A Diastereoselective Method for the Construction of syn-2′-Deoxy-2′-fluoronucleosides

A general and diastereoselective fluorination/glycosylation strategy for the synthesis of 2′-fluorinated nucleosides has been developed. Electrophilic fluorination of a glycal with NFSI provided the 1′,2′-difunctionalized furanoside intermediate with high diastereoselectivity. The TBS-protected 2′-deoxyfluorosulfonimide sugar was prepared on an 80 g scale and isolated as a crystalline, bench-stable single diastereomer. This intermediate was found to undergo a subsequent glycosylation reaction with a variety of heteroaryl nucleophiles with generally good diastereoselectivities.