N,N'-Diamidocarbenes: Isolable Divalent Carbons with Bona Fide Carbene Reactivity

Since the first reported isolation of a carbene just over a quarter century ago, the study of such compounds-including stable derivatives-has flourished. Indeed, N-heterocyclic carbenes (NHCs), of which imidazolylidenes and their derivatives are the most pervasive subclass, feature prominently in organocatalysis, as ligands for transition metal catalysts, and as stabilizers of reactive species. However, imidazolylidenes (and many other NHCs) typically lack the reactivity characteristic of electrophilic carbenes, including insertion into unactivated C-H bonds, participation in [2 + 1] cycloadditions, and reaction with carbon monoxide. This has led to debates over whether NHCs are truly carbenic in nature or perhaps better regarded as ylides. The fundamental and synthetic utility of transformations that involve electrophilic carbenes has motivated our group and others to expand the reactivity of NHCs and other stable carbenes to encompass electrophilic carbene chemistry. These efforts have led to the development of the diamidocarbenes (DACs), a stable and unique subset of the NHCs that feature carbonyl groups inserted into the N-heterocyclic scaffold. To date, crystalline five-, six-, and seven-membered DACs have been prepared and studied. Unlike imidazolylidenes, which are often designated as prototypical NHCs, the DACs exhibit a reactivity profile similar to that of bona fide carbenes, reactive species that are less "tamed" by heteroatom π conjugation. The DACs engage in [2 + 1] cycloadditions with electron-rich or -poor alkenes, aldehydes, alkynes, and nitriles, and doing so in a reversible manner in some cases. They also react with isonitriles, reversibly couple to CO, and mediate the dehydrogenation of hydrocarbons. Such rich chemistry may be rationalized in terms of their ambiphilicity: DACs are nucleophilic, as required for some of the reactions above, yet also have electrophilic character, as evidenced by their insertions into unactivated N-H and C-H bonds, including nonacidic derivatives. As will become clear, such reactivity is unique among isolable carbenes. DAC chemistry is expected to find applications in synthesis, dynamic covalent chemistry, and catalysis. For example, the hydrolysis of DAC-derived diamidocyclopropanes and -propenes affords carboxylic acids and cyclopropenones, respectively. These new hydrocarboxylation and carbonylation methodologies are significant in that they represent alternatives to processes that typically involve precious metals and gaseous carbon monoxide. Future efforts in this area may involve modifications that transform the stoichiometric conversions facilitated by DACs into catalytic variants. In this context, the reversible binding of CO to DACs is an indication that the latter may serve as a blueprint for the development of more electrophilic, stable carbenes with the capacity to activate other challenging small molecules.