Oxazoline-Oxazinone Oxidative Rearrangement. Divergent Synthesesof (2S,35)-4,4,4-Trifluorovaline and (2S,4S)-5,5,5-Trifluoroleucine

摘要

Stereoselective syntheses of the valuable fluorinated amino acids (2S,3S)-4,4,4-trifluorovaline and(2S,4S)-5,5,5-trifluoroleucine have been achieved starting from 4,4,4-trifluoro-3-methylbutanoicacid by using a conceptually simple transformation: conversion to a chiral oxazoline, SeO_2-promotedoxidative rearrangement to the dihydro-2H-oxazinone, and face-selective hydrogenation of the C=Nbond, followed by hydrogenolysis-hydrolysis. The transformation is limited by the tendency of theintermediate β-trifluoromethyldihydrooxazinone to undergo imine-enamine isomerization. Bothamino acids were obtained as configurationally pure hydrochloride salts identical in all respects withthose in literature reports.