Direct synthesis of diastereomerically pure glycosyl sulfonium salts

Abstract

It is reported that stable glycosyl sulfonium salts can be generated via direct anomeric S-methylation of ethylthioglycosides. Mechanistically, this pathway represents the first step in the activation of thioglycosides for glycosidation; however, it can further allow for the synthesis and isolation of quasi-stable sulfonium ions, representing a new approach for studying these key intermediates.

Figure 1

Structures of sulfonium salts 2d^a, 2d^b, 2e and 2f.

Scheme 1

Glycosidation of thioglycosides

Scheme 2

Glycosyl sulfonium ions: (a) obtained via anomeric triflate;^, (b) bicyclic sulfonium ions;^- (c) obtained via direct methylation of the leaving group (this work).

Scheme 3

Unexpectedly low yield of disaccharide 5.

Scheme 4

Formation and hydrolysis of salt 2a monitored by 300 MHz ¹H NMR in CDCl₃.