An Alternative Reaction Course in O-Glycosidation with O-Glycosyl Trichloroacetimidates as Glycosyl Donors and Lewis Acidic Metal Salts as Catalyst: Acid-Base Catalysis with Gold Chloride-Glycosyl Acceptor Adducts

摘要

Gold(Ⅲ) chloride as catalyst for O-glycosyl trichlor-oacetimidate activation revealed low affinity to the glycosyl donor but high affinity to the hydroxy group of the acceptor alcohol moiety, thus leading to catalyst-acceptor adduct formation. Charge separation in this adduct, increasing the proton acidity and the oxygen nucleophilicity, permits donor activation and concomitant acceptor transfer in a hydrogen-bond mediated S_N2-type transition state. Hence, the sequential binding between acceptor and catalyst and then with the glycosyl donor enables self-organization of an ordered transition-state. This way, with various acceptors, even at temperatures below -60 ℃, fast and high yielding glycosidations in high anomeric selectivities were recorded, showing the power of this gold(Ⅲ) chloride acid-base catalysis. Alternative reaction courses via hydrogen chloride or HAuCl_4 activation or intermediate generation of glycosyl chloride as the real donor could be excluded. With partially O-protected acceptors, prone to bidentate ligation to gold(Ⅲ) chloride, particularly high reactivities and anomeric selectivities were observed. Gold(Ⅰ) chloride follows the same catalyst-acceptor adduct driven acid-base catalysis reaction course.