Iminyl-Radical-Mediated Cyanoalkylarylation of Activated Alkenes Enabled by Silver-Catalyzed Decarboxylation of α-Imino Oxy Acids

Abstract

An iminyl-radical-mediated cyanoalkylarylation of α,β-unsaturated imides with cyclic α-imino oxy acids leading to isoquinoline-1,3(2H,4H)-dione derivatives has been developed. The procedure involves the generation of iminyl radicals through silver-catalyzed oxidative decarboxylation, followed by a C–C bond cleavage, cyanoalkylation, and C–H-functionalization cascade.

Key words

cyanoalkylarylation - imino oxy acids - silver catalysis - oxidative decarboxylation - isoquinolinediones

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• 10 Isoquinolinediones 3a–s; General Procedure The appropriate N-methacryloylbenzamide 1 (0.2 mmol, 1.0 equiv), AgNO₃ (6.7 mg, 20 mol%), K₂S₂O₈ (0.6 mmol, 3.0 equiv), and oxime 2 (0.6 mmol, 3.0 equiv) were added to an oven-dried Schlenk tube. The tube was evacuated and backfilled with argon three times, and then MeCN (2.0 mL) was injected into the tube from a syringe. The mixture was stirred at 90 °C (block heater) for 20 h. The resulting mixture was diluted with EtOAc, and the organic phase was washed successively with H₂O (×3) and brine (×1) then dried (Na₂SO₄) and concentrated in vacuo. The residue was purified by column chromatography [silica gel, EtOAc–PE (gradient 1:10 to 1:4)]. 5-(2,4-Dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-4-yl)pentanenitrile (3a) Pale-yellow oil; yield: 44.1 mg (82%); R_f  = 0.32 (EtOAc–PE, 1:4). ¹H NMR (500 MHz, CDCl₃): δ = 8.25 (dd, J = 8.0, 1.3 Hz, 1 H), 7.68–7.64 (m, 1 H), 7.47–7.40 (m, 2 H), 3.39 (s, 3 H), 2.36–2.30 (m, 1 H), 2.22–2.17 (m, 2 H), 1.93–1.89 (m, 1 H), 1.61 (s, 3 H), 1.55–1.51 (m, 2 H), 1.05–1.02 (m, 1 H), 0.94–0.92 (m, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 176.3, 164.2, 143.0, 134.2, 129.0, 127.5, 125.0, 124.8, 119.1, 47.5, 41.6, 29.7, 27.1, 25.2, 24.4, 16.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉N₂O₂ ⁺: 271.1441; found: 271.1446.
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