Synthesis of γ-Butyrolactones with Chiral Quaternary-Tertiary Stereocenters via Catalytic Asymmetric Mukaiyama-Michael Addition

Org Lett. 2024 Nov 4. doi: 10.1021/acs.orglett.4c03373. Online ahead of print.

Abstract

A catalytic asymmetric Mukaiyama-Michael reaction of silyl ketene acetals (SKAs) with α- or β-substituted α,β-unsaturated pyrazolamides was realized with N,N'-dioxide/nickel(II) complex catalysts. Bidentate coordination of the substrate to the catalyst and elongation of the ligand were beneficial for stereocontrol. In addition, adjustment of the substituents on substrates tuned the reactivity significantly. A wide range of chiral γ-butyrolactones with quaternary-tertiary stereocenters were obtained in moderate to excellent yields, good diastereomeric ratio, and excellent enantiomeric excess values.