DOCSLIB.ORG

Synthesis of Aromatic Aza-Metallapentalenes from 30

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthesis of Aromatic Aza-Metallapentalenes from 30 OPEN Synthesis of Aromatic SUBJECT AREAS: Aza-metallapentalenes from ORGANOMETALLIC CHEMISTRY Metallabenzene via Sequential Ring INORGANIC CHEMISTRY ORGANIC CHEMISTRY Contraction/Annulation THEORETICAL CHEMISTRY Tongdao Wang1, Feifei Han1, Haiping Huang1, Jinhua Li1, Hong Zhang1,2, Jun Zhu1, Zhenyang Lin2 & Haiping Xia1 Received 30 November 2014 1State Key Laboratory of Physical Chemistry of Solid Surfaces and Collaborative Innovation Center of Chemistry for Energy Materials Accepted (iChEM), and Department of Chemistry, Xiamen University, Xiamen 361005, China, 2Department of Chemistry, The Hong Kong 23 February 2015 University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. Published 9 April 2015 The concept of aromaticity has long played an important role in chemistry and continues to fascinate both experimentalists and theoreticians. Among the archetypal aromatic compounds, heteroaromatics are particularly attractive. Recently, substitution of a transition-metal fragment for a carbon atom in the anti-aromatic hydrocarbon pentalene has led to the new heteroaromatic osmapentalenes. However, Correspondence and construction of the aza-homolog of osmapentalenes cannot be accomplished by a similar synthetic requests for materials manipulation. Here, we report the synthesis of aza-osmapentalenes by sequential ring contraction/ should be addressed to annulation reactions of osmabenzenes via osmapentafulvenes. Nuclear magnetic resonance spectra, X-ray H.Z. ([email protected]); crystallographic analysis, and DFT calculations all suggest that these aza-osmapentalenes exhibit aromatic character. Thus, the stepwise transformation of metallabenzenes to metallapentafulvenes and then Z.L. ([email protected]) or aza-metallapentalenes provides an efficient and facile synthetic route to these bicyclic heteroaromatics. H.X. (hpxia@xmu. edu.cn) s one of the most fundamental chemistry concepts, aromaticity has been continually investigated since Faraday’s discovery of benzene in 18251 and Kekule´’s famous alternating single- and double-bond cyclic structure proposed in 18652,3. The Hu¨ckel aromaticity rule4 is applied to cyclic compounds containing 4n A 5–8 1 2p electrons, but Möbius topologies favour 4n delocalized p electron counts . In general, aromatic com- pounds are substantially more stable thermodynamically and anti-aromatic compounds less stable than appro- priate non-aromatic reference systems. Synergistic interplay of theoretical and experimental investigations has led to the synthesis and characterisation of numerous aromatic molecules with interesting structural features and properties9,10. The incorporation of heteroatoms or related groups into aromatic hydrocarbons can result in various heteroaromatic compounds. These introduced heteroatoms are not limited to main-group atoms or related groups; they also include transition-metal fragments. As a result of the increasing structural and com- positional variety of aromatic species, the definitions and criteria for characterising aromaticity have also been developing rapidly11. Metallaaromatics12–14 are organometallic species derived from the replacement of a (hydro)carbon unit in conventional aromatic hydrocarbons with a transition-metal fragment. As typical metallaaromatic compounds, metallabenzene complexes have been extensively studied by both experimentalists and theoreticians, dating back to the first computationally proposed metallabenzene complexes by Thorn and Hoffman15 in 1979. The increase in the variety of the metallaaromatic family is further evidenced by the recent discovery of metallapyridines16–18, which are azaheterocyclic analogues of metallabenzenes. Very recently, efforts to expand the aromatic family has also led to the discovery of the first metallapentalene (osmapentalene)19,20, which has been shown to exhibit aromaticity. Theoretical computations reveal that all these osmapentalenes with planar metallacycle benefit from Craig-Möbius aromaticity. The involvement of transition-metal d orbitals in the p conjugation switches the Hu¨ckel anti-aromaticity of pentalene into the Möbius aromaticity of metallapentalene. The introduction of nitrogen atoms into the pentalene system lead to the heterocyclic analogs of pentalene which are broadly defined as azapentalenes. Similar to the parent pentalenes, azapentalenes are anti-aromatic by virtue of a 8-p-electron system21. Some azapentalene molecules that contain nitrogen atoms in the bridgehead positions can be consid- SCIENTIFIC REPORTS | 5 : 9584 | DOI: 10.1038/srep09584 1 www.nature.com/scientificreports Figure 1 | The proposed structure of