Synthesis of nonracemic alpha-trifluoromethyl alpha-amino acids from sulfinimines of trifluoropyruvate

We describe a novel and useful method for the synthesis of nonracemic alpha -trifluoromethyl alpha -amino acids (alpha -Tfm-AAs). Key building blocks are the sulfinimines (S)-1a and (S)-1b, prepared by Staudinger reaction fro m trifluoropyruvate esters and the chiral N-sulfinyl iminophosphorane (S)-8 , which were treated with benzyl, allyl, and alkylmagnesium halides. The re sulting diastereomeric N-sulfinyl alpha -Tfm alpha -amino esters, 12 and 13 , were produced with moderate to good stereoselectivity and yields. When al kyl Grignard reagents were used, stereocontrol became progressively higher with increasing steric bulk, while reversed, though poor, stereocontrol was achieved with benzyl/allyl Grignard reagents. An explanation for the obser ved stereochemical outcome is proposed, on the basis of the exclusive E geo metry (N-sulfinyl and CF, trans about the C=N bond) of the chiral sulfinimi nes 1. This assignment is the product of structural correlation and is supp orted by ab initio calculations and NOE experiments. Sulfinamides 12 and 13 were transformed into a series of nonracemic alpha -Tfm-AAs 16-22. The sul finyl auxiliary can be regenerated and recycled.