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

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An efficient synthesis of the non-racemic (66–68% e.e.) homoallylic β-trifluoromethyl β-amino alcohol (2S,3R)-9, a key intermediate in the synthesis of trifluoromethylated dipeptide isosteres and oligopeptides, was developed starting from N-Cbz-trifluoropyruvaldehyde-N,S-ketal (R)-1a. The correct syn-stereochemistry was achieved by combining two moderately stereoselective steps: (1) addition of allylmagnesium chloride to (R)-1a, occurring with unusual nonchelation control; (2) reductive desulfenylation of the phenylacetate 6 with NaBH4/pyridine.