Glycosylidene carbenes. Part 22. α-D-Selectivity in the glycosidation by carbenes derived from 2-acetamido-hexoses

Article abstract of DOI:10.1002/hlca.19950780806

Glycosylidene carbenes derived from the GlcNAc and AllNAc diazirines 1 and 3 were generated by thermolysis or photolysis of the diazirines. The reaction of 1 with i-PrOH gave exclusively the isopropyl α-D-glycoside of 5 besides some dihydrooxazole 9. A similar reaction with (CF₃)₂CHOH yielded predominantly the α-D-anomer of 6, while glycosidation of 4-nitrophenol (→7) proceeded with markedly lower diastereoselectivity. Similarly, the allo-diazirine 3 gave the corresponding glycosides 12-14, but with a lower preference for the α-D-anomers. The reactions of the carbene derived from 1 with Ph₃COH (→8) and diisopropylideneglucose 10 (→11) gave selectively the α-D-anomers. The α-D-selectivity increases with increasing basicity (decreasing acidity) of the alcohols. It is rationalized by an intermolecular H-bond between the acetamido group and the glycosyl acceptor. This H-bond increases the probability for the formation of a 1,2-cis-glycosidic C-O bond. The gluco-intermediates are more prone to forming a N-H···(H)OR bond than the allo-isomers, since the acetamido group in the N-acetylallosamine derivatives forms an intramolecular H-bond to the cis-oriented benzyloxy group at C(3), as evidenced by δ/T and δ/c experiments.