Diastereoselective synthesis of trans-trifluoromethyl-β-lactams and α-alkyl-β-trifluoromethyl-β-amino esters

The diastereoselective synthesis of β-lactams was examined from N-tosyl-1-chloro-2,2,2-trifluoroethylamine 3 and various nonactivated aliphatic acid chlorides in the presence of a Brønsted base. The mild reaction conditions allowed to get trifluoromethyl-β-lactams in good yields with high trans-diastereo selectivity. In addition, we also demonstrated that ring-opening of β-lactams easily provided α-alkyl-β-trifluoromethyl-β-amino esters.

Graphical abstractA new, one-pot method for synthesis of fluorinated β-lactams has been developed from N-tosyl-1-chloro-2,2,2-trifluoroethylamine and various nonactivated aliphatic acid chlorides in the presence of dimethylethylamine. The reaction is highly diastereoselective providing the trans-lactams that could be further transformed into α-alkyl-β-trifluoromethyl-β-amino esters. Download full-size image