N-heterocyclic carbene catalyzed reactions of α,β-unsaturated aldehydes and a variety of electrophiles allow the facile preparation of a diverse array of annulation products including trisubstituted cyclopentenes, γ-lactams, and bicyclic β-lactams. The substrate scope of these reactions, however, is limited by the difficulties of preparing the startingα,β-unsaturated aldehydes. We now report that α′-hydroxyenones, which can be prepared in a single convenient step from aromatic and heteroaromatic aldehydes, can serve as efficient surrogates for enals in the annulation reactions. This protocol allows the facile preparation and use of substrates bearing nitrogen heterocycles. These reagents have also allowed us to demonstrate that, in contrast to other classes of aldehydes, the formation of the Breslow intermediate from enals and N-heterocyclic carbenes is irreversible under the reaction conditions.

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Abstractα′-Hydroxyenones undergo clean, catalytic amidations with amines promoted by the combination of an N-heterocyclic carbene and 1,2,4-triazole.The ubiquity of amide-containing organic compounds coupled with the generally expensive and wasteful methods for their formation have engendered intense, recent efforts in the identification and development of catalytic methods for amide-bond formation. 1 The most attractive approach, the direct catalytic coupling of carboxylic acids and amines, 2 can be achieved with certain boronic acids as catalysts under conditions involving high temperatures2a,b or the use of molecular sieves. 2c Elegant work with transition metal catalysts has made possible the formation of amides from amines and alcohols, with the formation of H 2 as the only stoichiometric byproduct. 3 Chemoselective, reagentless amide-formations, are an exciting area for the synthesis of peptides and biomolecules, 4 but the need for specialized starting materials limits the utility of these processes for the synthesis of simple amides. 5 In seeking to develop simple, waste-free methods for the synthesis of carboxylic acid derivatives, we have advanced the concept of redox esterifications and amidations. 6 These reactions, promoted by N-heterocyclic carbenes, 7 proceed via transient activated carboxylates catalytically generated by internal redox reactions of α-functionalized aldehydes including epoxyaldehydes, 8 α-haloaldehydes, 9 formyl cyclopropanes, 10 and α,β-unsaturated aldehydes. 11 Such esterifications proceed smoothly in high yield without stoichiometric amounts of reagents or byproducts. The amidations, however, are often complicated by competing imine formation and proceed only in the presence of a suitable additive such as imidazole or HOAt. 12 Thus, while feasible, this redox amidation requires further refinement to improve the yields, catalyst loadings, and scope to impact the need for simple amidation reactions. In this communication, we report such an advance in the form of catalytic amidations of α′-hydroxyenones in the presence of a triazolium precatalyst and 1,2,4-triazole as a co-catalyst.The use of α′-hydroxyenones as substrates for NHC-catalyzed reactions stems from our recent studies on their use as surrogates for α,β-unsaturated aldehydes. 13 These starting materials are attractive due to their facile, one-step preparation from widely available starting materials, 14 their stability towards long-term storage, and their tendancy to be crystalline products. In contrast, the corresponding α,β-unsaturated aldehydes often require multi-step syntheses employing expensive and wasteful reagents. 15 We also recognized that the use of α′- NIH Public Access Author ManuscriptChem Commun (Camb) We were pleased to see that esterifications from alcohols and the α′-hydroxyenones proceeded smoothly, but initial attempts to extend this to amidations gave rise to only small amounts of the desired products. Reasoning that the use of a suitable co-catalyst was essential for the success of the amidation...

NHC-catalyzed oxidations using carbon dioxide as the stoichiometric oxidant have been carefully investigated. These studies support a secondary role of CO2 in suppressing side reactions and exogenous oxygen as the actual oxidant.