The Free Internet Journal Review for Organic Chemistry Archive for Arkivoc 2017, part i, 257-355 Organic Chemistry Synthesis and properties of heteroaromatic carbenes of the imidazole and triazole series and their fused analogues Nikolai І. Korotkikh,a* Аlan H. Cowley,b Jason A.C. Clyburne,c Katherine N. Robertson,c Vagiz Sh. Saberov,a Nataliya V. Glinyanaya,d Gennady F. Rayenko,d and Оles P. Shvaikad a The Institute of Organic Chemistry, Ukrainian Academy of Sciences, 5, Murmanskaya Str., Kiev-94 02660, Ukraine b Department of Chemistry, The University of Texas at Austin, 1 University Station A5300, Austin, Texas 78712-0165, USA c The Atlantic Centre for Green Chemistry, Department of Chemistry, Saint Mary’s University, Halifax, Nova Scotia B3H 3C3, Сanada d The L.M. Litvinenko Institute of Physical Organic and Coal Chemistry, Ukrainian Academy of Sciences, 50 Kharkiv road, Kiev 02160, Ukraine E-mail: [email protected] Received 03-24-2017 Accepted 06-05-2017 Published on line 07-26-2017 Abstract The present review deals with the syntheses and properties of individual heteroaromatic carbenes of the imidazole, 1,2,4- and 1,2,3-triazole series, their fused analogs and mesoionic carbenes including unprecedented structures such as hyperbasic and hypernucleophilic carbenes. Particular emphasis is placed on their physical properties, novel chemical transformations, and catalytic properties. Keywords. Heteroaromatic carbenes, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles. DOI: https://doi.org/10.24820/ark.5550190.p010.110 Page 257 ©ARKAT USA, Inc Arkivoc 2017, i, 257-355 Korotkikh, N. I. et al. Table of Contents 1. Introduction 2. Synthesis of Carbenes of the Imidazole and Triazole Series and their Fused Analogues 2.1 Imidazol-2-ylidenes 2.1.1 Monoimidazol-2-ylidenes 2.1.2 Bis- and tris-imidazol-2-ylidenes 2.2 Fused aromatic analogues of imidazol-2-ylidenes 2.2.1 Fused monoimidazol-2-ylidenes 2.2.2 Bis-, tris- and poly-benzimidazol-2-ylidenes 2.3 1,2,4-Triazol-5-ylidenes 2.4 Hyperbasic and hypernucleophilic anionic carbenes 2.5 Mesoionic carbenes 2.5.1 Imidazolium-4(5)-ides 2.5.2 1,2,3-Triazolium-5-ides 3. Physical Properties of Stable Carbenes 3.1 1Н and 13С NMR spectra 3.2 Structures 3.3 Basicities and electron donating properties 3.4 Hyperbasic and hypernucleophilic carbenes (HBNC) 3.5 Steric properties 4. Transformations of Individual Carbenes 4.1 Rearrangements and autotransformations 4.1.1 Migrations of atoms and groups in stable carbenes 4.1.2 Other autotransformations 4.1.3 Ring expansions of heterocyclic carbenes 4.1.4 Dimerization reactions and cross-couplings 4.2 Х-Н Insertion Reactions 4.2.1 Insertions into polar Х-Н bonds 4.2.2 Hydrogen bonds of carbenes 4.2.3 Insertions into C-Н bonds 4.2.4 Carbenoid properties of carbene insertion products 4.3 Alkylation and Arylation of Carbenes 4.4 Reactions with Activated Multiple Bonds 4.4.1 Reactions with olefins 4.4.2 Reactions with acetylenes 4.4.3 Reactions with allenes and fullerenes 4.4.4 Reactions with СХ2 (X = O, S) 4.4.5 Reactions with azides 4.4.6 Reactions with diazoalkanes 4.4.7 Reactions with N2O and NO 4.4.8 Reactions with carbodiimides 4.5 Carbenes in the Synthesis of Zwitterionic and Ionic compounds 4.5.1 Reactions with esters Page 258 ©ARKAT USA, Inc Arkivoc 2017, i, 257-355 Korotkikh, N. I. et al. 4.5.2 Formation of zwitterionic compounds in reactions with multiple bonds and cyclic sulfoesters 4.6 Reactions with Non-metals and some Nucleophiles 5. Catalytic Properties of Carbenes and their Complexes with Transition Metals 5.1 Catalysis by carbenes 5.1.1 Transesterification reaction 5.1.2 Benzoin condensation 5.2 Catalysis by carbene complexes of transition metals 5.2.1 Reduction of multiple bonds with alcohols (hydrogen transfer) 5.2.2 Hydrodehalogenation reactions of haloarenes 6. Biological Activity of Carbene Derivatives 7. Conclusions References 1. Introduction A quarter of a century has elapsed since Bertrand and Arduengo discovered and then synthesized the first disubstituted derivatives of stable carbenes.1-5 In turn, this provided a strong impetus for increased research activity in the field. Particular emphasis was placed on the synthesis of carbenes and their derivatives, and studies of their structures, transformations, biological and catalytic properties proliferated. Prior to these results only inorganic and monosubstituted organic analogues of carbenes were known (carbon(II) monoxide CO, carbon(II) thioxide CS and isocyanides, RNC). Although not normally identified as carbenes, these compounds had long been used as ligands and reagents for organic synthesis. The preparation of other types of individual carbenes took longer to materialise.6,7 However, today a large number of compounds have been isolated; these are predominantly heterocyclic species and include heteroaromatic carbenes, phosphanyl- silylcarbenes, aminoalkyl- and diamino-carbenes of cyclic and acyclic series, borazino- and borazolo-carbenes, etc.8-20 One of the major focuses of carbene applications