aza-metallapentalene. ered as analogs of a pentalene dianion, and these molecules are benzene 1-I was verified by X-ray diffraction analysis (Fig. 3b; the actually aromatic22. The isolation of the metallapentalene prompted relevant experimental details are presented in Supplementary us to investigate whether an aza-metallapentalene exists and, if so, Figures and Methods). Subsequent treatment of 1-I with aniline in how the synthesis could be achieved. As shown in Fig. 1, the structure the presence of sodium hexafluorophosphate afforded the expected of an aza-metallapentalene resembles that of pentalene, which is osmacyclopentadiene 2-PF6 in 95% yield (Fig. 3a). The complex 2- generally considered to be an anti-aromatic molecule, prompting PF6 was characterised by multinuclear nuclear magnetic resonance us to consider whether an aza-metallapentalene, which is structurally (NMR) spectroscopy, single-crystal X-ray diffraction analysis, and and electronically analogous to metallapentalene, is also aromatic. In high-resolution mass spectroscopy. The structure of 2-PF6 is shown this paper, we present the synthesis and characterisation of aza- in Fig. 3c. The X-ray diffraction analysis demonstrated that 2-PF6 metallapentalenes, which were obtained from metallabenzenes via contains a coplanar metallacyclopentadiene ring with an exocyclic sequential ring contraction/annulation reactions. imino group. The structural parameters indicated that the metalla- cycle of 2-PF6 could be represented by two resonance structures, 2- Results PF6 and 2b-PF6 (Fig. 3a), with 2-PF6 as the more dominant structure. Synthesis of the first aza-metallapentalene. The recently reported The structural data (averaged bond lengths) also indicated that both osmapentalene19,20 was synthesised (derived) from the protonation the metallacycles in 1-I and 2-PF6 have delocalised structures. In of osmapentalyne (Fig. 2a). Experimentally, osmapentalyne23 was addition, the six atoms Os1 and C1-C5 in each complex are approxi- mately coplanar, which is reflected by their small mean deviation observed to be thermally stable and easy to prepare via the ˚ ˚ reaction of osmium complexes with terminal alkynes (Fig. 2a). (0.0129 A for 1-I; 0.0331 A for 2-PF6) from the least-squares plane. Inspired by this observation, we initially attempted to react As shown in Fig. 3a, the resonance structure 2b-PF6 (metallapen- osmium complexes with a number of nitriles such as benzonitrile tafulvene) contributes to the overall structure of the complex 2-PF6. 27 or acetonitrile in the hope of obtaining the corresponding aza- Since pentafulvene molecules are normally considered aromatic, osmapentalynes. However, the expected reactions did not occur, we assume that the metallapentafulvene 2-PF6 is also aromatic, as only osmabenzenes or other osmacycles were detected, which have is indeed supported by our density functional theory (DFT) results been previously reported24,25. Therefore, the preparation of an aza- (vide infra). metallapentalene via the synthesis of an aza-osmapentalyne followed According to the retrosynthetic analysis shown in Fig. 2b, the by protonation is unfeasible. complex 2-PF6 could be used as the precursor to afford the desired Previously, we synthesised osmacyclopentadienes, each bearing an aza-metallapentalene by introducing an additional carbon atom. To ; exocyclic C 5 N bond, by reacting an osmabenzene complex with test this idea, reactions of 2-PF6 with the propynols RCH(OH)C amines26 (Fig. 2b). We envisioned that an aza-osmapentalene might CH in the presence of Ag2O were carried out in the hope of obtaining be directly obtained by introducing a new carbon atom, with the the desired aza-osmapentalene complexes. Triethylamine was used intention of inducing a further annulation reaction yielding an osma- in the reactions to ensure that an acetylide ligand could be easily cyclopentadiene monocyclic system, as illustrated by the retrosyn- delivered to the osmium metal centre (Warning: the reaction may thetic analysis shown in Fig. 2b. proceed through the formation of silver acetylide, which decomposes We first modified an osmabenzene complex by ligand substitution violently on contact with moisture and water producing highly flam- to generate the more stable osmabenzene 1-I. The structure of osma- mable and explosive acetylene gas, and causing fire and explosion Figure 2 | Previous work and initial attempt. (a) Protonation of osmapentalyne produces aromatic osmapentalene. (b) Reactions of osmabenzene with amines, leading to the formation of osmacyclopentadiene with an exocyclic C 5 N bond. SCIENTIFIC REPORTS | 5 : 9584 | DOI: 10.1038/srep09584 2 www.nature.com/scientificreports Figure 3 | Synthesis of osmacyclopentadiene 2-PF6. (a) The reaction of osmabenzene 1-I with aniline produces osmacyclopentadiene 2-PF6. (b, c) X-ray structures of 1-I (b) and 2-PF6 (c) (50% probability level). Phenyl moieties in PPh3, the counter
