Asymmetric Construction of Remote Vicinal Quaternary and Tertiary Stereocenters via Direct Doubly Vinylogous Michael Addition.

Abstract

An asymmetric direct doubly vinylogous Michael addition has been developed for the generation of sterically congested vicinal quaternary and tertiary stereocenters. This doubly vinylogous Michael addition of β,γ-unsaturated butenolides to 3-methyl-4-nitro-5-alkenyl isoxazoles, powered by a bifunctional squaramide, affords a broad range of densely functionalized enantioenriched γ,γ-disubstituted butenolides in high yields with excellent diastereo- and enantioselectivities in most cases. Moreover, the strategy highlights the first application of β,γ-unsaturated butenolides in an asymmetric 1,6-conjugate addition.