I. Progress Toward the Development of an Alkyl Heck Reaction II

Home , Heck reaction, Palladacycle

I. Progress Toward the Development of an Alkyl Heck Reaction II. Preparation of an Unusual Palladacycle

Thesis

Presented in Partial Fulfillment of the Requirements for

the Degree Master of Science in the Graduate

School of The Ohio State University

Jimmy Alvarez

Graduate Program in Chemistry

The Ohio State University

2010

Thesis Committee:

Professor James P. Stambuli

Professor Jovica Badjic

Jimmy Malery Alvarez

2010

Abstract

Transition-metals have been an area of high interest in organic chemistry because of the myriad of chemical transformations they can achieve. The Heck reaction is an example of these tranformations and widely used in organic synthesis. But, it is limited because one can only use either aryl or alkenyl halides. The first topic that will be discussed in this thesis is the progress made toward developing an alkyl Heck reaction. The final goal was not achieved but a reductive alkylation on non-activated alkenes was accomplished.

The second topic deals with an interesting new palladacycle. Palladacycles have many applications in organic and bio-organic chemistry. A few of their applications are as catalyst, precatalyst, chiral auxiliaries and as mesogenic and photoluminescent agents. Palladacycle A was tested to see if it was the catalytically active Pd species in reactions catalyzed by Pd(OAc)2 and

P(t-Bu)3. It was found that palladacycle A was not the active catalyst but has potential as a precatalyst. The optimal conditions to afford palladacycle A were also established.

Dedication

To my family.

iii

Acknowledgments

I would like to begin by thanking Professor James P. Stambuli, my advisor, for allowing me to work in his group during my graduate career at The Ohio State University. He has been a very good mentor; his up-front demeanor has helped me to mature as a chemist and a person. His vast knowledge in both inorganic and organic chemistry was always inspirational. James’ advice and guidance supported me through my project from the very beginning. His drive and ambition rub off on his students and helps us become better chemist. The research going on in the Stambuli lab is amazing and will only get better. I also would like to thank Professor Jovica Badjic for serving on my thesis committee.

I would also like to thank the entire Stambuli group who. First, Dr. Nicolas Proust, thank you for answering so many questions and proofreading this thesis. A very special shout-out goes to William Henderson (Big 6), Sean Whittemore (Chankla), Chris Check (Baby Check) and Matt

Lauer (Stambuli Rules), for all the unforgettable weekends at Baby Check’s and Big 6’s. It wouldn’t have been the same without you guys. Brenda and Kamala you can finally take the earmuffs off. Thanks for all the birthday cakes Brenda, the banana cheese cake is still the best. I would also like to mention the rest of our group members who were always willing to lend a helping hand: Chad, Matt V., Mathieu and Carla. Last but not least our undergrads Eric, Jen, and

Zack.

My final thanks go to my parent, little brother, and my best friends Tasha, Ronald and

Antwyne, (I’m finally coming home) for everything they have done for me and always being behind me when I needed them. None of this would have been possible without you.

Vita

September 8th 1985 …...... Born – Los Angeles, California, USA

May 2007...... B. S. Chemistry, Edinboro University of Pennsylvania, Edinboro, Pennsylvania

August 2007- Present……………………………………..Graduate Teaching Assistant `The Ohio State University

Publications

Henderson, W.; Eichman, C.; Alvarez, J.; Gallucci, J.; Stambuli, J. “An Unusual Palladium(II) Complex from Palladium Acetate and Tri-tert-butyl Phosphine.” Organometallics, 2010, Manuscript in Preparation.

Field of Study

Major Field: Organic Chemistry

Table of Contents

Abstract ...... ii Dedication ...... iii Acknowledgments...... iv Vita...... vi List of Figures ...... ix List of Tables ...... x List of Schemes ...... xi List of Abbreviations ...... xiii Chapter 1 ...... 1 1.1 Background ...... 1 1.2 The Heck Reaction ...... 3 1.3 Palladacycle ...... 6 Chapter 2 ...... 10 2.1 Background Information ...... 10 2.2 Synthesis of the Heck Product ...... 11 2.3 Results and Discussion ...... 15 2.4 Ethereal Coordinating Alkenes ...... 15 2.5 Pyridyl Coordinating Alkenes ...... 19 2.6 Mechanistic Considerations ...... 22 2.7 Solvent Selection ...... 25 2.8 Base Selection ...... 26 2.9 Phosphine Selection ...... 28 2.10 Further Optimization ...... 29 2.11 Conclusion ...... 32 Chapter 3 ...... 33 3.1 Background ...... 33

vii

3.2 Results and Discussion ...... 34 3.3 Synthesis of Palladacycle A ...... 34 3.4 Variable Temperature NMR Experiments ...... 37 3.5 Amination Reactions ...... 40 3.7 Conclusion ...... 45 Chapter 4 ...... 46 4.1 General Methods ...... 46 4.2 Chapter 2: Experimental Methods ...... 47 4.3 Chapter 3: Experimental Methods ...... 54 Appendix ...... 56 Crystal Data ...... 65 Bibliography ...... 93

viii

List of Figures

1.1 Palladacycle A ...... 7

1.2 Types of Palladacycles ...... 8

1.3 Palladacycle B ...... 8

2.1 Ether J ...... 18

2.2 Pyridyl Alkenes K, L, M, N ...... 19

2.3 Proposed TS‡ ...... 22

3.1 A & B Mixture Goes to B ...... 35

3.2 2-4 Equivalents of P(t-Bu)3 with Pd(OAc)2 ...... 36

3.3 Variable Temperature 31P NMR ...... 38

3.4 Variable Temperature 1H NMR ...... 39

3.5 Amination Time Trial ...... 43

List of Tables

2.1 Hydrosilation Results ...... 14

2.2 Thioether Results ...... 16

2.3 De-allylation of Thioether E ...... 17

2.4 Vinyl-pyridine Results ...... 20

2.5 Results for Alkene K ...... 21

2.6 Solvent Screening ...... 25

2.7 Base Screening ...... 27

2.8 Further Base Optimization ...... 28

2.9 Ligand Screening ...... 29

2.10 Suppression of Double Bond Isomerization ...... 30

2.11 A Few Different Metal Sources ...... 31

2.12 Results with Alkene M ...... 32

3.1 Amination Results ...... 42

3.2 Hartwig’s Amination of Ortho-Substituted Aryl Haildes ...... 44

3.3 Amination of Ortho-Substituted Aryl Haldies ...... 44

List of Schemes

1.1 Cross-Coupling Reactions ...... 2

1.2 General Catalytic Cycle ...... 3

1.3 Heck Mechanism ...... 4

1.4 Fu’s “Alkyl Heck” ...... 5

1.5 Complex Induced Proximity Effect (CIPE) ...... 5

1.6 Yoshida’s CIPE “Proof of Principle” ...... 6

1.7 First Cyclometallated Complex ...... 7

1.8 Monoarylation of Nitriles ...... 9

2.1 CIPE ...... 10

2.2 First Proposed Route to Product ...... 11

2.3 Second Proposed Route to Product ...... 12

2.4 Final Proposed Route to Product ...... 12

2.5 Heck Products ...... 14

2.6 De-allylation of Thioethers ...... 18

2.7 Reductive Alkylation ...... 22

2.8 Proposed Mechanism ...... 24

3.1 Amination Reaction ...... 40

3.2 Amination Mechanism ...... 41

xii

List of Abbreviations

oC degree Celsius

1H nuclear magnetic resonance of proton

31P nuclear magnetic resonance of phosphorous avg average

β beta br broad (NMR)

Bu butyl calcd calculated cat catalytic

CDS chlorodimethylsilane

CDVS chloro(dimethyl)vinylsilane

CIPE complex induced proximity effect cod cyclooctadiene cont continue

Cp cyclopentadienyl

Cy cyclohexyl d doublet (NMR)

δ chemical shift in parts per million downfield from tetramethylsilane

Δ heat

xiii dba dibenzylideneacetone

DCM dichloromethane

DMA N,N-dimethylaceteamide

DMF N,N-dimethylformamide

DMPU 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidone

DMS dimethylsilyl

DMSO dimethylsulfoxide e- electron(s)

Et ethyl equiv equivalent(s)

ESI electrospray ionization (mass spectroscopy) g gram(s)

GC gas chromatography h hour(s)

H+ Acid

HOAc acetic acid

Hz hertz

J coupling constant in hertz

KOt-Bu potassium-tert-butoxide

L liter(s), ligand m mutiplet (NMR), milli

M molar (mol/L), metal, mega

M/C metal on carbon

Me methyl

Mes Mesityl xiv min minute(s) mol mole(s)

MS mass spectroscopy n normal (e.g. unbranched alkyl chain) m/z mass to charge ratio (mass spectroscopy)

Ni nickel

NMR nuclear magnetic resonance o ortho

OAc acetate obsd observed p para

Pd palladium

Ph phenyl ppm parts per million

Py pyridine q quartet (NMR) rt room temperature s singlet (NMR)

S.M. starting material t tert t triplet (NMR)

TEA triethylamine

Tf triflouromethanesulfonyl

TFP tris(2-furyl)phosphine

TMEDA N,N,N’,N’-tetramethylethylenediamine xv

TMS trimethylsilyl

TS transition state

Ts p-toluenesulfonyl

X halogen (e.g. Br), multiple of

xvi

Chapter 1

Introduction

1.1 Background

Transition metal-catalyzed carbon-carbon bond forming reactions are very important tools used by organic chemists. A few of the most widely used are the Stille, Suzuki, Sonagashira,

Negishi and the Heck reactions (Scheme 1.1). Classically, these reactions employ aryl and alkenyl halides. The coupling of alkyl halides containing β-hydrogens has been a problem in cross-coupling chemistry because of fast β–hydride elimination.1 Metal-catalyzed C-C bond forming reactions are important because they have shown wide applicability in the industrial synthesis of fine chemicals, pharmaceutically active compounds, and agricultural chemicals, as well as in natural product synthesis.2 Cross-coupling reactions are also very easy to control by the use of different ligands. By placing ancillary ligands in the coordination sphere of a metal, one can govern the steric, electronic, and physical properties of a coordinated species, thereby affecting the system’s catalytic activity.3 Excluding the Heck reaction, these cross-coupling reactions follow the same general catalytic cycle: oxidative addition, transmetallation, and reductive elimination (Scheme 1.2).4 The Heck mechanism is unique in that the C-C bond forming step is a migratory insertion not a reductive elimination.5

Scheme 1.1. Cross-Coupling Reactions

Scheme 1.2. General Catalytic Cycle

1.2 The Heck Reaction

In this thesis, we will first concentrate on the Heck reaction and our efforts to develop an alkyl Heck reaction. The Heck mechanism is very complex and any one cycle cannot reflect all the possible variants.5 A simplified Heck mechanism consists of a pre-activation step, oxidative addition, migratory insertion, β-elimination and finished by a reductive elimination to regenerate the catalyst (scheme 1.3). The mechanism helps elucidate the problems we confronted, the main

Scheme 1.3. Heck Mechanism

obstacle in developing an alkyl Heck is to be able to control the rate of β-hydride elimination relative to the rate of insertion. There are a few reasons why this problem is difficult to solve.