Load more

Recommended publications
  • Electrooxidation Enables Highly Regioselective Dearomative Annulation of Indole and Benzofuran Derivatives
    ARTICLE https://doi.org/10.1038/s41467-019-13829-4 OPEN Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives Kun Liu1, Wenxu Song1, Yuqi Deng1, Huiyue Yang1, Chunlan Song1, Takfaoui Abdelilah1, Shengchun Wang 1, Hengjiang Cong 1, Shan Tang1 & Aiwen Lei1* 1234567890():,; The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functio- nalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate- determining step. 1 College of Chemistry and Molecular Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, P. R. China. *email: aiwenlei@whu. edu.cn NATURE COMMUNICATIONS | (2020) 11:3 | https://doi.org/10.1038/s41467-019-13829-4 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13829-4 reaking the aromatic systems of electron-rich arenes or fused indolines (Fig. 1a)39–44. Therefore, it is highly appealing to heteroarenes provides three-dimensional chemicals of high develop efficient approaches to allow for their preparation.
    [Show full text]
  • Robert Burns Woodward
    The Life and Achievements of Robert Burns Woodward Long Literature Seminar July 13, 2009 Erika A. Crane “The structure known, but not yet accessible by synthesis, is to the chemist what the unclimbed mountain, the uncharted sea, the untilled field, the unreached planet, are to other men. The achievement of the objective in itself cannot but thrill all chemists, who even before they know the details of the journey can apprehend from their own experience the joys and elations, the disappointments and false hopes, the obstacles overcome, the frustrations subdued, which they experienced who traversed a road to the goal. The unique challenge which chemical synthesis provides for the creative imagination and the skilled hand ensures that it will endure as long as men write books, paint pictures, and fashion things which are beautiful, or practical, or both.” “Art and Science in the Synthesis of Organic Compounds: Retrospect and Prospect,” in Pointers and Pathways in Research (Bombay:CIBA of India, 1963). Robert Burns Woodward • Graduated from MIT with his Ph.D. in chemistry at the age of 20 Woodward taught by example and captivated • A tenured professor at Harvard by the age of 29 the young... “Woodward largely taught principles and values. He showed us by • Published 196 papers before his death at age example and precept that if anything is worth 62 doing, it should be done intelligently, intensely • Received 24 honorary degrees and passionately.” • Received 26 medals & awards including the -Daniel Kemp National Medal of Science in 1964, the Nobel Prize in 1965, and he was one of the first recipients of the Arthur C.
    [Show full text]
  • Annulation of Propargylic Dithioacetals Leading to Furan-Containing Oligoaryls*
    Pure Appl. Chem., Vol. 77, No. 7, pp. 1213–1219, 2005. DOI: 10.1351/pac200577071213 © 2005 IUPAC Annulation of propargylic dithioacetals leading to furan-containing oligoaryls* Tien-Yau Luh Department of Chemistry, National Taiwan University, Taipei 106, Taiwan Abstract: Reaction of propargylic dithioacetals with BuLi followed by treatment with di- aldehydes yields the corresponding allenyl carbinols which can be cyclized to give the 2,3,5-trisubstituted furans. The use of this strategy for the synthesis of a range of alternating benzene-furan oligoaryls is described. Keywords: annulation; propargylic dithioacetals; oligoaryls; furans; optoelectronic applica- tions; cyclophanes; convergent synthesis. INTRODUCTION Direct conversion of carbon–sulfur bonds in dithioacetal functionality into the corresponding car- bon–carbon bonds has been extensively studied in recent years [1]. Representative examples are shown in Scheme 1. The substituents R1 and/or R2 can be aryl, alkenyl alkynyl, or, more recently, alkyl groups. Since carbon and sulfur atoms have similar electronegativities, the polarity of the carbon–sulfur bond can vary depending on the nature of the substrates and reaction conditions. In general, the carbon end of a carbon–sulfur bond can serve as a carbocationic equivalent to reaction with a nucleophile. Alternatively, the nucleophile can attack at the sulfur end of a carbon–sulfur bond to generate the car- banion, which can then react with an electrophile leading to the corresponding substitution product. In this case, the carbanionic moiety must be stabilized by a neighboring stabilizing substituent(s). Ikehira and Krief have shown that benzylic dithiolanes react with butyllithium followed by protonolysis to give the corresponding mono-desulfurized products (eq.
