2004.618270 Sum of electronic and thermal Energies = -2004.623083 Sum of electronic and thermal Enthalpies = -2004.617326 Sum of electronic and thermal Enthalpies = -2004.622138 Sum of electronic and thermal Free Energies = -2004.721313 Sum of electronic and thermal Free Energies = -2004.725986 Frequency = -337.5690 Frequency = -221.0049
(E) (F) P -1.14706400 0.13700100 -0.01909300 P -1.59831000 -0.27494400 0.04888500 C -2.47564600 -1.14084400 -0.24383200 C -2.72419600 0.32501300 -1.31012400 C -3.49906700 -1.49021800 0.68297500 C -4.14805800 0.19156400 -1.26531500 C -2.36017900 -1.84199300 -1.47681700 C -2.10407500 0.86141800 -2.46413100 166 | Appendix A
C -4.34959900 -2.56871600 0.33342200 C -4.88139300 0.65418400 -2.38560100 C -3.21520700 -2.90837900 -1.79903500 C -2.85515400 1.30190600 -3.56606300 H -1.64265100 -1.49693900 -2.25052800 H -1.00884400 0.90362700 -2.50643100 C -4.21133600 -3.27925900 -0.87387000 C -4.25883000 1.20398100 -3.52121700 H -5.14940400 -2.84842800 1.03060000 H -5.97513700 0.56890800 -2.36067600 H -3.11386600 -3.42863800 -2.75777600 H -2.34915500 1.71013000 -4.44842200 H -4.89212800 -4.10784900 -1.10045300 H -4.86689600 1.54495700 -4.36725200 C -1.78431000 1.69024100 -0.78785900 C -1.92235400 0.75662800 1.56572300 C -0.93311400 2.78417200 -1.12947900 C -1.15705900 0.60628000 2.76508300 C -3.17640300 1.75446100 -1.04854700 C -2.88911400 1.78760300 1.47231300 C -1.53391000 3.92591500 -1.70661400 C -1.45182100 1.46778500 3.84761700 C -3.74536700 2.90445900 -1.62298900 C -3.15128800 2.63944100 2.56008700 H -3.82130500 0.90241200 -0.80731000 H -3.44283000 1.93477200 0.53845300 C -2.91857000 3.99611600 -1.95151100 C -2.43755700 2.46915400 3.76147300 H -0.89454400 4.77667500 -1.97319700 H -0.88199700 1.35086200 4.77801200 H -4.82416000 2.94315200 -1.81121200 H -3.91064600 3.42401800 2.46598700 H -3.34858100 4.89820100 -2.40214100 H -2.63669100 3.11763700 4.62261700 C 0.56622100 2.75669600 -0.93582300 C -0.02239700 -0.38429200 2.91733400 H 0.99787100 3.75903800 -1.08787400 H 0.42770900 -0.31403000 3.92047000 H 0.86495700 2.39948700 0.06420900 H -0.34222300 -1.42881300 2.76038500 H 1.03344900 2.07337900 -1.67168200 H 0.76905900 -0.18184900 2.16857200 C -3.74230000 -0.76146200 1.99020600 C -4.92560600 -0.44294500 -0.12720900 H -3.00669000 -1.04809600 2.76262400 H -4.90374600 -1.54478900 -0.20688100 H -3.67516300 0.33321300 1.87522000 H -4.52864900 -0.18485800 0.86690700 H -4.74444500 -1.00226700 2.37961800 H -5.98096300 -0.12730600 -0.16438200 Pd 0.35533300 -1.05900900 -1.22845400 Pd 0.61549200 0.15294100 -0.48573500 C -0.75093100 0.45118700 1.74650200 C 0.98057400 -1.87191000 -0.25414800 C -0.23447000 -0.58125000 2.58881800 C -2.17403300 -2.00677100 0.40018500 C -0.94306000 1.76278000 2.24605000 C -2.23417000 -2.98773900 -0.63561300 C 0.06580800 -0.24030500 