has been the catalysis of organic reactions.21-30 The connection between individual carbene structure and function has been reported in many publications. However, there remains a considerable problem in that the leading structures in any particular area have not yet been well identified. Overall, heteroaromatic carbenes of the imidazole, triazole (the 1,2,4- and more recently the 1,2,3-type) and benzimidazole series are the best known in this field. It is worth noting that in the literature the synthesis of carbene derivatives is often described (e.g., the number of metal carbene complexes is growing very rapidly) without the actual isolation of the individual precursor carbenes (their number is much less). The differences in properties between the two can be very significant. Although in situ transformations are sometimes able to do surprising things (see, for example, the recently described31 formation of carbene complexes of copper(I) from azolium salts and metallic copper), individual carbenes not only catalyse organic reactions but also open up new possibilities for organic synthesis.32,33 The present article is concerned with the syntheses, structural studies and transformations of individual heterocyclic carbenes of the іmіdazole and triazole series, as well as their fused analogues. The catalytic activities of these carbenes, and their derivatives, in some typical organic reactions (transesterifіcation and benzoin condensation) will be discussed, as will carbene complexes of transition metals (haloarene hydrodehalogenation and reduction of multiple bonds). These reactions can be used to study the influence of Page 259 ©ARKAT USA, Inc Arkivoc 2017, i, 257-355 Korotkikh, N. I. et al. catalyst structure on catalytic efficiency. During the discussion of such transformations, attention will be concentrated on structural rearrangements, and reactions with carbon and nitrogen electrophiles, particularly those with multiple bonds or nonmetals. The formation of complex compounds with metals and elemento- electrophiles of the main groups of the periodic table constitutes a very broad area, one that has been described in many reviews (see, for example, the most general of them34-37). Therefore, except in those cases where elementoderivatives are used for the synthesis of new types of carbenes or reactions of their ring expansions, the results of these studies are not considered in the present work. Attention has been paid to appropriate methods for the synthesis of carbene precursors (precarbenes), the carbenoid structures of which sometimes allow the achievement of in situ reactions. The results of such reactions are often comparable to those of free carbenes.7 Structures are numbered in this review according to the Scheme in which they first appear, in order to avoid a cumbersome sequence running into the 500s. We hope that this will be found convenient. 2. Synthesis of Carbenes of the Imidazole and Triazole Series and their Fused Analogues 2.1. Imidazol-2-ylidenes 2.1.1. Monoimidazol-2-ylidenes. Current methods for the preparation of іmіdazol-2-ylіdenes involve the deprotonation of meso-unsubstituted іmіdazolіum salts under the action of anhydrous and unprotic bases (metal hydrides, alkoxides, hexamethyldisilazanides, diisopropylamides, etc.). Using this approach Wanzlick et al.7 generated carbenes of the heterocyclic series in situ. However, Arduengo et al. provided the first example of a stable crystalline carbene 1,3-dі-(1-adamantyl)іmіdazol-2-ylidene 1D2 (R = 1-Ad) (Scheme 1).4 They demonstrated that the method is suitable for the isolation of individual substances and confirmed the lability of carbenes under environmental conditions (to water, oxygen and carbon dіoxide). Subsequently, 1,3- disubstituted imidazol-2-ylidenes,5,38-40 4,5-dihydroimidazol-2-ylidenes41 and acyclic diaminocarbenes42 were prepared and shown to behave in a similar fashion to the first Arduengo compound. In the latter case, there is a significant complexation of alkali metal cations, especially lithium, by the carbene. The precursors of іmіdazol-2-ylіdenes are 1,3-disubstituted іmіdazolіum salts that are obtained by the alkylation of relevant іmіdazoles. However, this approach is not suitable for the preparation of sterically shielded 1,3-dіalkylimidazolium salts such as 1C. As a consequence, a process that combines amines with formaldehyde (or paraformaldehyde), followed by the reaction of glyoxal with the condensation product 1B in the presence of acids, was devised (Scheme 1).43,44 Tetraphenylimidazolium salt 1E1 and 1,3-di(1-adamantyl)- 4,5-diphenylimidazolium salt 1E2 were obtained in other pathways: via the oxidation of the corresponding thione with nitric acid40 and via the quaternization of 4,5-diphenylimidazole with 1-bromoadamantane in the presence of sodium acetate in acetic acid,45 respectively. Scheme 1. Arduengo’s method for the preparation of imidazol-2-ylidenes via diaminomethanes. Page 260 ©ARKAT USA, Inc Arkivoc 2017, i, 257-355 Korotkikh, N. I. et al.