The aldol reaction is among the most powerful and strategically important carbon–carbon bond–forming transformations in organic chemistry. The importance of the aldol reaction in constructing chiral building blocks for complex small-molecule synthesis has spurred continuous efforts toward the development of direct catalytic variants. The realization of a general catalytic aldol reaction with control over both the relative and absolute configurations of the newly formed stereogenic centers has been a longstanding goal in the field. Here, we report a decarboxylative aldol reaction that provides access to all four possible stereoisomers of the aldol product in one step from identical reactants. The mild reaction can be carried out on a large scale in an open flask, and generates CO2 as the only by-product. The method tolerates a broad substrate scope and generates chiral β-hydroxy thioester products with substantial downstream utility.