3.92696200 C -2.58301900 -2.33753300 1.71492300 C -0.63846500 2.06923200 3.58314300 C -2.68076900 -4.28469600 -0.28729500 H -1.34935500 2.54373200 1.59335500 C -3.03119300 -3.63166200 2.03022600 C -0.13013800 1.06162100 4.42653500 H -2.59116300 -1.56859800 2.49510500 H 0.45960100 -1.01970000 4.59139300 C -3.07023800 -4.61576800 1.02321900 H -0.80034200 3.08510500 3.96080000 H -2.72665800 -5.04939600 -1.07325400 H 0.11169300 1.28707900 5.47182700 H -3.34962400 -3.86386900 3.05284300 C -0.02478900 -2.00528900 2.12456900 H -3.40965000 -5.63229600 1.25380000 H 0.52210000 -2.59005200 2.88136100 C -1.91583900 -2.71347500 -2.09335000 H -0.98355800 -2.51883000 1.92720400 H -1.57694200 -3.63508500 -2.59511600 H 0.54893100 -2.03774600 1.17422700 H -2.81758100 -2.35855900 -2.62568800 B 2.10851300 -0.31652100 -0.62256300 H -1.14392200 -1.93997300 -2.23287300 O 2.56004000 0.34657100 0.47667200 B 2.52863900 -1.66053800 -0.15148100 O 3.05224800 -0.82005100 -1.48841700 O 3.13659000 -0.71693200 -0.98272600 C 4.04747400 0.45701000 0.28279600 O 3.38809500 -2.29166600 0.71162500 C 4.35166300 -0.72902000 -0.72704500 C 4.61095500 -0.92298800 -0.83147100 C 4.70998800 0.31702900 1.65396300 C 4.71058800 -1.63868500 0.57945100 H 5.80931200 0.33092500 1.55180200 C 5.33120700 0.42250600 -0.92449300 H 4.41919300 1.16490500 2.29629200 H 6.41782900 0.27786400 -0.79400800 H 4.41659600 -0.61585800 2.15957800 H 5.17127500 0.86565500 -1.92247000 C 4.30315700 1.84961200 -0.31178700 H 4.98457100 1.13381600 -0.15919000 H 3.89198000 2.61506800 0.36729100 C 5.00917400 -1.82847300 -2.01013800 H 5.38385400 2.03922700 -0.42557300 H 4.73294000 -1.33557100 -2.95736200 H 3.82482600 1.96606600 -1.29930600 H 6.09693500 -2.01161700 -2.02077200 C 5.46372500 -0.45451800 -1.73899100 H 4.49230700 -2.80222200 -1.96580100 H 6.42600200 -0.30797400 -1.21717700 C 5.79176400 -2.72087600 0.67203800 H 5.57435300 -1.31812300 -2.41565900 H 6.79437800 -2.28445100 0.51905800 H 5.25532100 0.43783600 -2.34874700 H 5.76976600 -3.17809100 1.67535300 C 4.54689300 -2.09032000 -0.04424600 H 5.63729500 -3.51949200 -0.06966300 H 4.54179300 -2.88422500 -0.80962900 C 4.83038300 -0.66139800 1.76202300 Annexes | 167
H 5.51314800 -2.13284100 0.48637100 H 4.69545700 -1.22040200 2.70284900 H 3.74257600 -2.30181400 0.68156500 H 5.82179000 -0.17813700 1.78751400 H 4.05836300 0.12681100 1.71877900 HF = -1693.31881249 C 2.41212500 2.86786700 -0.75899400 Sum of electronic and zero-point Energies = -1692.784079 C 0.76006300 3.26947000 0.75904200 Sum of electronic and thermal Energies = -1692.752845 C 2.19292100 2.67824300 0.76511400 Sum of electronic and thermal Enthalpies = -1692.751901 H 2.89990800 3.26172100 1.37993900 Sum of electronic and thermal Free Energies = -1692.843052 H 2.21668500 1.61769500 1.08038000 C 2.18142900 4.42147600 -0.88561500 H 3.11135600 