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

Enantiopure 1-acyl-3-hydroxyl-4-CF2H-azetidin-2-ones and 1-acyl-3-hydroxy-4-CF3-azetidin-2-ones serve as versatile intermediates for the syntheses of CF2- and CF3-containing alpha-hydroxy-beta-amino acids, dipeptides, and taxoid anticancer agents. Both enantiomers of 3-hydroxy-4-CF2H-beta-lactams can be obtained in high yields through the diethylaminosulfur trifluoride (DAST) reaction of the corresponding enantiopure 4-formyl-beta-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-CF3-beta-lactams and (-)-3-hydroxy-4-CF3-beta-lactams can also be readily obtained in enantiopure form through [2 + 2] cycloaddition of a CF3-imine with a ketene, followed by enzymatic optical resolution. Practical processes for the preparations of these enantiopure 3-hydroxy-4-R-f-beta-lactams as well as their synthetic applications are described. (C) 2003 Elsevier B.V. All rights reserved.