Synthesis of 1,2‐cis‐Configurated Glycosylphosphonates

A synthesis of 1,2‐cis‐configurated, non‐isosteric phosphonate analogues of aldose‐1‐phosphates is described. Treatment of 1‐O‐acyl‐glycoses 1, 7, 13, and 19 with trialkyl phosphite in the presence of trimethylsilyl trifluoromethanesulfonate gave the 1,2‐cis‐configurated glycosylphosphonates 2, 4, 8, 10, 14, 16, 20, and 22 as the major anomers and the 1,2‐trans‐configurated glycosylphosphonates 3, 5, 9, 11, 15, 17, 21, and 23 as the minor anomers. The 1,2‐cis‐configurated phosphonates 4, 10, 16, and 22 were deprotected to give the (β‐D‐glucopyranosyl)phosphonate 6, the (β‐D‐mannopyranosyl)phosphonate 12, the (β‐D‐ribofuranosyl)phosphonate 18, and the (β‐D‐arabinofuranosyl)phosphonate 24, respectively, in high yields. The preferred formation of 1,2‐cis‐configurated phosphonates is explained by postulating an equilibrium between the anomeric phosphonium‐salt intermediates (such as 25 and 26) and a stabilization of the cis‐configurated salts through formation of a pentacoordinated species (such as 28).