First, getting the metal to oxidatively add to the alkyl halide is significantly more difficult than the oxidative addition to an aryl or alkenyl halide bond.6 The addition is harder because C(sp3)-X bonds are far more electron rich than C(sp2)-X bonds. The alkyl metal produced is also much less stable then the aryl or alkenyl metal intermediate because of the absence of π-electrons to interact with the empty d-orbitals of the metal. This inherent instability is our next problem and the main cause for β-hydride elimination.1 Greg Fu has shown that alkyl Heck coupling is possible when

Scheme 1.4. Fu’s “Alkyl Heck”

performing the reaction intramolecularly. It is believed that this reaction proceeds because the product of oxidative addition undergoes migratory insertion with the attached olefin faster than

β–hydride elimination, and the insertion product eliminates before it is able to intermolecularly add itself to another olefin (Scheme 1.4).7 We attempted to mimic this using a complex induced proximity effect (CIPE) (Scheme 1.5).8 CIPE has been shown to work for Heck reactions that

Scheme 1.5. Complex Induced Proximity Effect (CIPE)

did not proceed smoothly under typical Heck conditions. 9 Treatment of vinylsilanes with aryl iodide under standard Heck conditions afforded exclusively styrene derivatives, which is a result

5 of a palladium promoted carbon-silicon bond cleavage (Scheme 1.6).10 Yoshida et al. have shown that the complexation between palladium and a pyridyl group can overcome this problem.9

Scheme 1.6. Yoshida’s CIPE “Proof of Principle”

We attempted to use this same concept with a variety of coordinating atoms. Palladium and nickel were tested as possible catalysts under many different conditions but neither was able to generate the wanted product in appreciable yields. Further manipulation of the oxidative addition and migratory insertion steps are needed in order to achieve an alkyl Heck.

1.3 Palladacycle

Continuing with our theme of transition-metal organometallic chemistry, we will also discuss an interesting new palladacycle A (Figure 1.1) that was synthesized by our group.

Cyclometallated compounds were first discovered in 1963 by Kleinman and Dubec,11 who reacted azobenzene with NiCp2 to give rise to the first cyclometallated complex (Scheme 1.7.),

Figure 1.1. Palladacycle A

Scheme 1.7. First Cyclometallated Complex

which was characterized by 1H NMR spectroscopy and elemental analysis. A palladacycle is defined as a compound containing at least one Pd-C bond and one or more intramolecularly coordinated neutral donor atoms (N, P, As, O, Se, or S).12 There are two types of palladacycles: anionic four-electron donor and six-electron pincer type donor systems (Figure 1.2). Palladacycle

A is a four-electron donor complex. It is also interesting to note that most four-electron complexes exist as dimers and that the metalated carbon is usually an aromatic sp2 carbon.13

Organopalladium compounds are especially popular because they are relatively easy to prepare, exceedingly versatile synthetic tools, and compatible with most functional groups.14

Palladacycles have also

Figure 1.2. Types of Palladacycles

been shown to be very potent precatalysts for organometallic cross-coupling reactions.15 Hartwig discovered a related palladacycle B (Figure 1.3) in 2005 while working on the monoarylation of nitriles (Scheme 1.8). 16 While performing a 31P NMR study on the latter reaction, they saw a

Figure 1.3. Palladacycle B

dominant peak at -7.8 ppm., which was attributed to the phosphines in palladacycle B. They attempted similar monoarylations with preformed B as the catalyst instead of the in-situ formation with Pd(OAc)2 and P(t-Bu)3, however the reactions did not proceed with comparable yields or rates.

Scheme 1.8. Monoarylation of nitriles

Complex B was then used with an extra equivalent of P(t-Bu)3, which gave rise to similar yields and rates as the reaction catalyzed with Pd(OAc)2 and P(t-Bu)3 in a 1:2 ratio. These results sparked our interest in the mechanism of this reaction and the reactive intermediates therein. We found that with B made an extra equivalent of P(t-Bu)3 will provide A. We therefore wanted to investigate if A was the precatalyst or an intermediate in reactions that involve Pd(OAc)2 and

P(t-Bu)3 in a 1:2 ratio. Results and observations made while working toward an alkyl Heck reaction and all studies done on palladacycle A will be discussed in the proceeding chapters.

Chapter 2

Progress toward an alkyl Heck reaction

2.1 Background Information

As discussed in chapter 1, the Heck reaction is a powerful tool for organic chemists, and expanding the scope of this reaction to include alkyl substrates would be exceedingly useful. The work by Yoshida showed that the complex induced proximity effect can have a big influence on where the Pd is inserted into the double bond. As a result we decided to see if we could use the same effect to bring our double bond in close proximity to the oxidative addition product

(Scheme 2.1).

Scheme 2.1. CIPE 10

The first problem that we encountered was to isolate the product from the reaction mixture. We therefore decided to make the product by other means in order to be able to analyze the reactions by GC. After synthesizing the product a variety of different Pd and Ni sources as well as ligands, solvents and bases were investigated but were never able to make the desired product. Herein, shall be discussed our efforts and any conclusions drawn from our work.

2.2 Synthesis of the Heck Product

Our first attempt to make the Heck product was not successful. We envisioned starting from 2-bromopyridine and making 2-trimethylsilylpyridine, which we were then going to deprotonate and add to 4-phenylbutanal, and finish with an acid-catalyzed dehydration

Scheme 2.2. First Proposed Route to the Heck Product

(Scheme 2.2). We were able to make the 2-trimethylsilylpyridine albeit in low yields (32%). We then attempted to couple the 2-TMS pyridine to 4-phenylbutanal but the reaction failed. We believed the main problem arose from competitive deprotonation between the 6-position on the pyridine and the methyl group of the TMS.

We then attempted a similar route, which was also ineffective. Here we would make a bis-dimethylsilylpyridalmethane compound C and directly turn it into the product through a known procedure (Scheme 2.3).17 We were able to make the two silylated pyridines but we were

Scheme 2.3. Second Proposed Route to the Heck Product

never able to couple them together to give C. Since these routes were proving to be very troublesome, we abandoned them and went a completely different way.

The route that worked started with a hydrosilylation of terminal the alkynes, followed by reacting the corresponding D and D’ alkenes with 2-lithiopyridine to afford the desired Heck

Scheme 2.4. Final Route to the Heck Products 12

products (Scheme 2.4). The synthesis of the Heck products was started by testing a few different metals that are known to hydrosilate alkynes and give the trans-product.18, 19, 20, 21Platinic acid did not give any conversion regardless of the reaction time and catalyst loading (Entries 1-3, Table

2.1). We moved on to use palladium, platinum and rhodium on carbon. Initially by GC palladium and platinum on carbon both gave 100% conversions with platinum providing a higher E:Z ratio

(Entries 5 &7, Table 2.1). Later, Wilkinson’s catalyst was found to afford a slightly lower conversion but a higher E:Z ratio (Entry 10, Table 2.1). An accurate yield was not able to be calculated because the intermediate chlorosilane is very reactive therefore it was distilled and immediately reacted with the lithiated pyridine. This gave our desired products for the Heck reactions. The same synthetic steps were applied to the aryl alkyne and heptyne, to give the desired synthetic targets for the Heck reaction, in 67% and 57% respectively over 2 steps

(Scheme 2.5).

Table 2.1. Hydrosilation Results

S =

S’ =

Scheme 2.5. Heck Products 14

2.3 Results and Discussion

Our initial goal was to test transition metal complexes known to mediate Heck reactions an in effort to find a system that would allow us to use alkyl halides as the electrophile. A variety of metals, ligands, and coordinating groups were used but our efforts were essentially fruitless in developing an alkyl Heck. Nonetheless, we were able to perform reductive alkylation and the best results were obtained when using Ni(cod)2, PPh3, and pyridyl alkenes.

2.4 Ethereal Coordinating Alkenes

In addition to the pyridyl alkenes, unsaturated thioethers, and an ether were also tried.

They did not provide the sought after products. Our results are summarized in the tables and schemes below. An assortment of palladium and nickel conditions was attempted on thioether E

(Table 2.2). Nickel was attempted because similar conditions were established to work for

Table 2.2. Thioether Resuts

the coupling of styrene and bromocyclohexane by Lebedev in 1988.22 The only observable product was the alkene, which came from β-hydride elimination of the oxidatively added metal- alkyl-halide intermediate. The fact that only the elimination product was observed meant that the

CIPE was not influencing the insertion step, even though the sulfur had to be coordinated because sulfides are known to stabilize Pd(0) intermediates. 23 Our group has shown that aryl sulfides can be used as ligands in cross-coupling reactions. This led to attempting “ligand-free” conditions were the thioether would also serve as the ligand therefore ensuring that the alkene will be in close proximity to the oxidative addition product. These conditions did not lead to the product,

Table 2.3. De-allylation of Thioether E

but did afford the deallylation product and isomerization of E (Table 2.3). This was not completely surprising because the thiol protecting group N-Allyloxycarbonyl-N-[2,3,5,6-

17 tetrafluoro-4-(phenylthio)phenyl]aminomethyl (Fsam) is selectively removed by a palladium- catalyzed allylic cleavage in the presence of a nucleophile.24 Palladium is also known to easily deprotect allylic ethers and afford the alcohols.25 In order to avoid the de-allylation product, the double bond was move further away from the sulfur. Astonishingly the same product was afforded when pent-4-enyl(phenyl)sulfane H was used (Scheme 2.6). Next, nickel and palladium conditions were tried on ether J (Figure 2.1). Unfortunately these reactions also failed. Only starting material and β-hydride elimination products were observed. No other unsaturated ethers were tried because of the facile de-allylations that these compounds go through if the unsaturation is moved any closer to the oxygen.

