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Herein, we report efficient acyclic stereocontrol in tandem 1,4-addition-aldol reactions triggered by catalytic asymmetric organometallic addition. Grignard reagents add to alpha,beta-unsaturated thioesters in a 1,4-fashion and the resulting magnesium enolatesare 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.

(-)-Phaseolinic acid is a metabolite of a fungus, Macrophomina phaseolina, and (-)-methylenolactocin is an antitumoral antibiotic from Penicillum sp. In the course of our studies aimed at the synthesis of enantiomerically pure g-butyrolactones4 we focused our attention on the synthesis of both enantiomers of phaseolinic acid and on the determination of their absolute configuration by means of chemical and spectroscopic correlations. The strategy was to correlate (-)-phaseolinic acid with (-)-methylenolactocin