Reversal of Anomeric Selectivity with O‐Glycosyl Trichloroacetimidates as Glycosyl Donors and Thiols as Acceptors Under Acid/Base Catalysis

Abstract

Boron trifluoride or trimethylsilyl trifluoromethanesulfonate catalysed the generation of thioglycosides from O‐glucopyranosyl or O‐galactopyranosyl trichloroacetimidates and thiols giving mainly or exclusively α‐thioglycosides. However, the same reactions with phenylboron difluoride as catalyst are highly β‐selective. An SN2‐type reaction course under acid/base catalysis is invoked by these and previous results.

Cooperative Catalysis in Glycosidation Reactions with O‐Glycosyl Trichloroacetimidates as Glycosyl Donors

“…[21] Upon interaction with donor 1a, this complex generates activation complex A, leading to proton transfer to the leaving group in an intramolecular reaction and concomitant proton release from the acceptor, thus facilitating an acid-base catalyzed S N 2-type glycoside bond formation. [22] Thus, thiourea 4 functions as a relay for proton transfer as, for instance, often found for the imidazole residue in the active site of hydrolases. Competing reaction courses, leading for example to a-product formation via directed attack at the trichloroacetimidate favoring an S N 1-type reaction course (or reaction between donor and catalyst), are only effective in the presence of less reactive acceptors.…”

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art

“…87 Substituting thiols for alcohols in this process gives rise to thioglycosides with inversion of configuration. 88 The use of binol-based chiral phosphoric acids as promoters for glycosylations with trichloroacetimidate-type donors enables enantioselectivity in couplings to racemic acceptors. A twelve-membered cyclic transition state is invoked in which the phosphoric acid hydrogen simultaneously bonds to the donor and acceptor and preorganizes the latter for an S N 2-type displacement.…”

Stereospecific, Pyrylium Salt-Catalyzed O-Glycosylations of Phenols and Alkyl Alcohols

“…One of the major advantages of using trichloroacetimidates is the selective accessibility of either their α-or β-anomers, which has previously been utilized by Schmidt [26][27][28][57][58][59] and ourselves. 37 To investigate whether the pyrylium-catalysts also engaged in similar stereospecific glycosylations, we carried out a series of glucosylations and galactosylations (Scheme 4, top and middle) using the corresponding β-trichloroacetimidates.…”

“…Alternatively, catalytic glycosylations can be accomplished by activation of the nucleophile (Figure 1, bottom). This particular method was pioneered by Schmidt using various reagents to form a catalyst-nucleophile complex capable of activating a trichloroacetimidate electrophile, [23][24][25][26][27][28] resulting in inversion of the anomeric configuration of the electrophile. In recent years, related methods relying on activated nucleophile-catalyst-electrophile intermediates have been developed by Taylor, [29][30][31] Toshima 32 and Jacobsen, [33][34][35][36] resulting in stereospecific glycosylations.…”