Scheme 2.6. De-allylation of Thioether H

Figure 2.1. Ether J 18

2.5 Pyridyl Coordinating Alkenes

All the pyridyl groups tested are shown below (Figure 2.2). Our research began using alkene K because Yoshida had shown its capability as a directing group in standard Heck

9 reactions. The 2-PyMe2Si group on K is not only used for coordination, it also serves as a phase tag to facilitate purification.26 Our efforts to get the Heck product with this alkene were

Figure 2.2. Pyridyl Alkenes K, L, M, and N

unsuccessful. The alkenes that gave the best results were alkenes M and N. With alkenes K and

L, nothing was ever added over the double bond and usually only the β-hydride elimination product and starting materials were observed by GC. The conditions tried for alkenes K and L are summarized below (Tables 2.4 & 2.5).

Table 2.4. Vinyl-pyridine Results

There was finally some success when testing alkenes M and N, from the results it was concluded that M and N worked better because they make a more favorable transition state than L

Table 2.5 Results for Alkene K

(Figure 2.3). Surprisingly the expected Heck product was not being formed. Instead, a reductive alkylation was occurring on the alkene to afford O like products (Scheme 2.7). When it comes to

Heck chemistry, trends in reactivity and selectivity are very unpredictable. Frequently a small 21 change in substrate structure, nature of base, ligand, temperature or pressure can lead to unpredictable results.5 Therefore, the conditions were optimized by varying ligands, bases, solvents and metal sources.

Figure 2.3. Proposed TS‡

Scheme 2.7. Reductive Alkylation

2.6 Mechanistic Considerations

The reaction is assumed to follow the proposed mechanism provided below (Scheme

2.8). Before the alkylating mechanism can commence, a double bond migration must occur first.

This is derived from the fact that the alkylation occurs on carbon 8 as opposed to carbon 10

(Scheme 2.7), and that when the double bond isomerization is stopped so is the reaction. The first

22 step in the alkylation is complexation of II and Ni(0) to afford the proposed TS N (Figure 2.3).

That is followed by the oxidative addition of an alkyl halide to give III. Then a migratory insertion and protonation occur to give IV. We are still unsure of the proton source but because the yields are higher than fifty percent, we do not believe it solely comes from the β-hydrogen

Scheme 2.8. Proposed Mechanism

elimination of the alkyl haldie. The Ni1+ in IV is then reduced by either Zn(0) or Zn(I)Br to

Ni(0), which is stabilized by the ligand, alkene and Py present in the reaction. Ni is also known to

24 perform radical type reactions27 but the fact that no bicyclohexyl was observed pointed us toward a non-radical mechanism. It is also important to note that no Heck type products were formed.

2.7 Solvent Selection

The optimization began with a solvent screening, which included a range of solvents varying in both polarity and boiling point. The more polar solvents gave better results with the exceptions of Et2O and DMF (Entries 1-4 & 7 &8, Table 2.6). Both of the non-polar solvents

(toluene and pentane) gave either trace amounts of product O or none at all.

Table 2.6. Solvent Screening

2.8 Base Selection

After concluding that THF was the best solvent for our system we moved on to bases.

Many different bases are known to successfully promote the Heck reaction. 28 Bases can vary by strength, size and solubility but its main purpose if to scavenge the PdH intermediate because re- addition to the double bond may occur, which will lead to a variety of isomeric products.3 The base screening showed that pyridine worked best with our system (Entry 8, Table 2.7). As far as base strength goes, it seems like weaker bases are preferred. This can be seen when switching from pyridine to TMEDA or TEA, and when going from sodium-acetate to sodium-phenoxide or tri-potassium phosphate (Entries 3, 4, 5, 6, 7, & 8, Table 2.7). Bulky bases such as (Cy)3NMe and Cs2CO3 did not afford any product and only isomerization of N was observed (Entry 1 & 2,

Table 2.7).

Table 2.7. Base Screening

After concluding that pyridine was the best base, we wanted to see if varying the amount of base would change the efficiency of the reaction. We took the bases that showed product formation and varied their equivalents. The experiment shows that using 2 equivalents of pyridine gave the highest yield, 1 equivalent produced a lower yield and 3 equivalents did not change the yield (Entries 1-3, Table 2.8). Other than pyridine, 2 equivalents of TMEDA had the best result, any more is detrimental (Entries 4 & 5, Table 2.8).

Table 2.8. Further Base Optimization

2.9 Phosphine Selection

The ligand’s main purpose in the Heck reaction is to stabilize palladium in its zero

3 oxidation state as stable PdL3 and PdL4 complexes. Ligands vary in coordination strength, due to their size and electronic properties. Often in Heck chemistry brand name precious ligands which work miracles in sophisticated transformations fail in the simplest cases. Our ligand screening revealed that 20 mol% of PPh3 worked the best (Entry 3, Table 2.9), from these initial results it is hard to conclude if stronger (Entries 4 & 7, Table 2.9) or weaker (Entries 5, 6 & 8, Table 2.9) coordination is superior because both ways gave lower yield then PPh3.

Table 2.9. Ligand Screening

2.10 Further Optimization

Before realizing that a reductive alkylation was taking place instead of a Heck, the isomerization of the starting alkene was believed to be negatively affecting the yield. In an effort to stop isomerization, silver salts were added. Hallberg et al. have shown that adding silver salt suppresses double bond isomerization in the Heck arylation of 1-(Methoxycarbonyl)-2,5- dihydropyrrole.29 30 Adding the silver salts did in fact reduce the isomerization of the double bond but it also drastically reduced the yield (table 2.10). This lead us to the transition state proposed earlier where N must isomerizes before it can react (figure 2.3).

Table 2.10. Suppression of Double Bond Isomerization

A few different nickel and palladium conditions were attempted. The palladium conditions employed did not afford any product (Entries 4-6, Table 2.11); the same conditions with an added equivalent of Zn(0) were also unsuccessful. The conditions we established to give the best result also led to no product formation when Zn(0) was not added (Entry 2 Table 2.11).

The preformed nickel catalyst (Entries 1 & 3, Table 2.11) did not perform as well as the in-situ formed catalyst (Entry 3, Table 2.9).

Table 2.11. A Few Different Metal Sources

Due to time restrictions in the lab only a few experiments were performed on alkene M.

After finding out that isomerization was needed in order to make the reaction work, a shorter alkyl chain was used to place the double bond where it is needed from the onset of the reaction.

The preliminary results looked very promising (Table 2.12). By monitoring these reactions by GC we were able to see that the product to SM ratio plateaus faster with bromohexane than with bromocyclohexane when M is the alkene.

Table 2.12. Results with Alkene M

2.11 Conclusion

An alkyl Heck reaction was not achieved but an interesting reductive alkylation has been discovered. In order to achieve an alkyl Heck reaction, more control over the rate of β-hydride elimination relative to the rate of insertion is needed. On a good note there is much more optimization that can be done on the reductive alkylations and a scope for this reaction needs to be established. Thus far Ni(cod)2 (5 mol%), PPh3 (20 mol%), and Py (2 equiv) work the best and afford the reductive alkylation of Alkene N in a 60% yield.

Chapter 3

Palladacycle

3.1 Background

Our initial interest in this area came from work done by Brunel.31 He investigated the mechanistic aspects of a selective homogenous palladium-catalyzed reduction of alkenes. In his work he only considered Pd[P(t-Bu)3]2 as the active Pd species, but it is known that when

32 Pd(OAc)2 and P(t-Bu)3 are used as the catalyst they can make at least a few different Pd species.

Hartwig’s work on the monoarylation of nitriles also contributed to our interest in palladacycle A

(Figure 1.1). We thought that it would be interesting to see why their reactions did not proceed with B, but did when you added B and an extra equivalent of tri-tertbutylphosphine. In addition to monoarylations, palladium acetate and tri-tertbutylphosphine in a 1:2 ratio are a very common combination for a variety of cross-coupling reactions.33, 34, 35 Because of this, a plan was set forth to test the reactivity of our palladacycle. The first reaction investigated was the amination of aryl halides. This reaction was interesting to us because amination reactions are believed to follow a

Pd(0)/Pd(II) mechanism (Scheme 3.2) 36. If our palladacycle works then that would either mean that aminations can possibly follow a Pd(II)/Pd(IV) mechanism or that our palladacycle can serve as a useful precatalyst that give rise to active, stable Pd(0) species.37

3.2 Results and Discussion

Research on this topic began by testing different ratios of palladium(II)acetate and tri-tertbutylphosphine in an effort to see which combination would afford palladacycle A. After getting the optimal conditions to afford A, we moved on to one of the original goals; to see if B is the active catalyst in reactions catalyzed by Pd(OAc)2 and P(t-Bu)3. With regard to monoarylation reactions we found that A was not the active catalyst but it was a precursor that provided the active catalyst through a series of oxidative additions and reductive eliminations. In terms of other cross-coupling reactions it was never established if A was the active catalyst but it did catalyze many of the same reactions.

3.3 Synthesis of Palladacycle A

Our work began with making B according to Hartwig’s procedure, which gave us the sharp singlet reported at -7.8 ppm. After adding an extra equivalent of P(t-Bu)3 and monitoring the reaction by 31P NMR, five broad peaks were observed. Alarmingly, this was a spectrum of A with some free phosphine present. It was surprising that this was A because upon first inspection of the 31P NMR, one would never think that it was a single structure, as broad peaks are not usually characteristics of palladacycles. In order to find out exactly how many equivalents of P(t-

Bu)3 were needed to make palladacycle A, one through four equivalents of P(t-Bu)3 were reacted

31 with Pd(OAc)2, and monitored by P NMR. We found that the optimal ratio to get the cyclometallated compound was 1:2 Pd(OAc)2: P(t-Bu)3. While trying to figure out the best ratio we made a few different findings. If you react Pd(OAc)2 and P(t-Bu)3 in a 1:1 ratio without heating a mixture of A and B is afforded, ( 1, Figure 3.1). Anything more than 2 equivalents of phosphine were found to give A with a lot of free phosphine (Figure 3.2). Also the mixture of A

34 and B that is afforded when doing the 1:1 experiment, will almost completely go to A by adding an extra equivalent of P(t-Bu)3 (2, Figure 3.1). Our highest isolated yield of A was 80%.

