Enantiomeric synthesis of 3′-fluoro-apionucleosides using Claisen rearrangement

Enantiomeric synthesis of 3′-fluoro-apionucleosides was accomplished from 1,2-O-isopropylidene D-glyceraldehyde. The key intermediate, γ,δ-unsaturated tert-fluoro ethyl ester 7 from the fluoro allylic alcohol derivative 5 was achieved via Claisen rearrangement reaction with a 90.4% enantioselectivity. The condensation of the intermediate 10 with silylated N⁴-benzoylcytosine and 6-chloropurine followed by deprotection gave the desired pyrimidine and purine apionucleosides, respectively.