Solvent Dependent Competitive Mechanisms for the Ugi Multicomponent Reaction: A Joint Theoretical and Experimental Study in the α-Acyl Aminocarboxamides vs α-Amino Amidines Formation.

Marcelo H R Carvalho, João P R S Ribeiro, Pedro P De Castro, Saulo T A Passos, Brenno A D Neto, Hélio F Dos Santos, Giovanni W Amarante

The Journal of organic chemistry 2022 Aug 19

filter terms:

A synthetic protocol for the preparation of α-acyl aminocarboxamides and α-amino amidines is proposed. The selectivity toward each of these two possible products was tuned by simple modifications of the reaction conditions. A broad scope is presented, allowing access to the desired products in up to 87% (Ugi adduct) and 93% (α-amino amidine). Theoretical calculations were carried out, and the analysis led to the proposal of a new mechanistic pathway for the Ugi reaction, in which methanol acts not only as the solvent but also as a reagent. High-resolution (tandem) mass spectrometry experiments allowed the detection and characterization of the key intermediate associated with this new and alternative reaction pathway, thus supporting the theoretical proposal.

Citation

Marcelo H R Carvalho, João P R S Ribeiro, Pedro P De Castro, Saulo T A Passos, Brenno A D Neto, Hélio F Dos Santos, Giovanni W Amarante. Solvent Dependent Competitive Mechanisms for the Ugi Multicomponent Reaction: A Joint Theoretical and Experimental Study in the α-Acyl Aminocarboxamides vs α-Amino Amidines Formation. The Journal of organic chemistry. 2022 Aug 19;87(16):11007-11020