Enantioselective Syntheses of Carbanucleosides from the Pauson-Khand Adduct of Trimethylsilylacetylene and Norbornadiene

A new enantioselective approach to carbanucleosides from Pauson-Khand (PK) adduct 1 is disclosed. The chiral cyclopentenone 1 is readily accessible in enantiomerically pure form via PK reaction of trimethylsilylacetylene and norbornadiene using N-benzyl-N-diphenylphosphino-tert-butyl-sulfinamide as a chiral P,S ligand. (−)-Carbavir and (−)-Abacavir were enantioselectively synthesized starting from (−)-1. The key steps of the sequence are a photochemical conjugate addition of a hydroxymethyl radical, a retro-Diels−Alder reaction, and a palladium catalyzed allylic substitution to introduce the nucleobase.