    [Show full text]
  • Π-Conjugated Carbocycles and Heterocycles Via Annulation Through C-H and X-Y Activation Across CC Triple Bonds
    Issue in Honor of Dr. Jhillu S. Yadav ARKIVOC 2016 (ii) 9-41 π-Conjugated carbocycles and heterocycles via annulation through C-H and X-Y activation across CC triple bonds Yoshinori Yamamoto,a,b Abdulrahman I. Almansour,c Natarajan Arumugam,c and Raju Suresh Kumar c a WPI-AIMR, Tohoku University, Sendai 980-8577, Japan b State Key Lab of Fine Chemicals, Dalian University of Technology, Dalian 116 023, China c Department of Chemistry, College of Science, King Saud University, P.O.Box 2455, Riyadh 11451, Saudi Arabia E-mail: [email protected], [email protected] This account is dedicated to Professor J. S. Yadav, in honor of his distinguished career in synthetic organic chemistry, and of his 65th birthday DOI: http://dx.doi.org/10.3998/ark.5550190.p009.282 Abstract In this account our own research results on the methods of annulation and hetero-annulation across alkynes are summarized, especially emphasizing the annulation and hetero-annulation through C-H and X-Y activation. A wide range of quinolines, isoquinolines, indoles, benzofurans, indenes, and benzothiophenes can be synthesized via mono-annulation of ortho-alkynylaryl derivatives using transition metal catalysts and/or iodine reagents. Benzocarbazoles, benzonaphthothiophenes, and indenochromenes can be synthesized via cascade annulation of 1,2-dialkynyl substituted benzene derivatives. Palladium-catalyzed crossover annulation of compounds bearing two vicinal CC triple bonds attached to an unsaturated ring gives dibenzopentalenes through C-H activation, and intramolecular cross annulation of bis- biarylalkynes affords 9,9-bifluorenylidenes via dual C-H activation. Keywords: Optoelectronic materials, quinolines, isoquinolines, indoles, benzofurans, indenes, benzothiophenes, C-H activation, palladium catalysis, gold catalysis Table of Contents 1.
    [Show full text]
  • Combining Furan Annulation, Heck Reaction, and Sonogashira Coupling
    ORGANIC LETTERS 2002 Combining Furan Annulation, Heck Vol. 4, No. 24 Reaction, and Sonogashira Coupling for 4305-4307 the Synthesis of Oligoaryls Ching-Yuan Liu† and Tien-Yau Luh*,†,‡ Department of Chemistry, National Taiwan UniVersity, Taipei, Taiwan 106, and Institute of Chemistry, Academia Sinica, Taipei, Taiwan 115 [email protected] Received September 21, 2002 ABSTRACT A variety of benzene−furan−alkene/alkyne conjugated oligomers of precise length and constitution were synthesized iteratively by combining furan annulation, Heck reaction, and Sonogashira coupling. Oligoaryls and their vinylene or acetylene homologues of hole-transporting material in electroluminescent devices.7 The desired conjugation length have been widely investigated basic synthetic strategy shown in eq 1 involves the reaction because of their potential optoelectronic applications.1 There of a thiolato-substituted allenyl anion 3, generated in situ has been extensive uses of heteroaromatic rings such as from 1 and BuLi, with a dialdehyde followed by the acid- thiophene in these applications.1 Interestingly, studies on catalyzed ring closure. Since both vinyl and alkynyl sub- furan derivatives for these applications have been rare.2-5 stituents are stable under the reaction conditions,6 it is We recently reported a convenient one-pot synthesis of envisaged that substrates containing such functionalities can 8 9 Publication Date (Web): November 5, 2002 | doi: 10.1021/ol026941t symmetric oligoaryls 2 containing two furan moieties (eq undergo Heck and Sonogashira reactions, respectively, to 1).6,7 These oligoaryls are thermally stable and exhibit bright extend the chain length while incorporating the aldehyde fluorescence in the blue light region. It is noteworthy that functionality at both ends of the oligoaryl chain.
