Cross-Electrophile Coupling of 2-Iodoglycals Enables Efficient Access to 2-C-Glycals

Abstract

A general strategy was developed for synthesizing 2-C-glycals through a nickel-catalyzed cross-electrophile coupling reaction of 2-iodoglycals with (hetero)aryl iodides. Key to the success of this methodology is the use of an electron-deficient bipyridyl ligand. This innovative approach facilitates the efficient construction of 2-C-glycals, thereby broadening the synthetic repertoire available for glycochemistry.

Key words

cross-electrophile coupling - glycals - nickel catalysis - iodoglycals - C–C coupling

• References and Notes

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• 25 Cross-Electrophilic Coupling of 2-Iodoglycals; General Procedure A one-dram vial equipped with a screw-top septum was charged with the appropriate 2-iodoglycal (1.00 equiv), electrophilic reagent (3.00 equiv), NiBr₂-dme (10.0 mol%), L2 (20.0 mol%), TBAI (0.150 mmol), and Zn (0.400 mmol). The vial was then evacuated and refilled with N₂ (3×). Anhyd 1,4-dioxane (1.00 mL) was added, and the mixture was stirred at 50 °C for 24 h, then cooled to r.t. and concentrated. The crude product was purified by column chromatography (silica gel). Product 8a: Prepared by the general method and purified by column chromatography [silica gel, PE–EtOAc (10:1)] as a colorless oil; yield: 42.5 mg (74%). ¹H NMR (500 MHz, CDCl₃): δ = 7.60 (d, J = 7.6 Hz, 2 H), 7.53 (s, 2 H), 7.44 (m, 2 H), 7.35–7.34 (m, 12 H), 7.27–7.21 (m, 4 H), 7.05 (d, J = 5.8 Hz, 2 H), 6.92 (s, 1 H), 4.77–4.69 (m, 2 H), 4.48–4.40 (m, 3 H), 4.44 (d, J = 13.1 Hz, 3 H), 4.12–4.07 (m, 1 H), 3.93–3.85 (m, 1 H), 3.75 (dd, J = 10.6, 3.3 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 143.1, 141.0, 139.2, 138.1 (2 C), 137.9, 136.5, 128.9 (2 C), 128.7, 128.5, 128.4, 128.2, 128.1, 127.9, 127.8, 127.2 (2 C), 127.0, 126.3, 112.9, 75.9, 73.6, 73.3, 72.4, 72.0, 70.6, 68.4. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₉H₃₆NaO₄: 591.2511; found: 591.2510.