Photoinduced 1,2-Hydro(cyanomethylation) of Alkenes with a Cyanomethylphosphonium Ylide

Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

An efficient method has been developed for the 1,2-hydro(cyanomethylation) of alkenes, in which a cyanomethyl radical species is generated from a cyanomethylphosphonium ylide by irradiation with visible light in the presence of an iridium complex, a thiol, and ascorbic acid. The cyanomethyl radical species then adds across the C=C double bond of an alkene to form an elongated alkyl radical species that accepts a hydrogen atom from the thiol to produce an elongated aliphatic nitrile. The ascorbic acid acts as the reductant to complete the catalytic cycle.

Key words

alkenes - nitriles - photocatalysis - radicals - phosphonium ylides - hydro(cyanomethylation)

• References and Notes


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• 16 The reactions of terminal alkynes such as 4-phenylbut-1-yne gave complex mixtures of products, in which the corresponding 1,2-hydro(cyanomethylation) product (a β,γ-unsaturated nitrile) was present in ~10% yield as a 1:1 mixture of E- and Z-isomers.
• 17 6-Phenylhexanenitrile (3a); Typical Procedure A vial (2–5 mL; Biotage, Fisher Scientific) equipped with a stirrer bar was charged with the phosphorus ylide 2 (302 mg, 1.00 mmol), fac-Ir(ppy)₃ (3.30 mg, 0.005 mmol, 1.0 mol%), ascorbic acid (882 mg, 5.00 mmol), and KHSO₄ (207 mg, 1.52 mmol). The vial was then flushed with argon gas and quickly capped with a Teflon septum. 4-Phenylbut-1-ene (1a, 67.6 mg, 0.51 mmol), C₆F₅SH (20.0 mg, 0.100 mmol, 20 mol%), distilled CH₃CN (2.5 mL), and H₂O (2.5 mL; degassed with argon gas for 30 min) were added from a syringe, and the mixture was stirred vigorously for 40 h under blue LED lights (470 nm, 23 W) while the vial was cooled with a fan. The mixture was then diluted with brine (25 mL) and extracted with CH₂Cl₂ (3 × 25 mL). The organic phase was dried (Na₂SO₄), filtered, and concentrated under reduced pressure to give a residue that was purified by column chromatography [silica gel, hexane/EtOAc (9:1)] to give a colorless oil; yield: 70.7 mg (0.41 mmol, 80%). IR (ATR): 2936, 2245, 1454 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.45–1.53 (m, 2 H), 1.63–1.73 (m, 4 H), 2.33 (t, J = 7.2 Hz, 2 H), 2.63 (t, J = 7.6 Hz, 2 H), 7.16–7.21 (m, 3 H), 7.26–7.31 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.1, 25.3, 28.3, 30.5, 35.5, 119.7, 125.8, 128.3, 141.9. HRMS (EI⁺): m/z [M]⁺ calcd for C₁₂H₁₅N: 173.1204; found: 173.1205.