A Diastereoselective Method for the Construction of syn-2'-Deoxy-2'-fluoronucleosides
Michael T Pirnot1, Edna Mao1, Yu-Hong Lam2
1Department of Process Research and Development, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States.
Abstract:
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.
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