Stereoselective gem-C,B-Glycosylation via 1,2-Boronate Migration

Abstract

A novel protocol is established for the long-standing challenge of stereoselective geminal bisglycosylations of saccharides. The merger of PPh 3 as a traceless glycosidic leaving group and 1,2-boronate migration enables the simultaneous introduction of C−C and C−B bonds at the anomeric stereogenic center of furanoses and pyranoses. The power of this method is showcased by a set of site-selective modifications of glycosylation products for the construction of bioactive conjugates and skeletons. A scarce metal-free 1,1-difunctionalization process of alkenes is also concomitantly demonstrated.

Phosphorus(III)-Promoted 1,2-Boronate Migration and Application to Stereoselective gem-C,B-Glycosylation

“…In conclusion, an unprecedented stereoselective C,B-glycosylation reaction through a PPh 3 -promoted 1,2-boronate migration has been recently developed by our group. 13 This protocol permits the introduction of both C-C and C-B bonds at an anomeric carbon center with high efficiency and selectivity, a transformation previously unattainable by known methods. DFT calculations provided a preliminary understanding of the mechanism of the process and the origin of stereocontrol.…”

“…10,11 We envisioned that the application of such a strategy to saccharides might provide a novel route for 1,1-difunctionalization at the anomeric carbon position. 13 First, the simple pyran-2-ol derivatives 1 and benzyl pinacol boronate (2a) were adopted in a proof-of-concept demonstration (Scheme 1b). After a set of evaluations, only the phosphonium ylide derivative 1a displayed reactivity, and gave the product in 80% yield.…”

Transition-Metal-Free β-Selective C-Glycosylation of β-Glycosyl Boronates via Stereoretentive 1,2-Migration

“…would be a standard approach, 24 we decided to examine the stereoretentive construction of -C-glycosides through a 1,2-migration of the borate intermediate 5, 25,26 taking advantage of the characteristic reactivity of boronic acid species. Here, we report the synthesis of 2-deoxy--C-glycoside analogues from boronate 4 through 1,2-migration, followed by cross-metathesis and hydrogenation of 6.…”

Development of α-Selective Glycosylation with l-Oleandral and Its Application to the Total Synthesis of Oleandrin

“…To our surprise, despite the widespread applications of catalytic HBr·PPh 3 for the formation of 2-deoxyglycosides, very little information can be found on the use of the alternative phosphonium salts. It is, however, known that the reaction of such salts with dihydropyrans may lead to the formation of the anomeric phosphonium salts …”

“…These results suggest that the basicity of the arylphosphine does not play a significant role; however, the nature of the acid may play a significant impact on both the reactivity and selectivity of this reaction. While HBr·PPh 3 and HBF 4 ·PPh 3 salts are known to provide anomeric phosphonium salts such as 17 (Scheme ), the lack of dependence on the basicity of phosphine is not completely consistent with 17 reacting directly to provide 12 or 13 . These results are more consistent with a complex mechanistic scenario involving multiple reactive species 17 – 18 or covalent variants of 18 such as glycosyl bromides or sulfonates, the distribution and reactivity of which are dependent on the counterion.…”