Oxazoline-oxazinone oxidative rearrangement. divergent syntheses of (2S,3S)-4,4,4-trifluorovaline and (2S,4S)-5,5,5-Trifluoroleucine.
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 beta-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.
Pigza
Julie A
JA
The Department of Chemistry and Biochemistry and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Quach
Tim
T
Molinski
Tadeusz F
TF
D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D010078:Oxazines / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D010078:Oxazines; D010080:Oxazoles; C452360:4,4,4-trifluorovaline; C035177:5',5',5'-trifluoroleucine; D007930:Leucine; D014633:Valine