Interplay between Organocatalysis and Multicomponent Reactions in Stereoselective Synthesis

Author(s)

Rivera, Daniel G. ; Paixao, Marcio W. ; Cheng, HN ; Maryanoff, CA ; Miller, BD ; Schmidt, DG

• Document type: Journal article
• Source: STEREOCHEMISTRY AND GLOBAL CONNECTIVITY: THE LEGACY OF ERNEST L ELIEL, VOL 2; v. 1258, p. 12-pg., 2017-01-01.

Abstract

Multicomponent reactions (MCRs) serve as powerful approaches for the synthesis of bioactive heterocyclic compounds and natural products. Owing to their high chemical efficiency, atom economy and diversity -generating character, these processes have been intensively exploited in drug discovery and chemical biology programs. As chiral ketones and aldehydes are key components in stereocontrolled MCRs, methods for the asymmetric functionalization of carbonyl compounds are relevant for the development of novel stereoselective multicomponent approaches. In the last decade, oraanocatalysis has been successful in the alpha-, beta-, gamma and even epsilon-asymmetric functionalization of carbonyls, thus showing promise for its combination with MCRs in the pursuit of highly stereoselective cascade sequences. This chapter highlights a recent international endeavor that combines the diversity and complexity-generating character of MCRs with the high stereoselection of organocatalysis for the synthesis of enantiomerically pure compounds. The reaction sequences comprise the asymmetric aminocatalytic functionalization of alpha,beta-unsaturated aldehydes followed by isocyanide-MCRs with such oxo-components as chiral inputs. Methods described herein provide a convergent and stereoselective way of producing natural product-like compounds such as hydroquinolines, chromenes, epoxy- and depsi-peptides. (AU)

• FAPESP's process: 15/17141-1 - Development and Mechanism Studies of New Synthetic Methodologies for the Synthesis of Bioactive Compounds.
• Grantee: Ricardo Samuel Schwab
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Grants - Research Centers in Engineering Program