Palladacycle B

Palladacycle A

Free P(t-Bu)3

Palladacycle A

Palladacycle B

Free P(t-Bu)3

1= Pd(OAc)2 and P(t-Bu)3 1:1, 2 = 1 + 1 equiv of P(t-Bu)

Figure 3.1. A & B Mixture Goes to A 35

Palladacycle A

Palladacycle B

Free P(t-Bu)3

2 2

Free P(t-Bu)3 Palladacycle A

Palladacycle B

Palladacycle A

Free P(t-Bu)3 Palladacycle B

1 = Pd(OAc)2 and P(t-Bu)3 1:2, 2 = Pd(OAc)2 and P(t-Bu)3 1:3 3 = Pd(OAc)2 and P(t-Bu)3 1:4

Figure 3.2. 2-4 Equivalents of P(t-Bu)3 with Pd(OAc)2 36

3.4 Variable Temperature NMR Experiments

In an attempt to get the NMR structures to look more defined, a variable temperature

NMR experiment was conducted on A. It was observed that the broad peaks were due to the labile bonds found in the palladacycle at 23 ºC. When we cooled the instrument down to -30 ºC, we were able to observe sharp doublets in the 31P NMR instead of the very broad doublet seen at room temperature (Scheme 3.3). They also consistently became sharper at lower temperatures.

The 1H NMR was also very interesting. At room temperature there was only one peak present for the methyl group on the two different acetic acids, but when A was cooled the peaks begin to shift and separate from each other. They begin to separate at -30 ºC, and are very defined by -45

ºC (Figure 3.4).

1 = 23 oC 2 = -30 ºC, 3 = -45 ºC, 4 = -60 ºC

Figure 3.3. Variable Temperature 31P NMR 38

Only one peak for both sets of methyl hydrogens

They begin to separate at -30 o C

Completely separated at -45 o C

1 = 23 ºC, 2 = -30 ºC, 3 = -45, * 1 in C6D6, 2 and 3 in C7D8

Figure 3.4. Variable Temperature 1H NMR

3.5 Amination Reactions

The first reaction tested to see if palladacycle A could be the active catalyst in reactions catalyzed by Pd(OAc)2 and P(t-Bu)3 was the amination of aryl halides by secondary amines

(Scheme 3.1). In order for palladacycle A to be considered the active catalyst, it must be catalytically competent, which means it must either react as fast as, or faster than when Pd(OAc)2 and P(t-Bu)3 are used independently. This experiment would be significant because amination reactions are believed to go through a Pd(0)/Pd(II) cycle (Scheme 3.2)36 and if palladacycle A

Scheme 3.1. Amination Reaction

Scheme 3.2. Amination Mechanism

proved to be the active catalyst it would rule out the Pd(0)/Pd(II) mechanism, because A is at least Pd(I), from the carbon bond. Our results show that palladacycle A is not the active catalyst.

The reactions proceeded with similar yields (Table 3.1) but the rates where slower (Figure 3.5). It can clearly be seen in the time trial that the reactions catalyzed by the palladacycle B required a longer preactivation step than when the catalyst was made in-situ by Pd(OAc)2 and P(t-Bu)3

(Series 1 & 3-5, Figure 3.5). The catalyst made by Pd(dba)2 and P(t-Bu)3 on the other hand was slower in all cases when compared to palladacycle A (Series 2 and 6-8, Figure 3.1). Oddly the ligand to metal ratio did not make much of a difference in the case of Pd(OAc)2 and P(t-Bu)3. The rates were virtually consistent regardless of the ratio (1:1, 2:1, or 3:1) (Series 3-6, Figure 3.5).

Table 3.1. Amination Results

Conversely Pd(dba)2 and P(t-Bu)3 showed a large effect when increasing the ligand to metal ratio.

When the ratio was 1:1 the rates were similar to that of the palladacycle A, but when the ratio is increased to either 2:1 or 3:1 the rate droped dramatically (Series 1 and 6-8, Figure 3.5). The two preformed catalyst had similar reaction rates throughout the reaction except for the first 20 minutes, which could be rationalized as the time needed for our palladacycle to generate the active Pd(0) catalyst (Series 1 and 2, Figure 3.5).

Hartwig and co-workers have also shown that Pd(OAc)2 and P(t-Bu)3 can catalyze the amination of ortho-substituted aryl halides by secondary amines in high yields at rt (Table 3.2).38

They stated that when they added 2 or 4 equivalents of phosphine to the reactions, they proceeded much slower. This was also seen in our group. All of the reactions done with a preformed catalyst

42 generated from Pd(OAc)2 and P(t-Bu)3 in a 1:2 ratio did not afford yields comparable to

Hartwig’s experiments.

Reaction rates

5.00 8383 4.50 Series Catalyst 4.0080 80 1 Pd(P(Pd(P(tBu)3)2t-Bu) ) 3.50 3 2 2 Pd Cycle A 3.0075 75 3 Pd(OAc)Pd(Oac)2,2 ,P(tBu)3 P(t-Bu) 2%3 2% 2.50 4 Pd(OAc)Pd(Oac)2,2 ,P(tBu)3 P(t-Bu) 4%3 4% 2.0067 67 5 Pd(OAc)Pd(Oac)2,2 ,P(tBu)3 P(t-Bu) 6%3 6% 1.50 6 Pd(dba)Pd(dba)2,2, P(tBu)3P(t-Bu) 32% 2% 1.005050 7 Pd(dba)Pd(dba)2,2, P(tBu)3P(t-Bu) 34% 4% 8 Pd(dba)Pd(dba)2,, P(tBu)3P(t-Bu) 6% 6% 0.50 2 3 % Conversion to to Product Conversion % 0.0000 -0.50 0 120 240 360 480 Time (min)

Figure 3.5. Amination Time Trial

Table 3.2. Hartwig’s Amination of Ortho-Substituted Aryl Halides

Table 3.3. Amination of Ortho-Substituted Aryl Halides

Palladacycle A did outperform both palladacycle B and Pd(P(t-Bu)3)2 at both higher (Entries 4-6,

Table 3.3) and lower temperatures (Entries 1-3, Table 3.3). From these results, it can be inferred that palladacycle A is not the active catalyst in these reactions, but does provide the active catalyst for these reactions more efficiently than the other two palladium sources we tried.

3.7 Conclusion

In conclusion, we have synthesized an interesting new palladacycle that showed potential as a precatalyst. The highest isolated yield for A was 80%. It was also interesting to see the dynamic nature of A and how the transient nature of the bonds is reduced at lower temperatures.

Chapter 4

Experimental Details

4.1 General Methods

Unless otherwise stated, reactions were conducted in oven-dried glassware under an atmosphere of nitrogen using anhydrous solvents. THF, Et2O, toluene and pentane were passed through activated alumina columns. All reagents were obtained commercially and used as received. Thin- layer chromatography (TLC) was conducted with silica gel UV254 pre-coated plates (0.25mm), and visualized using UV lamps. Silica gel (particle size 40-63 μm) was used for flash chromatography. 1H and 13C NMR spectra are reported relative to deuterated solvent signals or tetramethylsilane. GC analysis was performed on an instrument equipped with FID detectors using a HP-5 (5%-Phenyl)-methylpolysiloxane column. High resolution mass spectra were obtained on a MicrOTOF instrument.

4.2 Chapter 2: Experimental Methods

Reductive alkylations

The metal catalyst (5 mol%), phosphine ligand (20.0 mol%), solvent (1.30 ml) and a stir-bar are added to a small vial inside a glove box and fitted with a septa cap .Once outside the alkene (0.40 mmol), alkyl halide (0.400 mmol), base ( 2.00 equiv), and undecane (1 equiv) as an internal standard are added. The capped vial is then heated at 65 oC for 20 h. When the reaction is complete (by the GC), the reaction is quenched with H2O (10.0 ml). The ogranic layer is then extracted with ether, dried over Na2SO4, and concentrated under vacuo. The concentrated crude mixture is then purified by flash chromatography. All isolated products were judged by 1H NMR spectroscopy.

1 For O: H NMR (400 MHz, CDCl3): δ 0.82 (t, J= 8.1, 3 H), 1.16-1.25 (m, 6

H), 1.31-1.38 (m, 2 H), 1.59-1.74 (m, 6 H), 2.60 (dd, J = 8.4, 13.6 Hz, 1 H),

2.81 (dd, J = 6, 13. 6, 1 H), 7.08 (m, 2 H) 7.55 (td, J = 2, 7.6 Hz, 1 H), 8.52

13 (m, 1 H); C NMR (62 MHz, CDCl3): ppm 11.91, 22.92, 26.86, 26.91, 26.94, 29.41, 29.91,

39.54, 39.67, 45.85, 120.63, 123.53, 135.90, 149.18; ESI HRMS m/z (M + H)+ calcd 218.1903, obsd 218.1911.

1 For Q’: H NMR (250 MHz, CDCl3): δ 0.83 (m, 6 H), 1.27 (m, 10 H),

1.91 (m, 1 H), 2.51 (dd, J = 8.5, 13.3 Hz, 1 H) 2.78 (dd, J = 6, 13.5 Hz,

1 H), 7.07 (m, 2 H), 7.55 (t, J = 7.8 Hz, 1 H) 8.51 (d, J = 5 Hz, 1 H);

ESI HRMS m/z (M + H)+ calcd 206.1903, obsd 206.1902.

Hydrosilations

M/C conditions

M/C (1.50 mg, 3% by weight) and a stir-bar were placed in a septa capped vial under an inert atmosphere. Toluene (1 ml), 5-phenylpentyne (50.0 mg, 0.35 mmol) and CDS (38.25 mg, 0.40 mmol) were added to the vial in order via syringe. The vial was then heated under reflux for 24 h.

The solvent was then removed under vacuo and the product distilled.

