Highly stereoselective synthesis of aristeromycin through dihydroxylation of 4-aryl-L-azido-2-cyclopentenes

Dihydroxylation of 4-aryl-1-azido-2-cyclopentenes 6, in which an aryl group is used as a synthetic equivalent of CH2OH, was studied to improve the low to moderate stereoselectivity previously reported for cyclopentenes 3 possessing CH2X and nitrogen atom-containing groups. 2-Furyl, Ph, and p-MeOC6H4 groups were chosen as the aryl groups. Compounds 6a-c possessing such aryl groups were prepared by CuCN-catalyzed reaction between 2-cyclopentene-1,4-diol monoacetate 9 and the corresponding Grignard reagents followed by substitution of the hydroxyl group with (PhO)(2)P(=O)N-3. The desired diols 7a-c were obtained with higher selectivities of > 7:1 when dihydroxylation of 6a-c was carried out at 0degreesC with OsO4 (catalyst) and NMO in a mixed solvent of MeCN, THF, t-BuOH, and H2O. Among them, the furyl compound recorded the highest selectivity of 14:1. The furyl and azido groups on diol 7a were converted into hydroymethyl and adeninyl groups, respectively, to produce acetonide 2, which upon hydrolysis affords aristeromycin 1.