Characterization of the Isochromen‐4‐yl‐gold(I) Intermediate in the Gold(I)‐Catalyzed Glycosidation of Glycosyl ortho‐Alkynylbenzoates and Enhancement of the Catalytic Efficiency Thereof

Abstract

We have recently developed a new glycosylation protocol with glycosyl ortho-alkynylbenzoates as donors and a gold(I) complex (e.g., [Ph 3 PAuOTf], OTf = O 3 SCF 3 ) as catalyst. [1] The power and versatility of this gold(I)-catalyzed glycosylation method have been demonstrated in the effective construction of a wide variety of glycosidic linkages and the total synthesis of complex oligosaccharides and glycoconjugates. [1][2][3][4][5][6] Moreover, the unprecedented activation mechanism has endowed this protocol with unique merits, including 1) the absence of competitive nucleophilic species (which usually occur in the leaving entity or promoter in classical glycosylation reactions), which enables glycosylation-initiated polymerization of tetrahydrofuran to proceed smoothly; [3] 2) the lack of deteriorative electrophilic species (such as the soft Lewis acidic species used as promoters in classical glycosylation reactions), which enables flavonol 3-OH derivatives vulnerable toward electrophiles to be glycosylated efficiently; [4] and 3) the mild and nearly neutral conditions, which allow the extremely acid-labile aglycones, such as the N-Boc-protected purine derivatives (Boc = tert-butoxycarbonyl) and dammarane derivatives, to be glycosylated effectively. [5,6] This glycosylation protocol has been developed on the basis of mechanistic rational as depicted in Scheme 1. [1b] Activation of the C À C triple bond positioned in the oalkynylbenzoate moiety in donor A with a gold(I) complex (e.g., [Ph 3 PAuOTf]) led to isochromen-4-yl-gold(I) complex D and sugar oxocarbenium ion B. Capture of the putative sugar oxocarbenium species B or related intermediates [7] by the nucleophilic acceptor HNu provided glycoside C. The H + released from HNu then protodeaurated the vinyl gold(I) complex D to give isocoumarin E with regeneration of the active Au I species to complete the catalytic cycle. Activation of a CÀC triple bond with gold(I) species toward nucleophilic attack has been reported for numerous gold(I)-catalyzed transformations. [8] Recently, a few of the proposed vinyl gold(I) intermediates in these transformations were characterized. [9] Herein we report the isolation and characterization of the isochromen-4-yl-gold(I) intermediate D, which has enabled us to gain insight into the detailed catalytic cycle so as to provide a solution to enhance the catalytic efficiency of the gold(I)-catalyzed glycosylation reaction.Unexpected but easily understandable results were obtained when we attempted to glycosylate with 3,4,6-tri-Oacetyl-2-deoxy-2-p-methoxybenzylideneamino-b-d-glucopyranosyl-o-hexynylbenzoate (1) as donor (Scheme 2). [10] Under the normal conditions (0.1 equiv [Ph 3 PAuOTf], toluene, 4 molecular sieves (M.S.), RT), [1] the coupling reaction of donor 1 with n-pentenol (2) was hardly observable; upon raising the loading of the gold(I) catalyst to 0.5 equiv, the reaction proceeded smoothly, albeit leading to the b-glycoside 3 and aglycoside 4 in 37 and 47 % yield, respectively (within 4 h). The a-glycoside 4 was...

Characterization of Vinylgold Intermediates: Gold‐Mediated Cyclization of Acetylenic Amides

“…In most cases, however, the gold‐catalyzed reactions are interpreted with “suggested” mechanisms, as pointed out by Hashmi in a recent review article on the gold intermediates identified by direct observation and characterization 2. So far, a limited number of gold intermediates have been characterized by X‐ray crystallography,3 including several vinylgold(I) species obtained from alkynes3a–f or allenes,3g,h and gem‐digold(I) species from vinylboronic acids through an exchange reaction 3i,j…”

“…So far only a few vinylgold(I) intermediates have been characterized by X‐ray crystallography as mentioned above,3a–f but no of vinylgold(III) species have been characterized yet. Our efforts to obtain single crystals from the reaction mixture resulted in pale yellow prisms, the structure of whcih was resolved to be A by X‐ray diffraction analysis.…”

A Highly Efficient Approach to the Synthesis of Complex α-Glycosyl Phosphosaccharides

“…The straightforward syntheses of extremely unstable diphenyl phosphate 3e' 8 and 3f' demonstrate the utility of this strategy for directly glycosylating weakly nucleophilic phosphoric acid. Moreover, 3f can be obtained on a 1.2 g scale with low catalytic loading of Ph3PAuNTf2 (0.5 mol%) albeit in slightly decreased diastereoselectivity (17/1) and yield (87%) 42 . The deprotected form of 3f might serve as replacement therapy for the disease of congenital disorder of glycosylation type Ia, which is under clinical trial 43 .…”