Photocatalytic 1,4-Addition of Aromatic Aldehydes or Ketones via Umpoled Carbinol Anions

Abstract

A 1,4-addition reaction of aromatic aldehydes or ketones to electron-deficient olefins was achieved under photocatalytic conditions. In the reaction, an umpoled carbinol anion generated in situ through two successive one-electron reductions of the carbonyl compound reacted nucleophilically with the electron-deficient olefin. Various electron-deficient aromatic aldehydes and ketones successfully underwent the reaction to afford the corresponding γ-functionalized alcohols.

Key words

1,4-addition reaction - carbinol anions - umpolung - photocatalysis - iridium catalysis - alcohols

Publication History

Received: 02 June 2023

Accepted after revision: 04 July 2023

Accepted Manuscript online:
04 July 2023

Article published online:
14 August 2023

• References and Notes


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• 14 Methyl 4-(3-Cyano-1-hydroxy-1-methylpropyl)benzoate (3aA); Typical Procedure Ir(ppy)₂(dtbbpy)PF₆ (1.88 mg, 0.0021 mmol, 1 mol%) and DMBI (134.2 mg, 0.60 mmol, 3 equiv) were placed in a 20 mL Schlenk tube equipped with a stirrer bar. The Schlenk tube was filled with N₂ by vacuum–refill cycles (×3). DMA (4 mL) was added, and CO₂ (5 mL) was bubbled into the solution over 30 s using a syringe pump. A N₂ balloon was attached to the Schlenk tube, and acrylonitrile (2A; 52.7 mg, 1.0 mmol, 5 equiv) was added. By using a syringe pump, a solution methyl 4-acetylbenzoate (1a; 35.9 mg, 0.20 mmol) in DMA (1 mL) was added dropwise over 80 min to the reaction mixture under blue-light irradiation (λ = 448 nm) at 20 °C, and the mixture was stirred for a further 70 min. 2 M aq HCl was added and the resulting mixture was extracted with EtOAc (×3). The combined organic phase was washed with water (×2) and brine, then dried (MgSO₄) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography [silica gel, 20–35% EtOAc–hexane (gradient)] to give a white solid; yield: 35.6 mg (0.15 mmol, 76%). IR (ATR): 3454 (m), 2257 (m), 1719 (s), 1279 (s) cm^–1. ¹H NMR (396 MHz, CDCl₃): δ = 8.03 (d, J = 8.6 Hz, 2 H), 7.49 (d, J = 8.6 Hz, 2 H), 3.92 (s, 3 H), 2.46–2.38 (m, 1 H), 2.18 (t, J = 7.7 Hz, 2 H), 2.10–2.02 (m, 1 H), 1.99 (s, 1 H), 1.64 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 166.9, 150.7, 130.0, 129.3, 124.9, 120.0, 73.7, 52.3, 39.5, 30.7, 12.2. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₁₃H₁₅NNaO₃: 256.0944; found: 256.0951.

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