Wilkinson’s catalyst conditions18 D & D’

D (E & Z)-chloro(hept-1-enyl)dimethylsilane

In a dry round bottom flask equipped with a stir-bar, Wilkinson’s catalyst (16.4 mg, 17.7X10-3 mmol) was dissolved in toluene (2.50 ml). Then heptyne (0.264 ml,

2.75 mmol) dissolved in toluene (2.5 ml) was added to the solution via syringe. The reaction was then stirred and CDS was added dropwise over 15 min., and let to stir at rt for 24 h. The solvent

48 was then removed under pressure and the products distilled. Spectroscopic data were identical to those published previously.

D’ (E & Z)-chlorodimethyl(5-phenylpent-1-enyl)silane

1 For D’ H NMR (250 MHz, CDCl3): δ 0.48 (s, 6 H) 1.65-1.88 (m, 2 H), 2.09-2.31 (m, 2 H), 2.55-

2.63 (m, 2 H), 5.66- 5.73 (m, 1 H), 6.26 (td, 6, 18.8 Hz, 1 H) 7.13-7.29 (m, 5 H)

Platinic Acid Conditions21

Platinic acid (4.1 mg, 10X10-3 mmol) was dissolved in 2-propanol (.15 ml) and ether (4 ml) in a round bottom flask equipped with a stir-bar and a reflux condenser, under N2. CDS (.287 g, 3.033 mmol) was added to the mixture and heated to reflux. A solution of 5-phenylpentyne (.397 g, 2.75 mmol) in ether (1.5 ml) was added over 10 min. After the addition was complete the mixture was kept under reflux for 4 h. The solvent was then removed under pressure, and analyzed by GC and

1H NMR. No product was ever observed.

Pyridyl Compounds

K 2-dimethyl(vinyl)silylpyridine 9

n-Butyllithium ( .0405 mol, 1.5M in hexane) was added drop-wise to a

solution 2-bromopyridine (7.11 g, .045mol) in ether (30 ml) at -78 oC under

o N2. the solution was stirred at -78 C for 1.5 h. The lithiated pyridine solution was then added to a solution of CDVS (5.66 g, .0469 mol) in ether (15 ml) at -78 oC. After stirring at rt for 1 h, sat.

NaHCO3 was added. the aqueous layer was then extracted with ether. The combined ethereal layer were dried with MgSO4. The volatile liquids were removed under pressure and a subsequent distillation afforded 70% of 2-dimethyl(vinyl)silylpyridine. Spectroscopic data were identical to those published previously.

M Allylpyridine39

i-Bu(chloroformate) (1.1 equiv) in THF (80 mL) was added drop-wise to pyridine-N-oxide (1.0 equiv) in THF (80 mL) at 0 oC. The afforded white suspension was cooled to -50 oC then allyl(zinc)bromide (2 equiv) in THF (50 mL) were added quickly. The solution was then stirred at -50 oC for 30 min (or until there were no more salts present). Followed by 30 min at -78 oC. The solution was then brought up to rt and stirred for an additional 30 min. The reaction was then quenched by ice cold NH4OH (20% aq, 200 mL). The aqueous phase was 50 extracted with Et2O (6 X 50 mL). The combined organic phases were then washed with HCl

(20%, 50 mL). The aqueous phase was then treated with NaOH (20%, until basic by pH paper) and extracted with Et2O ( 6 X 30 mL). The organic layer was the dried with Na2SO4 and purified by flash chromatography (7:1 hexanes: ethyl acetate) to yield M in 45%. Spectroscopic data were identical to those published previously.

N 2-(But-3-enyl)pyridine40

To a solution of 2-picoline (0.186 g, 2 mmol) in dry THF ( 2 ml), under an

o N2 atmosphere at -78 C, was added t-butyllithium (1.235 ml, 2.1 mmol), and the reaction was stirred for 1 h. Then, allyl bromide was added drop-wise at -78 oC over 30 min and stirred overnight at 23 oC. The mixture was extracted with water and EtOAc, the organic layer was dried with Na2SO4, and the solvent evaporated under pressure. Compound N was isolated as yellow oil by flash chromatography (Hex/ EtOAc 8:2) (75%). Spectroscopic data were identical to those published previously.

2-(DMS)pyridine

n-butyllithium ( .0405 mol, 1.5M in hexane) was added drop-wise to a solution

o 2-bromopyridine (7.11 g, .045mol) in ether (30 ml) at -78 C under N2. the solution was stirred at -78 oC for 1.5 h. The lithiated pyridine solution was then added to a solution of CDS (5.66 g, .0469 mol) in ether (15 ml) at -78 oC. After stirring at rt for 1 h, sat.

NaHCO3 was added. the aqueous layer was then extracted with ether. The combined ethereal layers were dried with MgSO4. The volatile liquids were removed under pressure and a 51 subsequent distillation afforded 2-dimethyl(silyl)pyridine. Spectroscopic data were identical to those published previously

2(-TMS)pyridine41

2-Bromopyridine (6.95 g, .044 mol), TMSCl (4.84 g, .044 mol) in THF (35 ml)

was added dropwise to Mg turnings (1.35 g, .052 mol) in THF (20 ml) over 4 h.

After the addition was complete it was stirred for 8 h., then refluxed for 2 h. THF was then removed under pressure. Dry benzene (25 ml) was added and brought to reflux again for 1 h. The

THF-benzene mixture was the decanted. Benzene was added to the reaction again and refluxed for 1 h. The benzene procedure was repeated 3X’s. The benzene extracts were collected and fractionally distilled to afford 2-(TMS)pyridine in 32%. Spectroscopic data were identical to those published previously.

n-Butyllithium ( .0405 mol, 1.5M in hexane) was added drop-wise to a

solution 2-bromopyridine (7.11 g, .045mol) in ether (30 ml) at -78 oC under

1 For S: H NMR (250 MHz, CDCl3): δ 0.36 (s, 6 H), 0.78- 0.96

(m, 3 H), 1.23- 1.45 (m, 6 H), 2.03- 2.17 (m, 2 H), 5.79 (d, 18.5

Hz, 1 H), 6.17 (td, 6.3, 18.8 Hz, 1 H), 7.13- 7.18 (m, 1 H), 7.46- 7.58 (m, 2 H), 8.75- 8.77 (m, 1

H).

1 For S’: H NMR (400 MHz, CDCl3): δ 0.38 (s, 6 H), 1.72-1.79

(m, 2 H), 2.18-2.24 (m, 2 H), 2.62 (t, 8 Hz, 2 H), 5.84 (dt, 18.8,

1.6 Hz, 1 H) 6.20 (td, 6.4, 18.4 Hz, 1 H), 7.16- 7.19 (m, 4 H),

7.25- 7.29 (m, 2 H), 7.49- 7.51 (m, 1 H), 7.54-7.59 (m, 1 H), 8.77-8.78 (m 1 H).

Thioethers

E Allyl(phenyl)silane42

-2 o To KOt-Bu (9.17 g, 9.00X10 mol) in dry THF (100 mL) at 0 C under N2, thiophenol (8.50 mL, 9.00X10-2 mol) was added drop-wise. The resulting white precipitate was stirred at 0 oC for 30 min then at rt for 2 h. The solution was the cooled back down to 0 oC. and allyl chloride (10.0 mL, 0.130 mol) in dry THF (100 mL) was added over 30 min. The reaction was then brought up to rt over 30 min. After 2 h the solid was removed by filtration and washed with Et2O. The organic phase was then washed with NaOH (1M), water, brine, and dried over

Na2SO4, filtered and concentrated under vacuum. The resulting yellow oil was purified by flash chromatography (hexanes) yielded 3.00 g (83%) of sulfane E. Spectroscopic data were identical to those published previously.

H Pent-4-enyl(phenyl)sulfane43

6-bromo-1-pentene (1.52 g, 10.2 mmol) was mixed with thiophenol (1.05 mL, 10.

2 mmol) and DBU (1.52 mL, 10.2 mmol) in dry benzene (30 mL) with stirring at rt under N2. A precipitate formed immediately . After 4 h, the solid was removed by filtration and washed with DCM. The DCM solution was washed with dilute aqueous sodium chloride solution.

The benzene filtrate was combined with the dichloromethane phase and dried with Na2SO4, and the solvents were removed under vacuum to yield a clear oil (1.57 g, 86% yield). Spectroscopic data were identical to those published previously.

4.3 Chapter 3: Experimental Methods

Palladacycle B16

A mixture of Pd(OAc)2 (112 mg, 0.500 mmol) and P(t-Bu)3

(101 mg, 0.500 mmol) in toluene (5 mL) was heated at 90 °C for 10 min. The mixture was then cooled to rt, and the volatile materials were evaporated under vacuum. The residue was dissolved in ether and filtered through Celite. The clear filtrate was then concentrated until solid began to form and was then cooled at –35 oC for 12 h. The supernatant was removed by pipette, and the solid was washed with pentane and dried under vacuum to give complex B as white solid (43 mg, 20%). Spectroscopic data were identical to those published previously.

Palladacycle A

A mixture of Pd(OAc)2 (112 mg. 0.500 mmol) and P(t-Bu)3 (202 mg, 1.00 mmol) in THF (10 mL) was stirred at rt for 24 h. The mixture was then filtered through Celite and the solvent removed under vacuum. The crude yellowish solid was then recrystallized from either

1 Et2O or pentane to yield palladacycle A (80%) as a white crystalline solid. H NMR (400 MHz, toluene- d8, -60 oC): δ 1.02 (s, 2 H), 1.20-1.40 (m, 51 H), 1.95 (s, 3 H), 2.32 (s, 3 H), 15.19 (s, 1

13 H); C NMR (100 MHz, C6D6): ppm 128.7, 128.4, 128.2, 33.2, 32.6, 32.5; IR (KBr pellet) ν =

3420, 2900, 2374, 2345, 1944, 1735, 1702, 1560, 1409, 1271,1171,1020,931 cm-1. Crystal data is also provided later.

Amination reactions

In a drybox, aryl halide (1.00-1.10 mmol), amine (1.00 mmol), Pd(dba)2, Pd(OAc)2, Pd[P(t-Bu)3]2 or palladacycles A & B (0.01-0.02 mmol), tri-tert-butylphosphine (only when using Pd(dba)2 and

Pd(OAc)2) (1.6-3.2 mg, 0.008-0.016 mmol, 0.8 eq/Pd), and Nat-OBu (144 mg, 1.50 mmol) were weighed directly into a screw cap vial. A stir bar was added followed by 1.0-2.0 mL of toluene to give a purple mixture. The vial was removed from the dry-box, and the mixture was stirred at rt

(23 oC). The reaction was monitored by thin-layer chromatography or GC. After complete consumption of starting materials, the resulting thick brown suspension was adsorbed onto silica gel and purified by flash chromatography. Spectroscopic data were identical to those published previously.

