The stereoselective replacement of hydroxyl groups by chlorine, using the mesyl chloride- N, N-dimethylformamide reagent

Abstract

The mesyl chloride- N, N-dimethylformamide reagent, previously described as selective for the replacement of primary hydroxyl groups by chlorine, has been shown to cause extensive, but selective, chlorination at secondary positions of glycopyranosides, particularly in the disaccharide series. Thus, reaction with methyl β-maltoside gave initially the 6,6′-dichloro derivative 2, which was then fairly rapidly transformed into the 3,6,6′-trichloro derivative 4. Further reaction, but at a slower rate, gave the 3,4′,6,6′-tetrachloro derivative 6. As anticipated, inversion of configuration accompanied reaction at positions C-3 and C-4′, indicating that the chlorine substituents were introduced by an S N2 mechanism. Benzyl β-cellobioside reacted to give a more-complex mixture from which the 6,6′-di-, 3′,6,6′-tri-, 3,6,6′-tri-, 4′,6,6′-tri-, 3,3′,6,6′-tetra-, and 3,4′,6,6′-tetra-chloro derivatives were isolated, after acetylation. Similarly, methyl glycopyranosides gave products of secondary chlorination, although the reaction proceeded less readily. Methyl α- D-glucopyranoside and methyl α- D-galactopyranoside gave the 4,6-dichloro-galactopyranoside and -glucopyranoside, respectively. On the other hand, methyl β- D-glucopyranoside gave a 2:1 mixture of methyl 3,6-dichloro-3,6-dideoxy-β- D-allopyranoside and methyl 4,6-dichloro-4,6-dideoxy-β- D-galactopyranoside. Structural elucidation of these chlorinated derivatives was based mainly on mass spectrometry and 220-MHz 1H n.m.r. spectroscopy.