Asymmetric supramolecular catalysis: A bio-inspired tool for the high asymmetric induction in the enamine-based Michael reactions

Abstract

A new and efficient supramolecular catalysis was designed for the asymmetric Michael reaction of cyclohexanone with 2-(2-nitrovinyl)phenols to give the desired hexahydroxanthenols 5 with high yield, enantiomeric excess (ee) and diastereoisomeric excess (de) values. The reaction yielded the anticipated opposite enantiomer of (+)-6aa in 86% yield after two steps with a little compromise in enantioselectivity of 96% ee and 98% de. The lactols were isolated in 92-95% de at the Michael-reaction stage, but were found to get enriched to < 99% de after the reductive etherification reaction may be due to the decomposition or hydrolysis of minor isomer of lactols. To further understand the direction of hypothetical pre-TS supramolecular assembly, the Michael reaction was performed with opposite catalysts combination of l-proline 3b and quinidine-NH-thiourea. The structure and absolute stereochemistry of the Michael products, reductive etherification products, and chromenes were confirmed by NMR spectroscopy analysis.