Boronic-Acid-Catalyzed Regioselective and 1,2-cis-Stereoselective Glycosylation of Unprotected Sugar Acceptors via S_Ni-Type Mechanism

Abstract

Regio- and 1,2- cis-stereoselective chemical glycosylation of unprotected glycosyl acceptors has been in great demand for the efficient synthesis of natural glycosides. However, simultaneously regulating these selectivities has been a longstanding problem in synthetic organic chemistry. In nature, glycosyl transferases catalyze regioselective 1,2- cis-glycosylations via the Si mechanism, yet no useful chemical glycosylations based on this mechanism have been developed. In this paper, we report a highly regio- and 1,2- cis-stereoselective Si-type glycosylation of 1,2-anhydro donors and unprotected sugar acceptors using p-nitrophenylboronic acid (10e) as a catalyst in the presence of water under mild conditions. Highly controlled regio- and 1,2- cis-stereoselectivities were achieved via the combination of boron-mediated carbohydrate recognition and the Si-type mechanism. Mechanistic studies using the KIEs and DFT calculations were consistent with a highly dissociative concerted Si mechanism. This glycosylation method was applied successfully to the direct glycosylation of unprotected natural glycosides and the efficient synthesis of a complex oligosaccharide with minimal protecting groups.

Stereospecific β‐l‐Rhamnopyranosylation through an SNi‐Type Mechanism by Using Organoboron Reagents

“…In the case of glycoside hydrolyses and glycosylation reactions,the 13 CKIEs for S N 1and dissociative S N 2r eactions are around 1.00 and 1.03, respectively. [9,15,16] Forthe present glycosylation, the experimental 13 C KIE at the anomeric carbon was 1.0034(51) (Table S1), which indicates that this glycosylation also can be regarded as either an S N i-type reaction, ac oncerted S N ir eaction with an exploded transition state,o ra nS N 1r eaction with an extremely short-lived intermediate. [9,15,16] Forthe present glycosylation, the experimental 13 C KIE at the anomeric carbon was 1.0034(51) (Table S1), which indicates that this glycosylation also can be regarded as either an S N i-type reaction, ac oncerted S N ir eaction with an exploded transition state,o ra nS N 1r eaction with an extremely short-lived intermediate.…”

Glycosylation on Unprotected or Partially Protected Acceptors

“…Recently, Takahashi reported highly regio‐ and 1,2‐ cis stereoselective S N i‐type glycosylation (Scheme ) of 1,2‐anhydro donors on unprotected sugar acceptors by using p ‐nitrophenylboronic acid as a catalyst in the presence of water under mild conditions. Highly controlled regio‐ and 1,2‐ cis glycosides were achieved via the combination of the boron‐mediated carbohydrate recognition and S N i‐type mechanism.…”

Gold-catalyzed synthesis of α-D-glucosides using an o-ethynylphenyl β-D-1-thioglucoside donor

“…[1, 2] Glycosylation reactions often involve oxocarbenium intermediates, which frequently result in the formation of anomeric mixtures of low to moderate selectivities (Scheme 1a). Previous achievements in selective construction of 1,2- cis glycosidic bond entail employing donor directing groups,[3–9] harnessing different reactivities of equilibrating donor anomers,[10–12] or exploiting conformational preferences of the reactive intermediates to minimize the formation of undesirable anomers (Scheme 1b). [13–16] Notwithstanding, these methods still rely on specific structural features of the donor molecule and, therefore, often fall short in generality.…”