Stereoselective β-mannosylations and β-rhamnosylations from glycosyl hemiacetals mediated by lithium iodide

Stereoselective beta-mannosylation is one of the most challenging problems in the synthesis of oligosaccharides. Herein, a highly selective synthesis of beta-mannosides and beta-rhamnosides from glycosyl hemi-acetals is reported, following a one-pot chlorination, iodination, glycosylation sequence employing cheap oxalyl chloride, phosphine oxide and LiI. The present protocol works excellently with a wide range of glycosyl acceptors and with armed glycosyl donors. The method doesn't require conformationally restricted donors or directing groups; it is proposed that the high beta-selectivities observed are achieved via an S(N)2-type reaction of alpha-glycosyl iodide promoted by lithium iodide.

Automated summary

This method employs a one-pot chlorination, iodination, glycosylation sequence using inexpensive oxalyl chloride, phosphine oxide and LiI to achieve highly selective synthesis of beta-mannosides and beta-rhamnosides from glycosyl hemi-acetals. The high selectivities observed are proposed to be achieved via an S(N)2-type reaction of alpha-glycosyl iodide promoted by lithium iodide, without requiring conformationally restricted donors or directing groups.