C–H Alkylation of Heteroarenes with Alkyl Oxalates by Molecular Photoelectrocatalysis

Dedicated to Professor Ilhyong Ryu on the occasion of his 70^th birthday.

Abstract

An oxidant- and metal-free photoelectrocatalytic C–H alkylation reaction of heteroarenes with alkyl oxalates has been developed. Several classes of heteroaromatics, such as quinolines, isoquinolines, pyridines, and phenanthridines, can be alkylated with tertiary or secondary alkyl oxalates. The photoelectrochemical synthesis employs 2,4,5,6-tetra-9H-carbazol-9-ylisophthalonitrile as a molecular catalyst and allows the oxidative transformations to proceed through evolution of hydrogen without a sacrificial chemical oxidant.

Key words

photoelectrochemistry - photoelectrocatalysis - C–H functionalization - alkyl oxalates - heterocycles

Publication History

Received: 23 September 2020

Accepted after revision: 23 October 2020

Accepted Manuscript online:
23 October 2020

Article published online:
23 November 2020

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• 15 Photoelectrochemical Alkylation of Hetarenes; General Procedure A 10 mL Schlenk tube equipped with a magnetic stirrer bar was charged with the appropriate hetarene (0.2 mmol, 1.0 equiv) and oxalate (0.6 mmol, 3.0 equiv), together with 4CzIPN (0.002 mmol, 1 mol%), Et₄NPF₆ (0.04 mmol, 0.2 equiv), and MeCN (6 mL). The Schlenk tube was equipped with a reticulated vitreous carbon (100 PPI) anode (0.5 × 1.5 × 1.2 cm) and a platinum plate (1 × 1 cm) cathode. The reaction mixture was bubbled with argon for 15 min and then TFA (0.2 mmol, 1 equiv) was added. LEDs (λ = 455 nm, 20 W) were placed 2 cm to the side of the reactor, and the reaction was carried out with a constant current of 2 mA at about 50 °C (internal temperature) until the substrate was completely consumed (TLC or ¹H NMR). The reaction was then quenched with sat. aq NaHCO₃, and the aqueous layer was extracted with EtOAc (3 × 10 mL). The organic extracts were combined and concentrated under reduced pressure. The residue was purified by chromatography (silica gel, EtOAc–hexanes).
• 16 2-Cyclohexyl-4-methylquinoline (3) Colorless oil; yield: 34 mg (76%). ¹H NMR (600 MHz, CDCl₃): δ = 8.07 (d, J = 8.3 Hz, 1 H), 7.95 (d, J = 8.1 Hz, 1 H), 7.74–7.65 (m, 1 H), 7.57–7.46 (m, 1 H), 7.18 (s, 1 H), 2.90 (td, J = 12.1, 3.4 Hz, 1 H), 2.69 (s, 3 H), 2.08–2.01 (m, 2 H), 1.95–1.88 (m, 2 H), 1.84–1.78 (m, 1 H), 1.70–1.61 (m, 2 H), 1.53–1.44 (m, 2 H), 1.40–1.33 (m, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 166.6, 147.7, 144.4, 129.6, 129.0, 127.1, 125.5, 123.7, 120.4, 47.7, 32.9, 26.7, 26.2, 19.0.
• 17 2,9-Diisopropyl-4,7-dimethyl-1,10-phenanthroline (20) Light-yellow solid; yield: 39 mg (67%); mp 129.8–130.3 °C. 1H NMR (500 MHz, CDCl3): δ = 7.91 (s, 2 H), 7.37 (s, 2 H), 3.52 (hept, J = 6.9 Hz, 2 H), 2.74 (s, 6 H), 1.47 (d, J = 7.0 Hz, 12 H). 13C NMR (126 MHz, CDCl3): δ = 167.4, 145.4, 144.2, 126.7, 121.1, 121.0, 37.3, 23.0, 19.5.
• 18 4-Cyclohexyl-2,6-dimethylpyridine (21) Colorless oil; yield: 17 mg (45%); 1H NMR (600 MHz, CDCl3): δ = 6.81 (s, 2 H), 2.51 (s, 6 H), 2.43 (tt, J = 12.0, 4.8 Hz, 1 H), 1.92–1.73 (m, 6 H), 1.48–1.35 (m, 4 H). 13C NMR (151 MHz, CDCl3): δ = 157.6, 157.4, 119.1, 44.0, 33.7, 26.8, 26.2, 24.6.