Regio- and Enantioselective Synthesis of Chiral Pyrimidine Acyclic Nucleosides via Rhodium-Catalyzed Asymmetric Allylation of Pyrimidines

Abstract

A direct route to branched N-allylpyrimidine analogues is herein reported via the highly regio- and enantioselective asymmetric allylation of pyrimidines with racemic allylic carbonates. With [Rh(COD)Cl]₂/chiral diphosphine as the catalyst, a range of chiral pyrimidine acyclic nucleosides could be obtained under neutral conditions in good yields (up to 95% yield) with high levels of regio- and enantioselectivities (15:1 to >40:1 B/L and up to 99% ee). Furthermore, chiral pyrimidine acyclic nucleoside bearing two adjacent chiral centers has been successfully synthesized by asymmetric dihydroxylation.