Synthesis of methylene acetals in the d-glucose, d-galactose, d-mannose, and d-fructose series by an improved transacetalation reaction from dimethoxymethane

✍ Scribed by Robert Nouguier; Valérie Mignon; Jean-Louis Gras

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 402 KB
• Volume: 277
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(95)00218-i

✦ Synopsis

Although methylene acetals of sugars can be synthesized by reaction with formaldehyde in an acidic medium [1] or with dihalomethanes in an alkaline medium [2], they are far less popular than the isopropylidene, benzylidene, or ethylidene acetal derivatives [3]. This may be due to the higher resistance to acid cleavage of the methylene acetal protective group compared with the latter. This higher stability may prove advantageous, for instance if the protected carbohydrate is used as an "off-template" chiral molecule for asymmetric induction in the presence of a Lewis acid [4]. D-Glucose and D-galactose led to the corresponding 1,2:3,4-dimethylene acetal when reacted with formaldehyde in an acidic medium [lb,c,f], and D-ribose led to the 2,3-O-isopropylidene-l,5-O-methylene-/3-D-ribofuranose in the presence of acetone, formaldehyde, and sulfuric acid [5]. When applied to methyl a-or fl-D-glycopyranosides, this methodology led to 4,6-0methylene-D-glycopyranosides in very low yields (3.4-13.6%) [le].

Dimethoxymethane (DMM) has been used as a substitute to chloromethyl methyl ether for the protection of alcohols [6], and to formaldehyde for the synthesis of methylene acetals of diols and alditols [7].