Appendix

NMR Spectra

1H NMR A

13C NMR A

1H NMR of D

1H NMR of S

1H NMR of D’

1H NMR of S’

1H NMR of O

1H NMR of Q’

Crystal Data

Experimental

The crystal used for data collection was a colorless rectangular rod. Examination of the diffraction pattern on a Nonius Kappa CCD diffractometer indicated a monoclinic crystal system. All work was done at 200 K using an Oxford Cryosystems Cryostream Cooler. The data collection strategy was set up to measure a quadrant of reciprocal space with a redundancy factor of 3.9, which means that 90% of the reflections were measured at least 3.9 times. Phi and omega scans with a frame width of 1.0˚ were used. Data integration was done with Denzo44, and scaling and merging of the data was done with Scalepack44. Merging the data and averaging the symmetry equivalent reflections resulted in an Rint value of 0.042.

The position of the Pd atom was found by the Patterson method in SHELXS-97.45 The rest of the molecule was located by standard Fourier methods. Full-matrix least-squares refinements based on F2 were performed in SHELXL-9746, as incorporated in the WinGX package.47 The asymmetric unit contains the Pd complex and a solvent molecule of acetic acid. This acetic acid molecule appears to be disordered over two sites, and this was modeled with atoms O(1a), O(2a), C(1a) and C(2a) for one site and atoms O(1b), O(2b), C(1a) and C(2b) for the second site, with atom C(1a) common to both sites. Only C(1a) was refined anisotropically; the other atoms were kept isotropic. No attempt was made to add hydrogen atoms to this disordered model.

For each methyl group, the hydrogen atoms were added at calculated positions using a riding model with U(H) = 1.5*Ueq(bonded carbon atom). For the C(26) methyl group, the torsion angle which defines the orientation of this group about the C-C bond was refined. The remaining hydrogen atoms were included in the model at calculated positions using a riding model with U(H) = 1.2 * Ueq(attached atom). The final refinement cycle was based on 7487 intensities, and 315 variables, and resulted in agreement factors of R1(F) = 0.057 and wR2(F2) = 0.100. For the subset of data with I > 2*sigma(I), the R1(F) value is 0.037 for 5784 reflections. The final difference electron density map contains maximum and minimum peak heights of 0.74 and -0.49 e/Ǻ3. Neutral atom scattering factors were used and include terms for anomalous dispersion.48

Data

Crystallographic details for palladacycle A

Molecular formula C26 H56 O2 P2 Pd + CH3COOH

Formula weight 629.10

Temperature 200(2) K

Wavelength 0.71073 Å

Crystal system monoclinic

Space group P21/n

Unit cell dimensions a = 8.5090(1) Å

b = 24.1146(2) Å

c = 16.0237(2) Å

= 93.2157(4)°

Volume 3282.74(6) Å3

Z 4

Density (calculated) 1.273 Mg/m3

Absorption coefficient 0.691 mm-1

F(000) 1344

Crystal size 0.31 x 0.15 x 0.15 mm3

Theta range for data collection 2.12 to 27.47°

Index ranges -10<=h<=10, -31<=k<=31, -20<=l<=20

Reflections collected 53438

Independent reflections 7487 [R(int) = 0.042]

Completeness to theta = 27.47° 99.7 % 68

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 7487 / 0 / 315

Goodness-of-fit on F2 1.030

Final R indices [I>2sigma(I)] R1 = 0.0373, wR2 = 0.0923

R indices (all data) R1 = 0.0570, wR2 = 0.0998

Largest diff. peak and hole 0.737 and -0.486 e/Å3

Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103) for palladacycle A. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

______

x y z U(eq)

______

C(1) 7880(4) 9074(1) 10024(2) 55(1)

C(2) 7716(4) 9387(1) 9174(2) 51(1)

C(3) 9621(5) 8973(2) 10223(2) 70(1)

C(4) 7219(6) 9378(2) 10772(2) 85(1)

C(5) 7592(4) 7783(1) 10035(2) 47(1)

C(6) 9271(4) 7683(2) 9759(2) 59(1)

C(7) 6591(5) 7293(2) 9716(3) 74(1)

C(8) 7606(5) 7796(2) 10993(2) 67(1)

C(9) 4630(4) 8523(2) 9626(2) 64(1)

C(10) 4074(5) 9106(2) 9350(3) 87(2)

C(11) 4049(5) 8390(2) 10492(3) 85(2)

C(12) 3836(4) 8125(2) 8979(3) 91(2)

C(13) 10138(3) 9330(2) 6883(2) 53(1)

C(14) 10791(4) 8756(2) 7120(3) 72(1)

C(15) 10668(4) 9502(2) 6025(2) 75(1)

C(16) 10898(5) 9734(2) 7531(3) 87(2)

C(17) 7176(5) 10079(2) 7010(2) 59(1)

C(18) 7776(5) 10454(2) 6306(3) 77(1)

C(19) 7581(7) 10378(2) 7825(3) 96(2) 70

C(20) 5351(5) 10061(2) 6922(3) 83(1)

C(21) 6920(3) 8977(1) 6048(2) 45(1)

C(22) 5260(4) 8785(2) 6279(2) 59(1)

C(23) 7811(5) 8450(2) 5829(2) 61(1)

C(24) 6741(5) 9335(2) 5254(2) 68(1)

C(25) 7706(4) 7590(1) 7562(2) 51(1)

C(26) 6873(6) 7065(2) 7281(3) 81(1)

O(1) 6850(3) 8006(1) 7648(1) 49(1)

O(2) 9156(3) 7596(1) 7680(2) 84(1)

P(1) 6840(1) 8460(1) 9558(1) 39(1)

P(2) 7925(1) 9325(1) 7016(1) 35(1)

Pd 7437(1) 8777(1) 8273(1) 32(1)

C(1A) 11682(6) 6552(2) 8082(4) 96(2)

O(1A) 11499(9) 7057(3) 7779(5) 81(2)*

O(2A) 10400(9) 6477(3) 8622(5) 91(3)*

C(2A) 12587(9) 6066(4) 7892(5) 48(2)*

O(1B) 12189(12) 7051(4) 8278(6) 156(3)*

O(2B) 10408(7) 6494(2) 7629(4) 89(2)*

C(2B) 13132(9) 6285(3) 8290(5) 65(2)*

*These atoms belong to a disordered acetic acid molecule and were refined isotropically. The occupancy factor for O(1A), O(2A), and C(2A) refined to 0.417(6), and the occupancy factor for

O(1B), O(2B) and C(2B) is 0.583(6).

______

Bond lengths [Å] and angles [°] for palladacycle A

______

C(1)-C(3) 1.516(5)

C(1)-C(4) 1.539(5)

C(1)-C(2) 1.556(4)

C(1)-P(1) 1.860(4)

C(2)-Pd 2.066(3)

C(2)-H(2A) 0.9900

C(2)-H(2B) 0.9900

C(3)-H(3A) 0.9800

C(3)-H(3B) 0.9800

C(3)-H(3C) 0.9800

C(4)-H(4A) 0.9800

C(4)-H(4B) 0.9800

C(4)-H(4C) 0.9800

C(5)-C(7) 1.528(5)

C(5)-C(8) 1.533(5)

C(5)-C(6) 1.538(5)

C(5)-P(1) 1.899(3)

C(6)-H(6A) 0.9800

C(6)-H(6B) 0.9800

C(6)-H(6C) 0.9800

C(7)-H(7A) 0.9800

C(7)-H(7B) 0.9800

C(7)-H(7C) 0.9800

C(8)-H(8A) 0.9800

C(8)-H(8B) 0.9800

C(8)-H(8C) 0.9800

C(9)-C(11) 1.533(5)

C(9)-C(10) 1.540(6)

C(9)-C(12) 1.541(6)

C(9)-P(1) 1.896(3)

C(10)-H(10A) 0.9800

C(10)-H(10B) 0.9800

C(10)-H(10C) 0.9800

C(11)-H(11A) 0.9800

C(11)-H(11B) 0.9800

C(11)-H(11C) 0.9800

C(12)-H(12A) 0.9800

C(12)-H(12B) 0.9800

C(12)-H(12C) 0.9800

C(13)-C(15) 1.529(4)

C(13)-C(14) 1.530(5)

C(13)-C(16) 1.540(5)

C(13)-P(2) 1.907(3)

C(14)-H(14A) 0.9800

C(14)-H(14B) 0.9800

C(14)-H(14C) 0.9800

C(15)-H(15A) 0.9800

C(15)-H(15B) 0.9800

C(15)-H(15C) 0.9800

C(16)-H(16A) 0.9800

C(16)-H(16B) 0.9800

C(16)-H(16C) 0.9800

C(17)-C(19) 1.513(6)

C(17)-C(20) 1.552(5)

C(17)-C(18) 1.554(5)

C(17)-P(2) 1.928(4)

C(18)-H(18A) 0.9800

C(18)-H(18B) 0.9800

C(18)-H(18C) 0.9800

C(19)-H(19A) 0.9800

C(19)-H(19B) 0.9800

C(19)-H(19C) 0.9800

C(20)-H(20A) 0.9800

C(20)-H(20B) 0.9800

C(20)-H(20C) 0.9800

C(21)-C(23) 1.531(5)

C(21)-C(24) 1.539(4)

C(21)-C(22) 1.550(4)

C(21)-P(2) 1.921(3)

C(22)-H(22A) 0.9800

C(22)-H(22B) 0.9800

C(22)-H(22C) 0.9800

C(23)-H(23A) 0.9800

C(23)-H(23B) 0.9800

C(23)-H(23C) 0.9800

C(24)-H(24A) 0.9800

C(24)-H(24B) 0.9800

C(24)-H(24C) 0.9800

C(25)-O(2) 1.238(4)

C(25)-O(1) 1.252(4)

C(25)-C(26) 1.508(5)

C(26)-H(26A) 0.9800

C(26)-H(26B) 0.9800

C(26)-H(26C) 0.9800

O(1)-Pd 2.156(2)

