Efficient and β-Stereoselective Synthesis of 4(5)-(β-d-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles1

A synthetic route to 4(5)-(β-d-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-d-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N‘,N‘-tetramethylazodicarboxamide and Bu3P exclusively afforded benzylated β-ribofuranosyl imidazole 9β in 92% yield, accompanied by α-anomer 9α, in a ratio of 26.3:1. The configuration of 9β was established by X-ray crystallography of ethoxycarbonyl derivative 10β. Reductive debenzylation of 9β over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-β-d-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced ...