GLYCOSYLIDENE CARBENES .15. SYNTHESIS OF DISACCHARIDES FROM ALLOPYRANOSE-DERIVED VICINAL 1,2-DIOLS - EVIDENCE FOR THE PROTONATION BY A H-BONDED HYDROXY GROUP IN THE DELTA-PLANE OF THE INTERMEDIATE CARBENE, FOLLOWED BY ATTACK ON THE OXYCARBENIUM ION IN THE PI-PLANE

The alpha-D-allo-diol 9 possesses an intramolecular H-bond (HO-C(3) to O-C(1)) in solution and in the solid state (Fig. 2). In solution, it exists as a mixture of the tautomers 9a and 9b (Fig. 3), which possess a bifurcated H-bond, connecting HO-C(2) with both O-C(I) and O-C(3). In addition, 9a possesses the same intramolecular H-bond as in the solid state, while 9b is characterized by an intramolecular H-bond between HO-C(3) and O-C(4). In solution, the beta-D-anomer it is also a mixture of tautomers, 12a and presumably a dimer. The H-bonding in 9 and 12 is evidenced by their IR and H-1-NMR spectra and by a comparison with those of 3-8, 10, and 11. The expected regioselectivity of glycosidation of 9 and 12 by the diazirine 1 or the trichloroacetimidate 2 is discussed on the basis of the relative degree of acidity/nucleophilicity of individual OH groups, as governed by H-bonding. Additional factors determining the regioselectivity of glycosidation by 1 are the direction of carbene approach/proton transfer by H-bonded OH groups, and the stereoelectronic control of both the proton transfer to the alkoxy-alkyl carbene (in the sigma-plane) and the combination of the thereby formed ions (pi-plane of the oxycarbenium ion). Glycosidation of 9 by the diazirine 1 or the trichloroacetimidate 2 proceeded in good yields (75-94%) and with high regioselectivity. Glycosidation of 9 and 12 by 1 or 2 gave mixtures of the disaccharides 14-17 and 18-21, respectively (Scheme 2). As expected, glycosidation of 12 by 1 or by 2 gave a nearly 1:1 mixture of regioisomers and a slight preference for the beta-D-anomers (Table 4). Glycosidation of the alpha-D-anomer 9 gave mostly the 1,3-linked disaccharides 16 and 17 (alpha-D > beta-D) along with the 1,2-linked disaccharides 14 and 15 (alpha-D < beta-D, 1,2-/1,3-linked glycosides ca. 1:4), except in THF and at low temperature, where the beta-D-configurated 1,2-linked disaccharride 15 is predominantly formed. Similarly, glycosidation of 9 with 2 yielded mainly the 1,3-linked disaccharides (1,2-/1,3-linked products ca. 1:3 and alpha-D/beta-D ca. 1:4). Yields and selectivity depend upon the solvent and the temperature. The regioselectivity and the unexpected stereoselectivity of the glycosidation of 9 by 1 evidences the combined effect of the above mentioned factors, which also explain the lack of regio-complementarity in the glycosidation of 9 by 1 and by 2 (Scheme 3). THF solvates the intermediate oxycarbenium ion, as evidenced by the strong influence of this solvent on the regio- and stereoselectivity, particularly at low temperatures, where kinetic control leads to a stereoelectronically preferred axial attack of THF on the oxycarbenium ion.