Oxazoline-oxazinone oxidative rearrangement. Divergent syntheses of (2S,3S)-4,4,4-trifluorovaline and (2S,4S)-5,5,5-trifluoroleucine

Julie A. Pigza, Tim Quach, Tadeusz F. Molinski

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

(Chemical Equation Presented) 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- methylbutanoic acid by using a conceptually simple transformation: conversion to a chiral oxazoline, SeO2-promoted oxidative rearrangement to the dihydro-2H-oxazinone, and face-selective hydrogenation of the C=N bond, followed by hydrogenolysis-hydrolysis. The transformation is limited by the tendency of the intermediate β-trifluoromethyldihydrooxazinone to undergo imine-enamine isomerization. Both amino acids were obtained as configurationally pure hydrochloride salts identical in all respects with those in literature reports.

Original languageEnglish
Pages (from-to)5510-5515
Number of pages6
JournalThe Journal of Organic Chemistry
Volume74
Issue number15
DOIs
Publication statusPublished - 7 Aug 2009
Externally publishedYes

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