Palladium-catalyzed enantioselective synthesis of carbanucleosides

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