Efficient Chiral Route to a Key Building Block of 1,25-Dihydroxyvitamin D3via Lipase-Mediated Resolution

Abstract
Racemic ethyl 5-hydroxy-1-cyclopentenecarboxylate [(±)-4] was resolved with complete enantiospecificity via kinetic acetylation in tert-butyl methyl ether in the presence of lipase PS which furnished optically pure (R)-acetate [(R)-5] and (S)-alcohol [(S)-4] both in nearly quantitative yields after silica gel column chromatography. (R)-Alcohol [(R)-4] obtained from (R)-5 was transformed into 1-ethynylbicyclo[3.1.0]hexan-2-one (3), a key building block of 1,25-dihydroxyvitamin D3 (1), in eight steps in 30% overall yield.

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