title: 1,2-migration of 2'-oxoalkyl group and concomitant synthesis of 2-C-branched O-, S-glycosides and glycosyl azides via 1,2-cyclopropanated sugars.
abstract: Treatment of 2'-oxoalkyl 2-O-Ms(Ts)-alpha-C-mannosides (4, 5, and 6) with base resulted in 1,2-cyclopropanation via an intramolecular SN2 reaction due to their 1,2-trans-diaxial configurations. The 1,2-cyclopropanated sugars (10 and 13) were reacted with various alcohols, thiols, and sodium azide to produce 2-C-branched O- and S-glycosides and glycosyl azides (11, 14-28) in good to excellent yields. In contrast, 1,2-cis 2'-oxoalkyl 2-O-Ms(Ts)-alpha-C-glucoside 9 formed an acyclic conjugated aldehyde (31) under basic conditions, which occurred by 1'-enolation followed by beta-elimination. An intramolecular Michael addition from 31 produced 2-O-Ms-beta-C-glucoside 30 as a major product. However, due to the electron-withdrawing effect exerted by 2-O-Ms compound 31 also undergoes a C2 epimerization to form 32. Thereafter, the intramolecular Michael addition led to the formation of both 1,2-trans 2'-oxoalkyl 2-O-Ms-alpha-C-mannoside 4 and its beta-anomer (33). Because beta-elimination/Michael addition and C2 epimerization are reversible reactions, equilibriums among 9, 31, 30, 32, 33, and 4 were established, which included the transformation of 1,2-cis C-glucoside 9 into 1,2-trans C-mannoside 4. The subsequent 1,2-cyclopropanation of 4 was an irreversible reaction yielding 1,2-cyclopropanated 10 and further conversion to 1,2-migration products (11 and 12).
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
authors.forename: Huawu
authors.initials: H
authors.lastname: Shao
authors.forename: Sanchai
authors.initials: S
authors.lastname: Ekthawatchai
authors.forename: Chien-Sheng
authors.initials: CS
authors.lastname: Chen
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
mesh_terms: D020650:Combinatorial Chemistry Techniques; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D006027:Glycosides