Enantioselective Synthesis of cis‐2,6‐Disubstituted‐4‐methylene Tetrahydropyrans via Chromium Catalysis†

Summary of main observation and conclusion Enantioenriched 2,6‐disubstituted 4‐methylene tetrahydropyrans have been obtained via a two‐step sequence consisting of a highly enantioselective chromium‐catalyzed carbonyl 2‐(trimethylsilyl methyl)allylation and Prins cyclization. Commercially available (2‐(chloromethyl)allyl)trimethylsilane serves as the bifunctional linchpin to combine two aldehydes to assemble the 2,6‐disubstituted pyrans. A variety of functional groups are compatible under the mild reaction conditions. The synthetic utility of this methodology was demonstrated by the asymmetric synthesis of 16 examples of homoallylic alcohol and 8 examples of 2,6‐disubstituted 4‐methylene tetrahydropyrans, including an advanced intermediate which could be transformed to natural product centrolobine via a known procedure.