Copper‐Catalyzed Stereoselective Borylation and Palladium‐Catalyzed Stereospecific Cross‐Coupling to Give Aryl C‐Glycosides

Abstract

Metabolically stable C‐glycosides are an essential family of compounds in bioactive natural products, therapeutic agents, and biological probes. For their application, development of synthetic methods by connecting glycosides and aglycons with strict stereocontrol at the anomeric carbon, as well as with high functional‐group compatibility and environmental compatibility is a pivotal issue. Although Suzuki–Miyaura‐type C(sp3)−C(sp2) cross‐coupling using glycosyl boronates is a potential candidate for the construction of C‐glycosides, neither the cross‐coupling itself nor the facile synthesis of the coupling precursor, glycosyl boronates, have been achieved to date. Herein, it was succeeded to develop a copper‐catalyzed stereoselective one‐step borylation of glycosyl bromides to glycosyl boronates and palladium‐catalyzed stereospecific cross‐coupling of β‐glycosyl borates with aryl bromides to give aryl β‐C‐glycosides, in which the β‐configuration of the anomeric carbon of the glycosyl trifluoroborates is stereoretentively transferred to that of the resulting aryl C‐glycosides.

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

“…Recently, the Higashibayashi group developed a coppercatalyzed stereoselective borylation to access -glycosyl trifluoroborates (Scheme 12B). 45 They utilized a series of glycosyl boronates as coupling partners in a stereospecific cross-coupling. In the process, the stereochemical informa-…”

“…Recently, the Higashibayashi group developed a copper-catalyzed stereoselective borylation to access β-glycosyl trifluoroborates (Scheme 12 B). 45 They utilized a series of β-glycosyl boronates as coupling partners in a stereospecific cross-coupling. In the process, the stereochemical information on the anomeric carbon was delivered to the desired coupling products in a stereoretentive manner without the formation of any α-C-glycosides.…”

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.…”

“…23 We then envisioned a β-selective C-glycosylation from β-glycosyl boronate 4 , the precursor of 1 , because 4 should be a useful common intermediate for α- and β-C-glycosides. Although the application of a Suzuki–Miyaura cross-coupling would be a standard approach, 24 we decided to examine the stereoretentive construction of β-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-β-C-glycoside analogues from boronate 4 through 1,2-migration, followed by cross-metathesis and hydrogenation of 6 .…”