Synlett 2010(4): 610-614  
DOI: 10.1055/s-0029-1219151
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Copper(I) Halide Mediated Tandem 1,4-Aryl Migration-Oxidative Amidyl Radical Cyclisation of Bromosulfonamides

Andrew J. Clark*, David R. Fullaway, Nicholas P. Murphy, Hemal Parekh
Department of Chemistry, University of Warwick, Coventry, West Midlands, CV4 7AL, UK
Fax: +44(2476)524112; e-Mail: a.j.clark@warwick.ac.uk;
Further Information

Publication History

Received 8 October 2009
Publication Date:
22 December 2009 (online)

Abstract

Reaction of N-butyl-N-(2-bromo-2-methylpropionyl)-arylsulfonamides with CuBr/tripyridylamine leads to amidyl radicals via 1,4-aryl migration with concomitant loss of SO2, which can further undergo cyclisation to oxindoles or reduction to amides with the ratio dependent upon the temperature and solvent utilised.

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2-Bromo-N-butyl-2-methyl-N-4-tolylpropanamide (1.50 g, 4.8 mmol) was added to anhyd AlCl3 (1.62 g, 12.1 mmol) under a stream of nitrogen. The mixture was heated at 50 ˚C for 10 min and then maintained at 160 ˚C for 1 h. The mixture was washed with H2O (5 × 50 mL) and extracted with Et2O, dried over MgSO4, and evaporated to give 16c (0.45 g, 41%) after chromatography (PE-EtOAc, 10:1); R f  = 0.40 (PE-EtOAc, 10:1). IR: νmax = 2962, 2929, 2865, 1705, 1619, 1599, 1493, 1381, 1351, 1192 cm. ¹H NMR (400 MHz, CDCl3): δ = 7.04 (1 H, d, J = 8.0 Hz), 7.03 (1 H, s), 6.75 (1 H, d, J = 8.0 Hz), 3.69 (2 H, t, J = 8.0 Hz), 2.34 (3 H, s), 1.65 (2 H, quin, J = 8.0 Hz), 1.35 (2 H, sext, J = 8.0 Hz), 1.35 (3 H, s), 0.94 (3 H, t, J = 8.0 Hz). ¹³C NMR (75.5 MHz, CDCl3): δ = 181.3, 139.7, 136.1, 131.7, 127.7, 123.3, 108.1, 44.1, 39.6, 29.5, 24.5, 21.1, 20.1, 13.8. ESI-HRMS: m/z calcd for Na+C15H21NO: 254.1515; found [Na+]: 254.1522.
Data for the Mixture of 8c and 19
IR: νmax = 2963, 2931, 2871, 1707, 1606, 1462, 1383, 1343, 1223 cm. ESI-HRMS: m/z calcd for Na+C15H21NO: 254.1515; found [Na+]: 254.1519.
Data for 19
¹H NMR (400 MHz, CDCl3): δ = 7.14 (1 H, t, J = 8.0 Hz), 6.81 (1 H, d, J = 8.0 Hz), 6.71 (1 H, d, J = 8.0 Hz), 3.70 (2 H, t, J = 8.0 Hz), 2.40 (3 H, s), 1.65 (2 H, quin, J = 8.0 Hz), 1.44 (3 H, s), 1.37 (2 H, sext, J = 8.0 Hz), 0.94 (3 H, t, J = 8.0 Hz). ¹³C NMR (75.5 MHz, CDCl3): δ = 181.3, 142.3, 134.2, 132.8, 127.4, 124.7, 106.1, 44.9, 39.6, 29.5, 22.4, 20.1, 18.2, 13.8.
Data for 8c
¹H NMR (400 MHz, CDCl3): δ = 7.08 (1 H, d, J = 8.0 Hz), 6.86 (1 H, d, J = 8.0 Hz), 6.68 (1 H, s), 3.69 (2 H, t, J = 8.0 Hz), 2.38 (3 H, s), 1.65 (2 H, quin, J = 8.0 Hz), 1.37 (2 H, sext, J = 8.0 Hz), 1.34 (3 H, s), 0.95 (3 H, t, J = 8.0 Hz). ¹³C NMR (75.5 MHz, CDCl3): δ = 181.3, 142.3, 137.6, 133.2, 122.6, 122.1, 109.2, 43.8, 39.5, 29.6, 24.6, 21.8, 20.1, 13.8.

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A typical procedure is illustrated for reaction of 1b with CuBr (entry 2, Table  [¹] ). Substrate 1b (0.3 mmol) was added to dry CH2Cl2 (2 mL), and CuBr (0.33 mmol) and tripyridylamine (0.33 mmol) were added. The reaction mixture was heated at 40 ˚C for 18 h. Upon cooling, the crude mixture was passed through a small silica plug (eluting with EtOAc, 20 mL to remove copper residues). After evaporation of the solvent and chromatography (PE-EtOAc, 8:1) a mixture of amide 3b and oxindole 8b were isolated in the ratio of 1.4:1.0, combined yield 78%. Spectroscopic data for 3b were identical to an authentic sample prepared previously²,9 and data for 8b were identical to that reported above.¹4