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

Abstract

Gold(III) chloride as catalyst for O-glycosyl trichloroacetimidate 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(N)2-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 °C, 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 HAuCl4 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.

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

“…It is pleasing to note that on reaction with partially protected acceptor 22 with glycosyl donors 1α and 7α under the optimized conditions lead to the regioisomeric products 23 and 24 [46–47] in moderate yields with good selectivity (Scheme 2). …”

Total Synthesis and Biological Evaluation of the Glycosylated Macrocyclic Antibiotic Mangrolide A

“…Next, we set out to investigate the β‐selective glycosylation with the separately synthesized epoxy alcohol 6 (Scheme ). Various glycosyl donors and activation conditions were examined without success (glycosylfluoride, thioglycoside, phosphoramidate, phosphite ester, trichloroacetimidate,). Extensive experimentation revealed that the combination of 14 and Ph 3 CB(C 6 F 5 ) 4 in a n PrCN/CH 2 Cl 2 mixture resulted in the disaccharide β‐ 15 in 81 % yield with 4.3 to 1 selectivity in favor of the β diastereoisomer.…”

Chemical O‐Glycosylations: An Overview

“…Notably, in this case, high β‐ stereoselectivity was obtained. Recently, further investigation into gold catalysts by Peng and Schmidt has demonstrated the successful synthesis of glycosides with trichloroacetimidate donors via an intramolecular dual catalysis pathway, where AuCl 3 acted as an initiator for the formation of catalyst–acceptor adducts. Interestingly, they obtained high β ‐stereoselective products even with the use of armed glycoside donors.…”