    [Show full text]
  • Fischer Indole Synthesis Applied to the Total Synthesis of Natural Products Cite This: RSC Adv.,2017,7,52852 Majid M
    RSC Advances REVIEW View Article Online View Journal | View Issue Fischer indole synthesis applied to the total synthesis of natural products Cite this: RSC Adv.,2017,7,52852 Majid M. Heravi, * Sahar Rohani, Vahideh Zadsirjan* and Nazli Zahedi One of the oldest and most useful reactions in organic chemistry is the Fischer indole synthesis (FIS). It is known to have a wide variety of applications including the synthesis of indole rings, often present as the Received 27th September 2017 framework in the total synthesis of natural products, particularly those found in the realm of alkaloids, Accepted 3rd November 2017 which comprise a ring system known as an indole alkaloid. In this review, we are trying to emphasize the DOI: 10.1039/c7ra10716a applications of FIS as an old reaction, which is currently applied to the total synthesis of biologically rsc.li/rsc-advances active natural products and some other complex targets. 1. Introduction prescribed drugs or medications.1 Remarkably, the name indole is a combination of the words indigo and oleum because Creative Commons Attribution 3.0 Unported Licence. Nowadays, there has been increasing attention on the total initially, indole was prepared and identied from the reaction synthesis of bioactive natural products and their synthetic of the indigo dye with oleum.2 As a matter of fact, one of the analogues in the arena of organic chemistry. Novel synthetic most plentiful heterocyclic systems found in nature is indole. It approaches and strategies are available that permit formation is a vital functional nucleus in the structures of different dyes, of novel complex molecules or already structurally known fragrances, pharmaceuticals and agricultural chemicals.3,4 naturally occurring compounds which can be used as Indole ring moieties became important structural components in diverse natural pharmaceutical agents, hence their synthesis and functionalization is a key eld in heterocyclic chemistry, Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran.
    [Show full text]
  • A De Novo Peroxidase Is Also a Promiscuous Yet Stereoselective Carbene Transferase
    bioRxiv preprint doi: https://doi.org/10.1101/328484; this version posted November 1, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A de novo peroxidase is also a promiscuous yet stereoselective carbene transferase Stenner, Richard1,2; Steventon, Jack W.1,3; Seddon, Annela2,4; Anderson, J. L. Ross1,3*. 1School of Biochemistry, University of Bristol, University Walk, Bristol, BS8 1TD, UK. 2Bristol Centre for Functional Nanomaterials, HH Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, BS8 1TL, UK. 3BrisSynBio Synthetic Biology Research Centre, Life Sciences Building, University of Bristol, Tyndall Avenue, Bristol BS8 1TQ, UK. 4School of Physics, HH Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, BS8 1TL, UK. email: [email protected] By constructing an in vivo assembled, catalytically proficient peroxidase, C45, we have recently demonstrated the catalytic potential of simple, de novo-designed heme proteins. Here we show that C45’s enzymatic activity extends to the efficient and stereoselective intermolecular transfer of carbenes to olefins, heterocycles, aldehydes and amines. Not only is this the first report of carbene transferase activity in a completely de novo protein, but also of enzyme-catalyzed ring expansion of aromatic heterocycles via carbene transfer by any enzyme. Despite the significant advances in protein design, there still remain few examples of de novo enzymes that both approach the catalytic efficiencies of their natural counterparts and are of potential use in an industrial or biological context1-7.
