Beyond Protecting Groups in Metal Catalyzed C–C Coupling: Direct Anomeric Propargylation of Aldoses

Since the seminal work of Butlerov (1863) 1a and Grignard (1900), the addition of preformed organometallic reagents to carbonyl compounds has played a central role in chemical synthesis. While this technology has opened vast volumes of chemical space, the basicity of most organometallic reagents mandates “protection” of acidic substructures, including the ubiquitous hydroxyl group. For the synthesis of carbohydrates, polyhydroxylated compounds bearing multiple stereogenic centers, catalystdirected stereoselective carbonyl addition in the absence of protecting groups has only been achieved using enzymes. In a groundbreaking advance, Shimizu and Kanai have devised conditions for the direct anomeric propargylation of unprotected aldoses with excellent levels of catalyst-directed diastereoselectivity. This technology enables concise access to diverse sialic acids (important cell-surface signaling molecules) and represents a powerful addition to the lexicon of methods for protecting-group-free chemical synthesis.