GLYCOSYLIDENE CARBENES .2. SYNTHESIS OF O-ARYL GLYCOSIDES

Phenol, 4‐methoxyphenol, 4‐nitrophenol, methyl orsellinate (1), and 2,6‐di(tert‐butyl)‐4‐methylphenol (BHT; 2) have been glycosylated by thermal reaction (20–60°) with various glycosylidene‐derived diazirines. 4‐Methoxyphenol reacted with the D‐glucosylidene‐derived diazirine 3 to give O‐glucosides (4 and 5, 69%, 3:1) and C‐glucosides (6 and 7, 16%, 1:1). Similarly, phenol yielded O‐glucosides (10 and 11, 70%, 4:1) and C‐glucosides (12 and 13, 13%, 1:1). 4‐Nitrophenol gave only O‐glycosides, 3 leading to 14 and 15 (75%, 3:2; Scheme 1), and the D‐galactosylidene‐derived diazirine 17 to 22 and 23 (52% (from 16), 65:35; Scheme 2). The reaction of phenol with 17 yielded 58% (from 16) of the O‐galactosides 18 and 19 (4:1) and 14% of the C‐galactosides 20 and 21 (1:1). From the D‐mannosylidene‐derived diazirine 25, we predominantly obtained the α‐D‐configurated 26 (38 % from 24). These results are interpreted by assuming that an intermediate (presumably a glycosylidene carbene) first deprotonates the phenol to generate an ion pair which combines to give O‐ and ‐ with electron‐rich phenolates ‐ also C‐glycosides. A competition experiment of 3 with 4‐nitro‐ and 4‐methoxyphenol gave the products from the former (14 and 15) and the latter phenol (4‐7) in almost equal amounts. Differences in the kinetic acidity of OH groups, however, may form the basis of a regioselective glycosidation, as evidenced by the reaction of 3 with methyl orsellinate (1) yielding exclusively the 4‐O‐monoglycosylated products 27 and 28 (78%, 85:15), although diglycosidation is possible (27→ 31 and 32; 67%, 4:3; Scheme 3). Steric hindrance does not affect this type of glycosidation; 3 reacted with the hindered BHT (2) to afford 33 and 34 (81 %, 4:1). The predominant formation of 1,2‐trans ‐configurated O‐aryl glycosides is rationalized by a neighbouring‐group participation of the 2‐benzyloxy group. Copyright © 1990 Verlag GmbH & Co. KGaA, Weinheim