Glycosylidene Carbenes. Part 19. Regioselective glycosidation of allyl 2‐deoxy‐2‐phthalimido‐D‐allopyranosides

Abstract

The regio‐ and stereoselectivity of the glycosidation of the partially protected mono‐alcohols 3 and 7, the diols 2 and 8, and the triol 4 by the diazirine 1 have been investigated. Glycosidation of the α‐D‐diol 2 (Scheme 2) gave regioselectively the 1,3‐linked disaccharides 11 and 12 (80%, α‐D/β‐D 9:1), whereas the analogous reaction with the βD‐anomer 8 led to a mixture of the anomeric 1,3‐ and 1,4‐linked disaccharides 13 (12.5%), 14 (16%), 15 (13%), and 16 (20.5%; Table 2). Protonation of the carbene by OH–C(4) of 2 is evidenced by the observation that the α‐D‐mono‐alcohol 3 did not react with 1 under otherwise identical conditions, and that the β‐D‐alcohol 7 yielded predominantly the β‐D‐glucoside 18 (52%) besides 14% of 17. Similarly as for the glycosidation of the diol 2, the influence of the H‐bond of HOC(4) on the direction of approach of the carbene, the role of HOC(4) in protonating the carbene, and the stereoelectronic control in the interception of the ensuring oxycarbenium cation are evidenced by the reaction of the triol 4 with 1 (Scheme 3), leading mostly to the α‐D‐configurated 1,3‐linked disaccharide 19 (41%), besides its anomer 20 (16%), and some 4‐substituted β‐D‐glucoside 21 (9%). No 1,6‐linked disaccharides could be detected. In agreement with the observed reactivity, the ¹H‐NMR and IR spectra reveal a strong H‐bond between HOC(3) and the phthalimido group in the α‐D‐, but not in the β‐D‐allosides. The different H‐bonds in the anomeric phthalimides are in keeping with the results of molecular‐mechanics calculations.