Triflic Imide‐Catalyzed Glycosylation of Disarmed Glycosyl ortho‐Isopropenylphenylacetates and ortho‐Isopropenylbenzyl Thioglycosides

Abstract

Glycosylation reaction involving the coupling of a glycosyl donor with a glycosyl acceptor is one of the cornerstones of chemical preparation of pure glycans and glycoconjugates of biological relevance. Catalytic glycosylation of glycosyl ester donors and thioglycosides is an attractive but underexplored topic in carbohydrate chemistry. Herein, triflic imide (Tf 2 NH)catalyzed glycosylation of various O-, S-, and C-nucleophiles has been achieved using disarmed glycosyl ortho-isopropenylphenylacetates (GIPPAs) and ortho-isopropenylbenzyl thioglycosides as glycosylating agents. The reactions proceed under mild conditions to give the desired glycosides in good-to-excellent yields. Of particular note, the comparable reactivity for the αisomers and the β-ones of GIPPAs is observed. The mechanistic investigation demonstrates that the isopropenyl group is essential for the reaction and its preferential protonation triggers the reaction. This work provides another member to the arsenals of glycosyl ester and thioglycoside donors suitable for acid-catalyzed glycosylation to create various glycosidic bonds.

Glycosyl o-[1-(p-MeO-Phenyl)vinyl]benzoates (PMPVB) as Easily Accessible, Stable, and Reactive Glycosyl Donors for O-, S-, and C-Glycosylations under Brønsted Acid Catalysis

“…Glycosylation of 2d (46.6 mg, 0.06 mmol) with 3c (59 mg, 0.12 mmol) according to General Procedure 3 afforded 4f (51.2 mg, 84%, 1:1 α:β) as a colorless syrup. The crude product was purified through flash column chromatography: R f = 0.37 (4:1 hexane/EtOAc, v/v); 1 27 (m, 3H), 4.21 (dd, J = 7.9, 1.6 Hz, 1H), 4.12 (dd, J = 10.6, 3.6 Hz, 1H), 4.09−3.98 (m, 6H), 3.95 (dd, J = 10.0, 2.7 Hz, 1H), 3.88 (d, J = 2.5 Hz, 1H), 3.82 (dd, J = 9.7, 7.9 Hz, 1H), 3.77 (dd, J = 10.2, 3.8 Hz, 1H), 3.73 (dd, J = 10.6, 7.2 Hz, 1H), 3.69 (dd, J = 10.6, 7.4 Hz, 1H), 3.61−3.54 (m, 4H), 3.54−3.48 (m, 4H), 1.51 (s, 3H), 1.48 (s, 4H), 1.43 (s, 3H), 1.42 (s, 3H), 1.32 (s, 3H), 1.31−1.28 (d, J = 3.6 Hz, 10H); 13 ). Methyl 4-O-Benzyl-2,3-di-p-methyl-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl)-α-D-galactopyranoside (4k).…”

“…20,21 Though modified NPGs were developed, 22−26 they still require stoichiometric halonium ion activation and a catalytic version is yet to be developed. 27 activatable donors but also cannot be used for all kinds of glycosylations, particularly for the synthesis of S-linked glycosides that might react with the promoter. S-Linked glycosides 12 are biologically important as members of this class of compounds are resistant to enzymatic hydrolysis and can retain the biological properties of glycans.…”

“…The stable alkynyl glycosides initially introduced by Hotha et al , and improved by Yu have found great utility in carbohydrate chemistry and attracted a great deal of attention despite the requirement of expensive metal salts and ligands for their activation. Akin to thioglycosides, one of the major drawbacks of the classic Fraser-Reid’s stable and flexible n -pentenyl glycosides (NPGs) is the requirement of stoichiometric or larger amounts of the strongly electrophilic NIS reagent, in addition to being relatively less reactive. , Though modified NPGs were developed, − they still require stoichiometric halonium ion activation and a catalytic version is yet to be developed . Also, these donors not only are not catalytically activatable donors but also cannot be used for all kinds of glycosylations, particularly for the synthesis of S-linked glycosides that might react with the promoter.…”

S-o-(p-Methoxyphenylethynyl)benzyl (SMPEB) Glycosides for Catalytic Glycosylation and Their Application in the Synthesis of Polyporus Umbellatus Polysaccharides

“…Au(I)-or Cu(II)-catalyzed glycosylation with thioglycosides as donors has been independently reported by Yu, 10 Zhu, 11 Zhang, 12 and Sun. 13 In regard to the metal-free catalytic glycosylation, Ragains 14 and Li 15 have respectively demonstrated that the glycosylation can be realized in the presence of Bronsted acids. Although breakthroughs have been achieved in catalytic activation of thioglycosides, the development of an efficient and catalytic glycosylation is still highly in demand with a readily accessible and easy-to-handle thioglycoside donor, especially a thioglycoside donor that can be catalyzed under metal-free conditions and enable effective glycosylation with a broad substrate scope.…”

Metal-Free Synthesis of Acyl Glycosides and Application to Oligosaccharide Synthesis

“…As shown in Scheme , thioglycoside 1f , a monosaccharide, was converted into β-acyl glycoside 2p , the formation of which was confirmed by TLC. The reaction with thioglycoside-derived glycosyl acceptor 3a was performed with the addition of an equivalent amount of BF 3 ·Et 2 O or TMSOTf, − which is used as the activator of glycosyl esters; however, only low yields of the disaccharide were obtained. The yield improved substantially using a catalytic amount of tris­(pentafluorophenyl)­borane [B­(C 6 F 5 ) 3 ] as a Lewis acid, , which has been recently used in glycosylation as an activator of glycosyl acceptors.…”