Catalytic Asymmetric Synthesis of Acyclic Arrays by Tandem 1,4-Addition-Aldol Reactions

Herein, we report efficient acyclic stereocontrol in tandem 1,4-addition-aldol reactions triggered
by catalytic asymmetric organometallic addition. Grignard reagents add to α,β-unsaturated thioesters in a
1,4-fashion and the resulting magnesium enolates are trapped with aromatic or aliphatic aldehydes. The
process provides a range of tandem products bearing three contiguous stereocenters with excellent control
of relative and absolute stereochemistry. The various diastereomeric products have been fully characterized
using single-crystal X-ray analysis and the origins of stereocontrol in this tandem protocol are discussed.
The versatility and efficiency of this methodology are demonstrated in the first catalytic asymmetric synthesis
of (−)-phaseolinic acid with 54% overall yield via a short and concise route.