Reported herein is the synthesis of all possible stereotriad propionates derived from L-lactic acid and L-alanine. The approach is based on a stereocontrolled Mukaiyama aldol reaction followed by a free radical-mediated hydrogen transfer, for which the choice of Lewis acid (monodentate or bidentate) dictates the stereochemical outcome in each reaction. The sequential process has been applied iteratively for the synthesis of eight stereopentad motifs derived from β,γ-alkoxyaldehydes. New experimental data and DFT calculations (BHandHLYP/TZVP) of the transition states involved in the radical reduction of aluminate intermediates support the proposed model of the endocyclic effect leading to high 2,3-syn selectivities for the synthesis of propionates and subunits thereof.
- This article is part of the themed collections: HOT articles in Organic Chemistry Frontiers for 2014 and In Celebration of Max Malacria’s 65th Birthday