4.95359600 -0.62122300 H 1.90760400 4.71895900 -1.91134900 C 1.04732200 4.69839500 0.15700900 H 1.39258400 5.37284100 0.95907400 H 0.14707000 5.14843300 -0.29306700 H 3.35503000 2.50626700 -1.19088700 H 0.19988700 3.27015100 1.70548200 C 0.12334400 2.51471400 -0.40230700 C 1.13161800 2.25792100 -1.32844600 H 0.50845800 -2.38116700 0.59718400 H 0.64864100 -2.33778400 -1.19764400 H -0.94495800 2.57071000 -0.63392900 H 0.98089600 2.08122500 -2.40163500
HF = -2005.41223278 Sum of electronic and zero-point Energies = -2004.696927 Sum of electronic and thermal Energies = -2004.658429 Sum of electronic and thermal Enthalpies = -2004.657485 Sum of electronic and thermal Free Energies = -2004.762588
(G) (H)
P -1.34544100 0.03826300 -0.02353500 P 1.17460800 0.15682500 0.01345400 C -1.81876200 -1.26758300 -1.25493000 C 1.61487100 0.51600000 1.78544100 C -3.09829200 -1.89920900 -1.30993300 C 2.80893600 1.14917900 2.25089900 C -0.81039000 -1.62789000 -2.18198500 C 0.66704200 0.03465600 2.72470600 C -3.29953400 -2.87681900 -2.31416500 C 2.97783300 1.28888100 3.64919100 C -1.03710100 -2.59435400 -3.17560600 C 0.86087200 0.17841900 4.10942900 H 0.18218000 -1.15256300 -2.11276500 H -0.24160000 -0.46327100 2.35847100 C -2.29473500 -3.22548000 -3.23657600 C 2.02723600 0.81528300 4.57311800 H -4.27667000 -3.37269700 -2.37139500 H 3.88715800 1.77957900 4.01870600 H -0.24402800 -2.85429900 -3.88566900 H 0.11148800 -0.20111600 4.81350300 H -2.49471800 -3.98641800 -3.99994600 H 2.19971100 0.94202200 5.64830300 C -2.21172500 1.60123300 -0.53812300 C 1.04300500 1.74662500 -0.91498000 C -1.96075100 2.85860700 0.09776200 C 0.76863200 1.73964200 -2.31698800 C -3.08073400 1.53642700 -1.65673900 C 1.07209900 2.96942800 -0.20012700 C -2.64707500 3.99321700 -0.39124300 C 0.58029400 2.98503700 -2.95857900 C -3.73985400 2.68460100 -2.12938200 C 0.87145400 4.19434300 -0.86219700 H -3.23922200 0.58280800 -2.17140300 H 1.24571600 2.96496400 0.88258900 C -3.52944400 3.91881000 -1.48598400 C 0.63519000 4.20197000 -2.25094600 H -2.47306200 4.96065500 0.09624900 H 0.37839300 2.99574500 -4.03725700 H -4.41174800 2.61024500 -2.99183900 H 0.90297000 5.13239900 -0.29632500 168 | Appendix A
H -4.03993600 4.82241400 -1.83903000 H 0.48286700 5.14962500 -2.78064800 C -0.96551300 3.04556100 1.22489600 C 0.66474800 0.46318300 -3.12751700 H -1.06433800 4.04842100 1.67081300 H 0.18373800 0.65420800 -4.10049200 H -1.08516600 2.30072400 2.03002800 H 1.65796900 0.02002300 -3.32147600 H 0.06820400 2.94995700 0.83822200 H 0.06674700 -0.30533800 -2.59720600 C -4.23948000 -1.59074600 -0.35974900 C 3.91477600 1.64655400 1.34321000 H -4.06657900 -2.03959800 0.63453100 H 4.54278700 0.80449700 0.99995300 H -4.37624300 -0.50743800 -0.20445400 H 3.52812600 2.15805800 0.44671300 H -5.18525400 -1.99841000 -0.75144400 H 4.57001600 2.35102900 