Copper-Catalyzed Alkynylation of Benzylic C–H Bonds with Alkynylboronic Esters

Abstract

We report a simple method for copper-catalyzed benzylic C–H alkynylation that uses alkynylboronic esters as nucleophilic coupling partners. The catalytic system is readily available and the reaction takes place under mild conditions. Different substrates for the C–H functionalization, as well as various alkynylboronic ester nucleophiles, were evaluated. Finally, three examples of enantioselective C–H alkynylations are presented.

Key words

C–H functionalization - copper catalysis - alkynylation - boronic esters - homogeneous catalysis

• References and Notes

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• 10 Trimethyl[3-(1-naphthyl)but-1-yn-1-yl]silane (4a); Typical Procedure In an argon-filled glovebox, a 4 mL vial was charged with CuOAc (1.2 mg, 0.010 mmol; 5 mol%), dtbbpy (3.2 mg, 0.012 mmol; 6 mol%), and Li₂CO₃ (29.6 mg, 0.400 mmol; 2.00 equiv). Benzene (1.6 mL) [CAUTION: carcinogen] was added followed by DMA (0.4 mL), and the mixture was stirred for 30 min. Then, 1-ethylnaphthalene (2a) (31.0 μL, 0.200 mmol; 1.00 equiv) and alkynylboronic ester 3a (62.8 mg, 0.280 mmol; 1.40 equiv) were added, and the mixture was stirred. After one minute, NFSI (126.1 mg, 0.400 mmol; 2.00 equiv) was added with stirring. The vial was sealed with a Teflon-lined screw cap and removed from the glovebox. Outside the glovebox, the mixture was stirred in an aluminum block at 30 °C for 16 h. The reaction was then quenched by filtration through silica gel with pentane and the mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, pentane) to give a colorless oil; yield: 32 mg (63%). ¹H NMR (400 MHz, CDCl₃): δ = 8.12 (d, J = 8.3 Hz, 1 H), 7.89 (dd, J = 7.9, 1.6 Hz, 1 H), 7.78 (d, J = 7.7 Hz, 2 H), 7.62–7.45 (m, 3 H), 4.57 (q, J = 7.1 Hz, 1 H), 1.66 (d, J = 7.1 Hz, 3 H), 0.22 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 138.7, 133.9, 130.5, 128.9, 127.4, 125.9, 125.7, 125.5, 124.3, 123.1, 109.7, 86.6, 29.5, 23.6, 0.2 (3 C). MS (EI): m/z [M ^∙+] calcd for C₁₇H₂₀Si: 252; found: 252.
• 11 The absolute configuration of (R)-4a was determined by comparison of peak orders in chiral HPLC with those reported by Liu and co-workers (ref. 7), as well as by comparison of the optical rotation after TMS deprotection with the value reported in ref. 7.