    [Show full text]
  • Advances in the Asymmetric Total Synthesis of Natural Products Using Chiral Secondary Amine Catalyzed Reactions of Α,Β-Unsaturated Aldehydes
    molecules Review Advances in the Asymmetric Total Synthesis of Natural Products Using Chiral Secondary Amine Catalyzed Reactions of α,β-Unsaturated Aldehydes Zhonglei Wang 1,2 1 School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; [email protected] 2 School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China Academic Editor: Ari Koskinen Received: 12 August 2019; Accepted: 19 September 2019; Published: 19 September 2019 Abstract: Chirality is one of the most important attributes for its presence in a vast majority of bioactive natural products and pharmaceuticals. Asymmetric organocatalysis methods have emerged as a powerful methodology for the construction of highly enantioenriched structural skeletons of the target molecules. Due to their extensive application of organocatalysis in the total synthesis of bioactive molecules and some of them have been used in the industrial synthesis of drugs have attracted increasing interests from chemists. Among the chiral organocatalysts, chiral secondary amines (MacMillan’s catalyst and Jorgensen’s catalyst) have been especially considered attractive strategies because of their impressive efficiency. Herein, we outline advances in the asymmetric total synthesis of natural products and relevant drugs by using the strategy of chiral secondary amine catalyzed reactions of α,β-unsaturated aldehydes in the last eighteen years. Keywords: bioactive natural products; pharmaceuticals; asymmetric total synthesis; chiral secondary amines; α,β-unsaturated aldehydes 1. Introduction In 2000, the MacMillan group [1] first described the fundamental concept of LUMO-lowering iminium-ion activation. In 2005, the Jørgensen group [2,3] reported diarylprolinol silyl ether catalysts, which have also been used in iminium-ion catalysis.
    [Show full text]
  • And Trisubstituted Azulenes Using a Danheiser Annulation As the Key Step: an Advanced Organic Laboratory Experiment Rebecca M
    Masthead Logo Smith ScholarWorks Chemistry: Faculty Publications Chemistry 10-15-2012 Synthesis of Di- and Trisubstituted Azulenes Using a Danheiser Annulation as the Key Step: An Advanced Organic Laboratory Experiment Rebecca M. Thomas Kevin M. Shea Smith College, [email protected] Follow this and additional works at: https://scholarworks.smith.edu/chm_facpubs Part of the Chemistry Commons Recommended Citation Thomas, Rebecca M. and Shea, Kevin M., "Synthesis of Di- and Trisubstituted Azulenes Using a Danheiser Annulation as the Key Step: An Advanced Organic Laboratory Experiment" (2012). Chemistry: Faculty Publications, Smith College, Northampton, MA. https://scholarworks.smith.edu/chm_facpubs/13 This Article has been accepted for inclusion in Chemistry: Faculty Publications by an authorized administrator of Smith ScholarWorks. For more information, please contact [email protected] Synthesis of Di- and Trisubstituted Azulenes Using a Danheiser Annulation as the Key Step: An Advanced Organic Laboratory Experiment Rebecca M. Thomas and Kevin M. Shea* Department of Chemistry, Smith College, Northampton, Massachusetts 01063, United States ABSTRACT: This three-week experiment provides students with an inquiry-based approach focused on learning traditional skills like primary literature interpretation, reaction design, flash column chromatography, and NMR analysis. Additionally, students address higher order concepts like the origin of azulene’s blue color, the mechanism of the Danheiser annulation (step 1), identification of an unknown
    [Show full text]
  • Diazo-Mediated Metal Carbenoid Chemistry ~Recent Developments of Variety Bond Formation Methods~
    Literature Seminar (D2 Part) 2011/04/06 (Wed) Noriaki Takasu (D2) Diazo-mediated Metal Carbenoid Chemistry ~Recent Developments of Variety Bond Formation Methods~ Cyclopropanation C-H Insertion [4+3] Cyclization R1 R2 N2 R1 LnM 2 LnM R [3+2] Cyclization Metal Carbenoid Ylide Formation Coupling N-H, O-H Insertion Recently, many metal catalyzed C-H activation reactions have been reported, but many reactions have not become reaction using wide range (selectivity, functional group tolerance). The metal-carbenoid intermediates are capable of undergoing a range of unconventional reactions, and due to their high energy, they are ideal for initiating cascade sequences leading to the rapid generation of structural complexity. These species are using for many type C-H activated reactions, C-C or C-heteroatom bond formations, and skeletal constructions. In this seminar, I talk about many type metal-carbenoid reactions from various metal. Contents 1. Carbenoid (P.1-2) 2. Rhodium Carbenoid Induced Reaction (P.3-10) 3. Copper Carbenoid Induced Reaction (P.11-12) 4. Palladium Carbenoid Induced Reaction (P.13-14) 5. Other Metal Carbenoid Induced Reaction (P.15-16) 6. Summary & Perspective (P.17) 1. Carbenoid 1-1. Carbene Carbene is a molecule containing a neutral carbon with a 2 valences R NN R R and 2 unshared electrons. C Carbenes are classified as either singlets or triprets depending upon their NHC R' electronic structure. Most carbenes are very short lived, although persistent carbenes are ref.) Nojiri's Lit known (example of stable carbene: N-Heterocyclic carbene; NHC). (M1 Part) p p R R Singlet Triplet R' R' • unshared electron pair ( orbital) and empty p orbital • 2 electron was shared with p orbital and orbital • resembles carbocation and carboanion united on same • resembles biradical carbon, so have nucleophilicity and electrophilicity • Typical angle (calculated) : 130~150° (reactivity depends on substituted groups).
