Metal-Free Arylalkylation of N-Aryl Acrylamides with Azobisalkylnitriles

Abstract

A novel metal-free arylalkylation of N-aryl acrylamides with readily available azobisalkylnitriles leading to cyano-containing oxindoles has been developed. The use of readily available azobisalkylnitriles and DTBP as oxidant makes this protocol environmentally benign and practical.

Key words

metal-free - aryalkylation - acrylamide - AIBN - oxindole

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• 16 General Procedure of the Synthesis of Cyano-Containing Oxindoles 2a–t and 3a–f An oven-dried 15 mL screw-capped vial containing 1 (0.2 mmol), AIBN (0.4 mmol), and DTBP (0.3 mmol) were evacuated and purged with Ar gas three times. Then, DCE (2.00 mL) was added via syringe. The reaction mixture was stirred at 80 °C for 16 h. After cooling to r.t., the solvent was evaporated and then the residue was purified on a silica gel column using PE–EtOAc (4:1) as eluent to give the desired product 2 or 3. Three Representative Examples 3-(1,3-Dimethyl-2-oxoindolin-3-yl)-2,2-dimethylpropanenitrile (2a) White solid; mp 118 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.35 (m, 2 H), 7.14 (t, J = 7.5 Hz, 1 H), 6.93 (d, J = 7.7 Hz, 1 H), 3.27 (s, 3 H), 2.35 (d, J = 14.6 Hz, 1 H), 2.19 (d, J = 14.6 Hz, 1 H), 1.38 (s, 3 H), 1.19 (s, 3 H), 1.11 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 179.67, 143.16, 130.93, 128.65, 124.70, 123.97, 122.48, 108.52, 47.01, 46.56, 30.72, 29.70, 27.44, 26.65, 26.39. IR (thin film): ν_max = 3059, 2967, 2936, 2233, 1715, 1609, 1493, 1469, 1377, 1349, 1338, 1136, 1021, 774 cm^–1. HRMS (ESI-TOF): m/z calcd for C₁₅H₁₈N₂NaO⁺: 265.1317 [M + Na]⁺; found: 265.1318. 3-(1-Benzyl-3-methyl-2-oxoindolin-3-yl)-2,2-dimethylpropanenitrile (2b) Clear oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.31 (m, 5 H), 7.30–7.24 (m, 2 H), 7.11 (t, d, J = 7.8 Hz, 1 H), 6.87 (d, J = 7.8 Hz, 1 H), 5.16 (d, J = 15.5 Hz, 1 H), 4.76 (d, J = 15.5 Hz, 1 H), 2.39 (d, J = 14.6 Hz, 1 H), 2.26 (d, J = 14.7 Hz, 1 H), 1.43 (s, 3 H), 1.23 (s, 3 H), 1.06 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 179.75, 142.30, 135.77, 130.87, 128.77, 128.52, 127.69, 127.61, 124.88, 124.17, 122.48, 109.51, 47.05, 46.24, 44.10, 30.80, 29.77, 28.12, 26.36. IR (thin film): ν_max = 2975, 2926, 1708, 1612, 1489, 1468, 1453, 1380, 1357, 1177, 756 cm^–1. HRMS (ESI-TOF): m/z calcd for C₂₁H₂₂N₂NaO⁺: 341.1630 [M + Na]⁺; found: 341.1633. 2-[(1,3-Dimethyl-2-oxoindolin-3-yl)methyl]-2-methylbutanenitrile (3a) White solid; mp 124 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.39–7.30 (m, 2 H), 7.14 (dd, J = 15.7, 7.8 Hz, 1 H), 6.93 (d, J = 7.7 Hz, 1 H), 3.27 (s, 3 H), 2.45 (d, J = 14.6 Hz, 1 H), 2.27 (q, J = 14.7 Hz, 1 H), 2.07 (d, J = 14.6 Hz, 1 H), 1.59–1.53 (m, 1 H), 1.46–1.33 (m, 4 H), 1.04–0.96 (m, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 180.04, 179.52, 143.36, 143.02, 131.47, 130.86, 128.63, 138.56, 124.92, 124.26, 123.28, 122.78, 122.57, 122.27, 108.60, 108.44, 46.94, 46.88, 45.40, 44.46, 35.64, 35.49, 35.30, 33.14, 27.84, 27.59, 26.42, 26.38, 25.82, 22.73, 9.12, 8.98. IR (thin film): ν_max = 2986, 2927, 2235, 1710, 1609, 1494, 1470, 1361, 1349, 1338, 1136, 1021, 769 cm^–1. HRMS (ESI-TOF): m/z calcd for C₁₆H₂₀N₂NaO⁺: 279.1473 [M + Na]⁺; found: 279.1474.