Enzymatic Resolution of O ‐(Methoxymethyl)‐Protected Tropane‐diols

A convenient synthetic route to enantiomerically pure tropane‐diol building blocks is described. The reaction sequence started from tropenone derivatives 1 , which were dihydroxylated to give 6,7‐dihydroxytropanone derivatives 2 . After introduction of the methoxymethyl (MOM) protecting group in diol 2a , a lipase‐mediated resolution of the resulting racemic mono‐MOM ether (±)‐ 5d with vinyl acetate and vinyl trifluoroacetate gave the acetates (−)‐ 6d and (−)‐ 6f , respectively, with 96–99% ee, and MOM ether (+)‐ 5d with up to 89% ee. Deacetylation of (−)‐ 6d afforded quantitatively MOM ether (−)‐ 5d with 99% ee, the absolute configuration of which was assigned via the modified Mosher method to be ( R ) at C(6). Enzymatic treatment of unprotected diol 2a with vinyl trifluoroacetate or alkoxycarbonylation resulted in the formation of C s ‐symmetrical products 9 and 12 rather than the desired desymmetrized derivatives.