P(1)-Pd 2.2795(7)

P(2)-Pd 2.4637(7)

C(1A)-O(2B) 1.278(7)

C(1A)-O(1B) 1.311(11)

C(1A)-O(1A) 1.317(9)

C(1A)-C(2B) 1.415(9)

C(1A)-O(2A) 1.441(9)

C(1A)-C(2A) 1.445(10)

C(3)-C(1)-C(4) 108.0(3)

C(3)-C(1)-C(2) 107.5(3)

C(4)-C(1)-C(2) 115.6(3)

C(3)-C(1)-P(1) 113.2(3)

C(4)-C(1)-P(1) 120.4(3)

C(2)-C(1)-P(1) 91.0(2)

C(1)-C(2)-Pd 105.5(2)

C(1)-C(2)-H(2A) 110.6

Pd-C(2)-H(2A) 110.6

C(1)-C(2)-H(2B) 110.6

Pd-C(2)-H(2B) 110.6

H(2A)-C(2)-H(2B) 108.8

C(1)-C(3)-H(3A) 109.5

C(1)-C(3)-H(3B) 109.5

H(3A)-C(3)-H(3B) 109.5

C(1)-C(3)-H(3C) 109.5

H(3A)-C(3)-H(3C) 109.5

H(3B)-C(3)-H(3C) 109.5

C(1)-C(4)-H(4A) 109.5

C(1)-C(4)-H(4B) 109.5

H(4A)-C(4)-H(4B) 109.5

C(1)-C(4)-H(4C) 109.5

H(4A)-C(4)-H(4C) 109.5

H(4B)-C(4)-H(4C) 109.5

C(7)-C(5)-C(8) 108.9(3)

C(7)-C(5)-C(6) 107.0(3)

C(8)-C(5)-C(6) 109.6(3)

C(7)-C(5)-P(1) 111.2(2)

C(8)-C(5)-P(1) 111.7(2)

C(6)-C(5)-P(1) 108.4(2)

C(5)-C(6)-H(6A) 109.5

C(5)-C(6)-H(6B) 109.5

H(6A)-C(6)-H(6B) 109.5

C(5)-C(6)-H(6C) 109.5

H(6A)-C(6)-H(6C) 109.5

H(6B)-C(6)-H(6C) 109.5

C(5)-C(7)-H(7A) 109.5

C(5)-C(7)-H(7B) 109.5

H(7A)-C(7)-H(7B) 109.5

C(5)-C(7)-H(7C) 109.5

H(7A)-C(7)-H(7C) 109.5

H(7B)-C(7)-H(7C) 109.5

C(5)-C(8)-H(8A) 109.5

C(5)-C(8)-H(8B) 109.5

H(8A)-C(8)-H(8B) 109.5

C(5)-C(8)-H(8C) 109.5

H(8A)-C(8)-H(8C) 109.5

H(8B)-C(8)-H(8C) 109.5

C(11)-C(9)-C(10) 109.9(3)

C(11)-C(9)-C(12) 109.1(4)

C(10)-C(9)-C(12) 105.0(3)

C(11)-C(9)-P(1) 114.0(2)

C(10)-C(9)-P(1) 110.3(3)

C(12)-C(9)-P(1) 108.1(3)

C(9)-C(10)-H(10A) 109.5

C(9)-C(10)-H(10B) 109.5

H(10A)-C(10)-H(10B) 109.5

C(9)-C(10)-H(10C) 109.5

H(10A)-C(10)-H(10C) 109.5

H(10B)-C(10)-H(10C) 109.5

C(9)-C(11)-H(11A) 109.5

C(9)-C(11)-H(11B) 109.5

H(11A)-C(11)-H(11B) 109.5

C(9)-C(11)-H(11C) 109.5

H(11A)-C(11)-H(11C) 109.5

H(11B)-C(11)-H(11C) 109.5

C(9)-C(12)-H(12A) 109.5

C(9)-C(12)-H(12B) 109.5

H(12A)-C(12)-H(12B) 109.5

C(9)-C(12)-H(12C) 109.5

H(12A)-C(12)-H(12C) 109.5

H(12B)-C(12)-H(12C) 109.5

C(15)-C(13)-C(14) 110.4(3)

C(15)-C(13)-C(16) 107.5(3)

C(14)-C(13)-C(16) 105.8(3)

C(15)-C(13)-P(2) 116.4(2)

C(14)-C(13)-P(2) 108.3(2)

C(16)-C(13)-P(2) 108.0(3)

C(13)-C(14)-H(14A) 109.5

C(13)-C(14)-H(14B) 109.5

H(14A)-C(14)-H(14B) 109.5

C(13)-C(14)-H(14C) 109.5

H(14A)-C(14)-H(14C) 109.5

H(14B)-C(14)-H(14C) 109.5

C(13)-C(15)-H(15A) 109.5

C(13)-C(15)-H(15B) 109.5

H(15A)-C(15)-H(15B) 109.5

C(13)-C(15)-H(15C) 109.5

H(15A)-C(15)-H(15C) 109.5

H(15B)-C(15)-H(15C) 109.5

C(13)-C(16)-H(16A) 109.5

C(13)-C(16)-H(16B) 109.5

H(16A)-C(16)-H(16B) 109.5

C(13)-C(16)-H(16C) 109.5

H(16A)-C(16)-H(16C) 109.5

H(16B)-C(16)-H(16C) 109.5

C(19)-C(17)-C(20) 105.7(4)

C(19)-C(17)-C(18) 106.4(3)

C(20)-C(17)-C(18) 108.6(3)

C(19)-C(17)-P(2) 112.7(3)

C(20)-C(17)-P(2) 107.5(3)

C(18)-C(17)-P(2) 115.5(3)

C(17)-C(18)-H(18A) 109.5

C(17)-C(18)-H(18B) 109.5

H(18A)-C(18)-H(18B) 109.5

C(17)-C(18)-H(18C) 109.5

H(18A)-C(18)-H(18C) 109.5

H(18B)-C(18)-H(18C) 109.5

C(17)-C(19)-H(19A) 109.5

C(17)-C(19)-H(19B) 109.5

H(19A)-C(19)-H(19B) 109.5

C(17)-C(19)-H(19C) 109.5

H(19A)-C(19)-H(19C) 109.5

H(19B)-C(19)-H(19C) 109.5

C(17)-C(20)-H(20A) 109.5

C(17)-C(20)-H(20B) 109.5

H(20A)-C(20)-H(20B) 109.5

C(17)-C(20)-H(20C) 109.5

H(20A)-C(20)-H(20C) 109.5

H(20B)-C(20)-H(20C) 109.5

C(23)-C(21)-C(24) 107.7(3)

C(23)-C(21)-C(22) 106.1(3)

C(24)-C(21)-C(22) 108.4(3)

C(23)-C(21)-P(2) 110.1(2)

C(24)-C(21)-P(2) 116.2(2)

C(22)-C(21)-P(2) 107.9(2)

C(21)-C(22)-H(22A) 109.5

C(21)-C(22)-H(22B) 109.5

H(22A)-C(22)-H(22B) 109.5

C(21)-C(22)-H(22C) 109.5

H(22A)-C(22)-H(22C) 109.5

H(22B)-C(22)-H(22C) 109.5

C(21)-C(23)-H(23A) 109.5

C(21)-C(23)-H(23B) 109.5

H(23A)-C(23)-H(23B) 109.5

C(21)-C(23)-H(23C) 109.5

H(23A)-C(23)-H(23C) 109.5

H(23B)-C(23)-H(23C) 109.5

C(21)-C(24)-H(24A) 109.5

C(21)-C(24)-H(24B) 109.5

H(24A)-C(24)-H(24B) 109.5

C(21)-C(24)-H(24C) 109.5

H(24A)-C(24)-H(24C) 109.5

H(24B)-C(24)-H(24C) 109.5

O(2)-C(25)-O(1) 123.7(3)

O(2)-C(25)-C(26) 120.3(4)

O(1)-C(25)-C(26) 116.1(3)

C(25)-C(26)-H(26A) 109.5

C(25)-C(26)-H(26B) 109.5

H(26A)-C(26)-H(26B) 109.5

C(25)-C(26)-H(26C) 109.5

H(26A)-C(26)-H(26C) 109.5

H(26B)-C(26)-H(26C) 109.5

C(25)-O(1)-Pd 128.4(2)

C(1)-P(1)-C(9) 111.36(19)

C(1)-P(1)-C(5) 112.35(16)

C(9)-P(1)-C(5) 111.03(16)

C(1)-P(1)-Pd 88.32(11)

C(9)-P(1)-Pd 107.29(11)

C(5)-P(1)-Pd 124.40(10)

C(13)-P(2)-C(21) 108.09(15)

C(13)-P(2)-C(17) 108.76(17)

C(21)-P(2)-C(17) 106.05(16)

C(13)-P(2)-Pd 107.88(10)

C(21)-P(2)-Pd 109.75(10)

C(17)-P(2)-Pd 116.07(11)

C(2)-Pd-O(1) 162.35(11)

C(2)-Pd-P(1) 68.31(9)

O(1)-Pd-P(1) 94.17(6)

C(2)-Pd-P(2) 99.87(9)

O(1)-Pd-P(2) 97.34(6)

P(1)-Pd-P(2) 167.01(3)

O(2B)-C(1A)-O(1B) 119.6(6)

O(2B)-C(1A)-C(2B) 141.7(6)

O(1B)-C(1A)-C(2B) 95.2(6)

O(1A)-C(1A)-O(2A) 105.0(6)

O(1A)-C(1A)-C(2A) 136.7(6)

O(2A)-C(1A)-C(2A) 117.0(5)

______

Anisotropic displacement parameters (Å2x 103) for palladacycle A. The anisotropic displacement factor exponent takes the form: -22[ h2a*2U11 + ... + 2 h k a* b* U12 ]

______

U11 U22 U33 U23 U13 U12

______

C(1) 70(2) 50(2) 45(2) 2(2) 3(2) 3(2)

C(2) 73(2) 41(2) 40(2) -2(1) 5(2) -4(2)

C(3) 70(2) 74(3) 64(2) 3(2) -16(2) -15(2)

C(4) 133(4) 76(3) 46(2) -5(2) 7(2) 17(3)

C(5) 50(2) 45(2) 47(2) 16(1) 5(1) 6(1)

