Palladium-Catalyzed Enantioselective Synthesis of Carbanucleosides

A general strategy has been developed for enantioselective synthesis of diverse carbanucleosides. The key step is a Pd(0)-catalyzed enantioselective allylic amination of cis-3,5-dibenzoyloxycyclopent-2-ene 10a with the nucleobase. With guanine-derived nucleobase 13 and chiral ligand 9, a 93−96% ee was obtained, while 6-chloropurine and chiral ligand 8 gave 94% ee. The reaction was followed by a second Pd(0)-catalyzed allylic alkylation with phenylsulfonyl(nitro)methane 6. The nitrosulfone, thus obtained, served as a versatile intermediate for divergent synthesis in which the phenylsulfonyl(nitro)methyl group is a surrogate for the hydroxymethyl side chain. With the guanine-derived nucleobase 13, (−)-carbovir was obtained in only four steps from 10a. With 6-chloropurine as an adenine equivalent, the obtained nitrosulfone intermediate 26 could be converted into both (−)-aristeromycin and (−)-neplanocin A as well as their 2‘,3‘-diepi isomers.