Light-Mediated Cross-Coupling of Anomeric Trifluoroborates

Abstract

Stereoselective reactions at the anomeric carbon constitute the cornerstone of preparative carbohydrate chemistry. Here, we report stereoselective C-arylation and etherification reactions of anomeric trifluoroborates derived from BMIDA esters. These reactions are characterized by high anomeric selectivities for 2-deoxysugars and broad substrate scope (24 examples), including disaccharides and trifluoroborates with free hydroxyl groups. Taken together, this new class of carbohydrate reagents adds the palette of anomeric nucleophile reagents suitable for efficient installation of C-C bonds.

Scheme 1.. C-Glycosides and Selected Synthetic Methods

Scheme 2.. Transformations of Anomeric MIDA Boronates^a

^aReagents and conditions: (a) KHF₂ (5.0 equiv), MeOH, 70 °C, 18 h; (b) 14 (1.2 equiv), 12h (1.0 equiv), TMSOTf (0.05 equiv), 4 Å MS, CH₂Cl₂, −20 °C, 2 h; (c) 15 (1.2 equiv), 12h (1.0 equiv), NIS (1.2 equiv), AgOTf (0.2 equiv), 4 Å MS, CH₂Cl₂, −45 °C, 2 h; (d) AgOTf (0.10 equiv), Au(PPh₃)Cl (0.10 equiv), 12h (1.0 equiv), 17 (1.5 equiv), 4 A° MS, CH₂Cl₂, −78 to 23 °C, 30 h; (e) 14 (1.2 equiv), 12f (1.0 equiv), TMSOTf (0.05 equiv), 4 Å MS, CH₂Cl₂, −20 °C, 2 h.

Scheme 3.. Scope of C-Arylation^b

^a87% isolated yield with 0.15 mmol of 13a. ^bFor all compounds tested, only one anomer (α: β > 99: 1) was observed by ¹H NMR in crude reaction mixtures. Reagents and conditions taken from Table 1, entry 6. Aryl iodides used for all entries unless stated otherwise.

Scheme 4.. Scope of Photoredox C-Arylation with Pyranosyl Trifluoroborates

Scheme 5.. Scope of Photoredox Etherification of 2-Deoxy-d-glucose Trifluoroborate^a

^aReagents and conditions: (a) 13a (0.15 mmol), 25 (0.10 mmol), PC3 (0.025 equiv), 1,4-dioxane (2.0 mL), 23 °C, 24 h, N₂; (b) 13a (0.10 mmol), 27 (0.10 mmol), PC3 (0.025 equiv), 1,4-dioxane (2.0 mL), 23 °C, 24 h, N₂.