Asymmetric Synthesis Based on (2R,3S)-3,4-Dimethyl-2-phenylperhydro-1,4-oxazepine-5,7-dione. Synthesis of Highly Optically Active β-Substituted Alkanoic Acids

Abstract

Abstract A general method was worked out for the preparation of highly optically pure β-substituted alkanoic acids from aldehydes with use of (2R,3S)-6-alkylidene-3,4-dimethyl-2-phenylperhydro-1,4-oxazepine-5,7-diones(2) as key intermediates. Oxazepines(2) were prepared in high yields by treating aldehydes with (2R,3S)-3,4-dimethyl-2-phenylperhydro-1,4-oxazepine-5,7-dione(1) in the presence of titanium tetrachloride. The conjugate addition of Grignard reagents to 2 in the presence of nickel chloride, followed by hydrolysis and decarboxylation afforded highly enantiomerically pure β-substituted alkanoic acids in good yields. The addition of lithium dialkylcuprate to 2 was examined. It was found that (S)-(+)-3-phenylheptanoic acid is obtained by the reaction of lithium dibutylcuprate with (E)- and (Z)-6-benzylidene derivatives of 1, respectively.