Glycosylidene Carbenes. Part 6. Synthesis of Alkyl and Fluoroalkyl Glycosides

Article abstract of DOI:10.1002/hlca.19920750218

The synthesis of glycosides from the diazirine 1 and a range of alcohols under thermal and/or photolitic conditions are described.Yields and diastereoselectivities depend upon the pK_HA values of the alcohols, the solvent, and the reaction temperature.The glycosidation of weakly acidic alcohols (MeOH, EtOH, i-PrOH, and t-BuOH, 1 equiv. each) in CH2Cl2 at room temperature leads to the glycosides 2-5 in yields between 60 and 34percent (Scheme I and Table 1) At -70 to -60 deg, yields are markedly higher.In CH2Cl2, diastereoselectivities are very low.In THF, at -70 to -60 deg, however, glycosidation of i-PrOH leads to α-D-/β-D-4 in a ratio of 8:92.More strongly acidic alcohols, such as CF3CH2OH, (CF3)2CHOH, and (CF3)2C(Me)OH, and the highly fluorinated long-chain alcohols CF3(CF2)5(CH2)2OH (11) and CHF2(CF2)9CH2OH (13) react (CH2Cl2, r.t.) in yields between 73 and 85percent and lead mainly to the β-D-glucosides β-D-6 to β-D-8, β-D-12, and β-D-14 (d.e. 14-68percent).Yields and diastereoselectivities are markedly improved, when toluene, dioxane, 1,2-dimethoxyethane, or THF are used, as examined for the glycosidation of (CF3)2C(Me)OH, yielding (1,2-dimethoxyethane, 25 deg) 80percent of α-D-/β-D-8 in a ratio of 2:98 (d.e. 96percent; Table 4).In EtCN, (CF3)2C(Me)OH yields up to 55percent of the imidate 10.Glycosidation of di-O-isopropylidene-glucose 15 leads to 16 (CH2Cl2, r.t; 65percent, α-D/β-D=33:67).That glycosidation occurs by initial protonation of the intermediate glycosylidene carbene is evidenced, for strongly acidic alcohols, by the formation of 10, derived from the attack of (CF3)2MeCO(1-) on an intermediate nitrilium ion (Scheme 4), and, for weakly acidic alcohols, by the formation of α-D-9 and β-D-9, derived by attack of i-PrO(1-) on intermediate tetrahydrofuranylium ions.A working hypothesis is presented (Scheme 3).The diastereoselectivities are rationalized on the basis of a protonation in the ? plane of the intermediate carbene, the stabilization of the thereby generated ion pair by interaction with the BnO-C(2) group, with the solvent, and/or with the alcohol, and the final nucleophilic attack by RO(1-) in the ? plane of the (solvated) oxonium ion.