Imine Directed Cp*Rh^III‐Catalyzed N−H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds

Abstract

A multicomponent annulation that proceeds by imine directed Cp*Rh III -catalyzed NÀ H functionalization is disclosed. The transformation affords piperazinones displaying a range of functionality and is the first example of transition metal-catalyzed multicomponent NÀ H functionalization. A broad range of readily available α-amino amides, including those derived from glycine, α-substituted, and α,α-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.

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

“…Classical multicomponent reactions are well known by their proper name and scope: Ugi [ 4 , 9 ], Passerini [ 6 , 10 ], van Leusen [ 11 , 12 ], Strecker [ 13 ], Orru [ 14 ], Mannich [ 6 , 15 ], Biginelli [ 6 , 16 , 17 ] and Hantzsch syntheses [ 6 , 18 ] need to be mentioned. However, the discovery of new multicomponent reactions is an active research field [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], with novel exciting MCRs being discovered and incorporated to the synthetic armamentarium every year. Among these MCRs with transition metal catalysis [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ], radical process [ 7 , 21 , 35 , 36 ] and organo-catalysis [ 37 , 38 , 39 , 40 , 41 ] should also be mentioned.…”