Stereoselective synthesis of β-amino-γ-butyrolactones

A novel synthesis of optically active beta-amino-gamma-butyrolactones is described. O-Silylated (R)-cyanohydrins (R)-3 (derived from aldehydes 1 by (R)-hydroxynitrile lyase ((R)-PaHNL)-catalyzed addition of HCN) were reacted with allyl Grignard to give amino alcohols (4R,5S)-5 after reduction. In the addition of crotyl Grignard reagent, workup conditions are decisive for the formation of amino alcohol 8, which was isolated Lis a diastercoisomeric mixture the acetylated main diastereoisomer (3S,4R,5R)-10 was separated. Ozonolysis of the acetylated amino alcohols (4S,5R)-7a,b and (3S,4S,5R)-10 affords the aldehydes 12a-c, which were directly oxidized with CrO3 in dilute H2SO4 to yield the beta-acetamido-gamma-acetoxycarboxylic acids (3S,4R)-13a,b and (2R,3S,4R)-13c. Compounds 13 cyclized spontaneously Under acidic conditions to afford beta-acetamido-gamma-butyrolactones (4S,5R)-14a,b and (3R,4S,5R)-14c. (C) 2002 Elsevier Science Ltd. All rights reserved.