Imine Directed CpRhIII-Catalyzed N-H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds

A multicomponent annulation that proceeds by imine directed Cp*Rh-III-catalyzed N-H functionalization is disclosed. The transformation affords piperazinones displaying a range of functionality and is the first example of transition metal-catalyzed multicomponent N-H functionalization. A broad range of readily available alpha-amino amides, including those derived from glycine, alpha-substituted, and alpha,alpha-disubstituted amino acids, were effective inputs and enabled the incorporation of a variety of amino acid side chains with minimal racemization. Branched and unbranched alkyl aldehydes and various stabilized diazo compounds were also efficient reactants. The piperazinone products were further modified through efficient transformations. Mechanistic studies, including X-ray crystallographic characterization of a catalytically competent five-membered rhodacycle with imine and amide nitrogen chelation, provide support for the proposed mechanism.

Automated summary

A multicomponent annulation that proceeds by imine directed Cp*Rh-III-catalyzed N-H functionalization has been developed, which provides piperazinones with a range of functionality. This is the first example of transition metal-catalyzed multicomponent N-H functionalization. Mechanistic studies support the proposed mechanism and the efficient transformation of the piperazinone products.