Unusual nonchelation controlled allylation of a N-monoprotected alpha-amino aldehyde: stereoselective entry to nonracemic trifluoromethyl dipeptide isosteres

An efficient synthesis of the non-racemic (66-68% e.e.) homoallylic beta -t rifluoromethyl beta -amino alcohol (2S,3R)-9, a key intermediate in the syn thesis of trifluoromethylated dipeptide isosteres and oligopeptides, was de veloped starting from N-Cbz-trifluoropyruvaldehyde-N,S-ketal (R)-1a. The co rrect syn-stereochemistry was achieved by combining two moderately stereose lective steps: (1) addition of allylmagnesium chloride to (R)-1a, occurring with unusual nonchelation control; (2) reductive: desulfenylation of the p henylacetate 6 with NaBH4/pyridine. (C) 2001 Elsevier Science B.V. All righ ts reserved.