Trifluoromethyl- and difluoromethyl-β-lactams as useful building blocks for the synthesis of fluorinated amino acids, dipeptides, and fluoro-taxoids

Abstract

Enantiopure 1-acyl-3-hydroxyl-4-CF 2H-azetidin-2-ones and 1-acyl-3-hydroxy-4-CF 3-azetidin-2-ones serve as versatile intermediates for the syntheses of CF 2- and CF 3-containing α-hydroxy-β-amino acids, dipeptides, and taxoid anticancer agents. Both enantiomers of 3-hydroxy-4-CF 2H-β-lactams can be obtained in high yields through the diethylaminosulfur trifluoride (DAST) reaction of the corresponding enantiopure 4-formyl-β-lactam that is prepared through [2+2] cycloaddition of acetoxyketene to a 3-methyl-2-butenaldimine, followed by enzymatic optical resolution and ozonolysis. (+)-3-Hydroxy-4-CF 3-β-lactams and (−)-3-hydroxy-4-CF 3-β-lactams can also be readily obtained in enantiopure form through [2+2] cycloaddition of a CF 3-imine with a ketene, followed by enzymatic optical resolution. Practical processes for the preparations of these enantiopure 3-hydroxy-4-R f-β-lactams as well as their synthetic applications are described.