    [Show full text]
  • Towards a Metal-Catalyzed Annulation Route to Pyridines
    Towards a Metal-Catalyzed Annulation Route to Pyridines and N-Hydroxy Pyrroles by Kenneth Matthew Whitmore A Thesis Submitted to the Faculty of Graduate and Postdoctoral Studies in Partial Fulfillment of the Requirements for the Master’s Degree in Chemistry Candidate Kenneth Matthew Whitmore Supervisor Dr. André M Beauchemin Ottawa-Carleton Chemistry Institute Faculty of Science University of Ottawa “© Kenneth Matthew Whitmore, Ottawa, Canada, 2012” i Abstract Despite progress in the metal-catalyzed synthesis of aromatic heterocycles, annulation routes towards 6-membered heterocycles remain underdeveloped. Specifically, routes towards pyridines are rare in spite of the prevalence of this moiety in novel drug candidates. Our initial efforts towards pyridines featured oximes as competent nucleophiles in the intramolecular, 6-exo dig annulation of alkynes using Brønsted acid catalysis. Two of the oxidation states required for subsequent aromatization are contained within the oxime via loss of water. An extension of this chemistry is presented and discussed, and involves the intramolecular metal- catalyzed 6-endo dig annulation of analagous alkynyl-oximes. Additionally, the discovery of a 5-exo dig annulation of related systems is discussed. ii “What I hear, I forget. What I see, I remember. What I do, I understand.” -Confucius iii Acknowledgements Firstly, I would like to thank Dr. André Beauchemin for initially taking me on as a Master’s student back in the Fall of 2009. André has been a constant source of support for the past two years, and has always shown enthusiasm about the results of my project. I know I have learned a lot from him both intellectually and personally, and I am eternally grateful to him for everything he has done for me.
    [Show full text]
  • Structure and Stability of the Heteroannulated [8–10]Circulenes: a Quantum-Chemical Study*
    Pure Appl. Chem., Vol. 82, No. 4, pp. 1011–1024, 2010. doi:10.1351/PAC-CON-09-10-36 © 2010 IUPAC, Publication date (Web): 19 March 2010 Structure and stability of the heteroannulated [8–10]circulenes: A quantum-chemical study* Tatyana N. Gribanova1, Nikolay S. Zefirov2, and Vladimir I. Minkin1,‡ 1Institute of Physical and Organic Chemistry at Southern Federal University, pr. Stachki 194/2, Rostov-on-Don, 344090, Russian Federation; 2Moscow State University, Leninskiye Gory, Moscow, 119899, Russian Federation Abstract: The structure and stability of a new family of heterocyclic [n]circulenes CnNnYn (n = 8–10; Y = N, P, As, BF2, AlF2, GaF2) have been computationally studied using density functional theory (DFT) B3LYP/6-311G* calculations. The geometry of the compounds is determined by the balance of steric factors and effects of aromatic π-electron delocalization depending on the electronegativity of heteroatoms. An increase in the bulkiness of peripheral atoms Y and enlargement of the inner Cn cycle leads to the gradual transformation of the bowl-shaped circulene structure (Y = N, BF2) to planar and then saddle-shaped forms (Y = P, As, AlF2, GaF2). The calculations performed manifest stabilization of the hetero annulated circulenes ensured by the strong aromatic character of the conjugated five-membered rings fringing the central non-aromatic or antiaromatic [8–10] annulene rings. Keywords: annulation; aromaticity; [n]circulenes; quantum-chemical calculations. INTRODUCTION The concept of aromaticity continues to be a topic of many studies concerned with its quantification and classification of the structural types of the relevant compounds [1–3]. In general, a (4n + 2) π-electronic ring framework serves as a reliable indicator of the aromatic character of a molecule or an ion.
    [Show full text]