C(6) 57(2) 56(2) 66(2) 11(2) 6(2) 20(2)

C(7) 90(3) 56(2) 77(3) 19(2) 11(2) -9(2)

C(8) 72(2) 78(3) 50(2) 29(2) 5(2) 12(2)

C(9) 36(2) 99(3) 60(2) 32(2) 15(2) 13(2)

C(10) 60(2) 114(4) 89(3) 48(3) 24(2) 44(2)

C(11) 56(2) 130(4) 73(3) 44(3) 34(2) 26(2)

C(12) 40(2) 138(5) 94(3) 36(3) -1(2) -9(2)

C(13) 29(2) 79(2) 49(2) 25(2) -1(1) -11(2)

C(14) 35(2) 102(3) 79(3) 34(2) 6(2) 10(2)

C(15) 36(2) 124(4) 67(2) 38(2) 13(2) -6(2)

C(16) 57(2) 128(4) 73(3) 21(3) -15(2) -47(2)

C(17) 77(2) 45(2) 57(2) 7(2) 7(2) 4(2)

C(18) 103(3) 55(2) 75(3) 25(2) 7(2) -5(2)

C(19) 176(5) 39(2) 74(3) 3(2) 4(3) 10(3) 84

C(20) 69(3) 67(3) 117(4) 18(3) 25(2) 28(2)

C(21) 41(2) 58(2) 35(2) 3(1) -5(1) -3(1)

C(22) 40(2) 66(2) 70(2) 3(2) -12(2) -9(2)

C(23) 70(2) 66(2) 45(2) -6(2) 6(2) 1(2)

C(24) 74(2) 84(3) 44(2) 16(2) -14(2) -4(2)

C(25) 67(2) 49(2) 40(2) 3(1) 12(2) 2(2)

C(26) 126(4) 45(2) 74(3) -16(2) 24(3) -5(2)

O(1) 57(1) 36(1) 52(1) -2(1) 3(1) -1(1)

O(2) 65(2) 100(2) 88(2) -3(2) 7(2) 19(2)

P(1) 35(1) 47(1) 36(1) 13(1) 8(1) 6(1)

P(2) 31(1) 42(1) 32(1) 7(1) 2(1) -4(1)

Pd 32(1) 31(1) 32(1) 3(1) 5(1) -1(1)

C(1A) 69(3) 74(3) 140(5) 43(3) -32(3) -25(2)

______

Calculated hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 103) for palladacycle A.

______

x y z U(eq)

______

H(2A) 8669 9610 9088 62

H(2B) 6790 9636 9156 62

H(3A) 10068 8778 9755 105

H(3B) 9759 8747 10729 105

H(3C) 10159 9329 10312 105

H(4A) 6094 9450 10657 128

H(4B) 7775 9731 10862 128

H(4C) 7368 9148 11274 128

H(6A) 9954 7989 9955 89

H(6B) 9254 7663 9148 89

H(6C) 9676 7334 9998 89

H(7A) 6583 7279 9105 111

H(7B) 5512 7338 9890 111

H(7C) 7036 6948 9950 111

H(8A) 8258 8106 11204 100

H(8B) 8040 7447 11218 100

H(8C) 6529 7843 11167 100

H(10A) 4436 9186 8793 130

H(10B) 4511 9382 9749 130

H(10C) 2922 9122 9334 130

H(11A) 4548 8643 10906 128

H(11B) 4325 8007 10642 128

H(11C) 2904 8436 10482 128

H(12A) 4204 8208 8424 136

H(12B) 2691 8172 8971 136

H(12C) 4107 7741 9129 136

H(14A) 10454 8653 7674 108

H(14B) 11944 8765 7131 108

H(14C) 10394 8483 6707 108

H(15A) 10252 9872 5884 113

H(15B) 10271 9235 5603 113

H(15C) 11821 9511 6037 113

H(16A) 10579 9634 8090 130

H(16B) 10553 10113 7398 130

H(16C) 12047 9711 7519 130

H(18A) 7524 10280 5762 116

H(18B) 8918 10500 6387 116

H(18C) 7263 10817 6324 116

H(19A) 7224 10156 8291 145

H(19B) 7058 10740 7818 145

H(19C) 8723 10430 7893 145

H(20A) 5015 9869 6403 125

H(20B) 4935 10440 6909 125

H(20C) 4951 9861 7400 125

H(22A) 4636 9109 6425 88

H(22B) 5358 8532 6757 88

H(22C) 4737 8594 5800 88

H(23A) 7941 8213 6325 91

H(23B) 8849 8550 5639 91

H(23C) 7215 8250 5383 91

H(24A) 6169 9676 5376 102

H(24B) 6155 9128 4812 102

H(24C) 7785 9430 5068 102

H(26A) 6819 7046 6669 121

H(26B) 5805 7064 7480 121

H(26C) 7454 6743 7511 121

______

Torsion angles [°] for palladacycle A.

______

C(3)-C(1)-C(2)-Pd 91.5(3)

C(4)-C(1)-C(2)-Pd -147.9(3)

P(1)-C(1)-C(2)-Pd -23.2(2)

O(2)-C(25)-O(1)-Pd -15.6(5)

C(26)-C(25)-O(1)-Pd 165.8(2)

C(3)-C(1)-P(1)-C(9) 162.7(2)

C(4)-C(1)-P(1)-C(9) 32.9(3)

C(2)-C(1)-P(1)-C(9) -87.8(2)

C(3)-C(1)-P(1)-C(5) 37.4(3)

C(4)-C(1)-P(1)-C(5) -92.4(3)

C(2)-C(1)-P(1)-C(5) 146.9(2)

C(3)-C(1)-P(1)-Pd -89.4(2)

C(4)-C(1)-P(1)-Pd 140.8(3)

C(2)-C(1)-P(1)-Pd 20.12(19)

C(11)-C(9)-P(1)-C(1) -78.1(4)

C(10)-C(9)-P(1)-C(1) 46.1(3)

C(12)-C(9)-P(1)-C(1) 160.4(3)

C(11)-C(9)-P(1)-C(5) 47.9(4)

C(10)-C(9)-P(1)-C(5) 172.1(3)

C(12)-C(9)-P(1)-C(5) -73.6(3)

C(11)-C(9)-P(1)-Pd -173.2(3)

C(10)-C(9)-P(1)-Pd -49.0(3)

C(12)-C(9)-P(1)-Pd 65.3(3)

C(7)-C(5)-P(1)-C(1) 173.3(2)

C(8)-C(5)-P(1)-C(1) 51.5(3)

C(6)-C(5)-P(1)-C(1) -69.4(3)

C(7)-C(5)-P(1)-C(9) 47.8(3)

C(8)-C(5)-P(1)-C(9) -74.0(3)

C(6)-C(5)-P(1)-C(9) 165.2(3)

C(7)-C(5)-P(1)-Pd -82.7(3)

C(8)-C(5)-P(1)-Pd 155.6(2)

C(6)-C(5)-P(1)-Pd 34.7(3)

C(15)-C(13)-P(2)-C(21) 44.8(3)

C(14)-C(13)-P(2)-C(21) -80.2(3)

C(16)-C(13)-P(2)-C(21) 165.7(2)

C(15)-C(13)-P(2)-C(17) -70.0(3)

C(14)-C(13)-P(2)-C(17) 165.0(3)

C(16)-C(13)-P(2)-C(17) 50.9(3)

C(15)-C(13)-P(2)-Pd 163.4(3)

C(14)-C(13)-P(2)-Pd 38.4(3)

C(16)-C(13)-P(2)-Pd -75.7(3)

C(23)-C(21)-P(2)-C(13) 44.9(3)

C(24)-C(21)-P(2)-C(13) -77.8(3)

C(22)-C(21)-P(2)-C(13) 160.3(2)

C(23)-C(21)-P(2)-C(17) 161.4(2)

C(24)-C(21)-P(2)-C(17) 38.7(3)

C(22)-C(21)-P(2)-C(17) -83.2(3)

C(23)-C(21)-P(2)-Pd -72.5(2)

C(24)-C(21)-P(2)-Pd 164.8(2)

C(22)-C(21)-P(2)-Pd 42.9(2)

C(19)-C(17)-P(2)-C(13) -76.1(3)

C(20)-C(17)-P(2)-C(13) 167.8(3)

C(18)-C(17)-P(2)-C(13) 46.4(3)

C(19)-C(17)-P(2)-C(21) 167.8(3)

C(20)-C(17)-P(2)-C(21) 51.8(3)

C(18)-C(17)-P(2)-C(21) -69.6(3)

C(19)-C(17)-P(2)-Pd 45.7(3)

C(20)-C(17)-P(2)-Pd -70.4(3)

C(18)-C(17)-P(2)-Pd 168.2(3)

C(1)-C(2)-Pd-O(1) 27.5(5)

C(1)-C(2)-Pd-P(1) 20.2(2)

C(1)-C(2)-Pd-P(2) -165.4(2)

C(25)-O(1)-Pd-C(2) -92.8(4)

C(25)-O(1)-Pd-P(1) -86.0(2)

C(25)-O(1)-Pd-P(2) 100.0(2)

C(1)-P(1)-Pd-C(2) -16.19(16)

C(9)-P(1)-Pd-C(2) 95.67(19)

C(5)-P(1)-Pd-C(2) -132.36(17)

C(1)-P(1)-Pd-O(1) 166.01(13)

C(9)-P(1)-Pd-O(1) -82.12(16)

C(5)-P(1)-Pd-O(1) 49.84(14)

C(1)-P(1)-Pd-P(2) -41.61(17)

C(9)-P(1)-Pd-P(2) 70.3(2)

C(5)-P(1)-Pd-P(2) -157.78(16)

C(13)-P(2)-Pd-C(2) 86.67(17)

C(21)-P(2)-Pd-C(2) -155.78(15)

C(17)-P(2)-Pd-C(2) -35.61(17)

C(13)-P(2)-Pd-O(1) -97.24(14)

C(21)-P(2)-Pd-O(1) 20.31(12)

C(17)-P(2)-Pd-O(1) 140.48(15)

C(13)-P(2)-Pd-P(1) 110.55(17)

C(21)-P(2)-Pd-P(1) -131.91(15)

C(17)-P(2)-Pd-P(1) -11.73(19)

______

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