1.88048000 Pd 0.88820900 0.43905700 -0.27883900 Pd -0.64995500 -1.42580800 -0.15607100 C 1.52170500 0.27259600 1.67674500 C -2.21510000 -2.83015200 -0.40208500 C -1.94927600 -0.48867400 1.64294000 C 2.57709700 -0.84939800 -0.68182600 C -1.50267700 -1.71682300 2.21826600 C 2.47727600 -2.25873500 -0.52615500 C -2.85483300 0.34401300 2.34280600 C 3.68630500 -0.29358000 -1.35133800 C -1.97812800 -2.04584200 3.50961000 C 3.51335800 -3.08097500 -1.01461300 C -3.31800200 -0.01363600 3.62094400 C 4.70922800 -1.12579300 -1.85088400 H -3.22494100 1.26429500 1.87600400 H 3.74386100 0.78978000 -1.50964500 C -2.86961500 -1.21210000 4.21060700 C 4.62956500 -2.51959100 -1.66923600 H -1.64280100 -2.98486800 3.96805800 H 3.44443700 -4.16974900 -0.89582800 H -4.02353200 0.63857500 4.14798700 H 5.55918600 -0.68456900 -2.38405500 H -3.21753900 -1.50093800 5.20922600 H 5.42211900 -3.17288300 -2.05152000 C -0.60422300 -2.70291800 1.49681100 C 1.26492900 -2.89399500 0.13079600 H -0.11014400 -3.37821000 2.21455000 H 1.32354700 -3.99638400 0.16651900 H -1.19039700 -3.32873900 0.79901300 H 1.08548600 -2.56130700 1.17033500 H 0.17595600 -2.20541000 0.89297900 H 0.34694000 -2.82787300 -0.59885300 B 2.95254200 0.14127600 1.06048800 B -3.15729400 -1.62061000 -0.17391300 O 3.11225400 0.89235100 -0.13629900 O -2.54133000 -0.39745400 -0.59382700 O 4.01538000 -0.65244700 1.35965200 O -4.35243600 -1.43137200 0.44633400 C 4.32772400 0.31933000 -0.81964500 C -3.34591100 0.72101800 0.03995600 C 5.11035600 -0.29126200 0.41554400 C -4.73881800 -0.00937100 0.23670900 C 5.03956000 1.46421000 -1.54060300 C -3.35034700 1.89229400 -0.94153200 H 5.98497400 1.10356300 -1.98211600 H -4.00980000 2.69393100 -0.56498000 H 4.40846400 1.84622900 -2.36090500 H -2.33335300 2.30780800 -1.04000200 H 5.26743600 2.29881500 -0.86054100 H -3.70383700 1.59046700 -1.93909100 C 3.81994700 -0.73436200 -1.81386300 C -2.66128000 1.09748400 1.35653900 H 3.13533900 -0.25586000 -2.53701900 H -1.62711600 1.42401200 1.15692500 H 4.65539900 -1.17062700 -2.38640200 H -3.19096800 1.93507600 1.84021900 H 3.28456300 -1.55441200 -1.30391100 H -2.64149700 0.25040100 2.06396600 C 5.90009100 -1.56459200 0.09930500 C -5.52205000 0.45420000 1.46866000 H 6.68881100 -1.35538400 -0.64415900 H -5.77792900 1.52481700 1.38488800 H 6.38807800 -1.93018600 1.01772700 H -6.46321500 -0.11581500 1.53647900 H 5.25300300 -2.36769600 -0.28634400 H -4.95938400 0.29449100 2.40132400 C 5.99330800 0.73152500 1.14951500 C -5.62969000 0.01785900 -1.01674100 H 6.34218400 0.28829500 2.09661500 H -6.48048100 -0.66619000 -0.86420500 H 6.87849500 0.99998800 0.54888600 H -6.02998300 1.02884500 -1.20162300 H 5.43913600 1.65562300 1.38872500 H -5.08406900 -0.31320900 -1.91733200 H 1.09309500 -0.56916700 2.23700700 H -2.09771000 -3.17523700 -1.44419100 H 1.24593600 1.23911400 2.12973200 H -2.23620400 -3.67314100 0.30485200
