A practical synthesis of enantiopure 4,4,4-trifluoro-allo-threonine from an easily available fluorinated building block

Abstract

A practical method to prepare enantiopure 4,4,4-trifluoro-allo-threonine was developed by using an easily available fluorinated building block and a chiral auxiliary as starting materials. Trifluoroacetic anhydride was annulated with a ketene, derived from a glycine equivalent bearing a chiral oxazolidinone [(4S,5R)-4,5-diphenyloxazolidin-2-one], and acetone to afford a trifluoromethylated α,β-unsaturated lactone. The asymmetric hydride reduction of the α,β-unsaturated lactone proceeded with excellent stereoselectivity to give the corresponding (2R,3S)-4-oxapentan-5-olide derivative exclusively (diastereopurity, 99%). From the reduced product thus obtained, protecting groups were readily removed by acid treatment and subsequent catalytic hydrogenolysis to afford enantiopure (2R,3S)-4,4,4-trifluoro-allo-threonine in an excellent yield (7 steps, 51% overall yield).