An Enantioselective Decarboxylative Glycolate Aldol Reaction

The development of catalytic enantioselective aldol reactions has been at the forefront of advancements in contemporary asymmetric methodology. Despite significant progress, the catalytic enantioselective synthesis of certain synthetically important motifs such as the ubiquitous aliphatic syn-diol remains a challenge. Herein, we report the application of a benzyloxy-functionalized malonic acid half thioester as an activated ester equivalent in a highly enantioselective glycolate aldol reaction. This robust method operates at ambient temperature, tolerates air and moisture, and generates CO2 as the only by-product. The synthetic applicability of the method is demonstrated by the large-scale enantiodivergent synthesis of -benzyloxy-β-hydroxybutyric acid thioester and its subsequent conversion to diverse polyoxygenated building blocks, deoxy-sugars, and the natural product (–)-angiopterlactone B.