HF = -1732.64452453 HF= -1732.61946930 Sum of electronic and zero-point Energies = -1732.082353 Sum of electronic and zero-point Energies = -1732.058596 Sum of electronic and thermal Energies = -1732.050236 Sum of electronic and thermal Energies = -1732.026722 Sum of electronic and thermal Enthalpies = -1732.049292 Sum of electronic and thermal Enthalpies = -1732.025778 Sum of electronic and thermal Free Energies = -1732.141387 Sum of electronic and thermal Free Energies = -1732.117341
“Always being in a hurry does not prevent death, neither does going slowly prevent living.” ― Igbo Proverb
Appendix B
List of Publications and Presentations
Doctoral Publication
A. A. S. W. Tchawou, M. Raducan, P. Chen Mechanism-based Design and Optimization of a Catalytic Electrophilic Cyclopropanation without Diazomethane Organometallics 2016. In Press.
Pre-Doctoral Publication
D. Marković, A. S. W. Tchawou, I. Novosjolova, S. Laclef, D. Stepanovs, M. Turks, P. Vogel Synthesis and Applications of Silyl 2-Methylprop-2-ene-1-sulfinates in Preparative Silylation and GC-Derivatization Reactions of Polyols and Carbohydrates Chem. –Eur. J. 2016, 22, 4196–4205.
Presentations
XIVth Swiss Snow Symposium (SSS), Saas-Fee, Switzerland, 2016 Talk: “Mechanism-based design and optimization of a catalytic electrophilic cyclopropanation without diazomethane” A. A. S. W. Tchawou, M. Raducan, P. Chen Poster: “Mechanism-based design and optimization of a catalytic electrophilic cyclopropanation without diazomethane” A. A. S. W. Tchawou, M. Raducan, P. Chen
XXVth International Conference Organometallic Chemistry (ICOMC), Lisbon, 2012 Poster: “Enhancement of the coordination-insertion polymerization of methyl acrylate using palladium-based phosphino-sulfonate catalysts” A. A. S. W. Tchawou, P. Chen
International Symposium on Reactive Intermediates and Unusual Molecules (ISRIUM), Ascona, Switzerland, 2012 Poster: “Coordination–insertion polymerization of polar olefins using palladium(II) phosphine sulfonate catalysts: experimental evidence for a reversible Pd(II)–Pd(0) equilibrium after β-H elimination” A. A. S. W. Tchawou, P. Chen
Appendix C
Curriculum Vitae
First names Augustin Armand Senghor
Family names Tchawou Wandji
Date of birth November 23th, 1984
Place of birth Yagoua, Far-North Province, Cameroon
Nationality Cameroon
Education
2010 – 2016 Ph.D. in Chemistry under the supervision of Prof. Dr. Peter Chen at ETH Zürich, Switzerland
2008 – 2010 M.Sc. of Science in Biological and Molecular Chemistry, ETH Lausanne, Switzerland
2005 – 2008 B.Sc. of Science in Biological and Molecular Chemistry, ETH Lausanne, Switzerland
2004 – 2005 Special Mathematic Courses, ETH Lausanne, Switzerland
2002 – 2004 Diplôme d’Etudes Universitaires Générales en Chimie, Université de Yaoundé 1, Cameroun