Asymmetric Hydrogenation of α‑Purine Nucleobase-Substituted Acrylates with Rhodium Diphosphine Complexes: Access to Tenofovir Analogues

The first asymmetric
hydrogenation of α-purine nucleobase-substituted
α,β-unsaturated esters, catalyzed by a chiral rhodium
(R)-Synphos catalyst, has been developed. A wide
range of mono- and disubstituted acrylates were successfully hydrogenated
under very mild conditions in high yields with good to excellent enantioselectivities
(up to 99% ee). This method provides a convenient approach to the
synthesis of a new kind of optically pure acyclic nucleoside and Tenofovir
analogues.