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Synlett 2002(1): 0149-0151
DOI: 10.1055/s-2002-19354
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Approach to α-Aryl β-Amino Esters through 1,2-Aryl Migration of p-Toluenesulfonic Acid Mediated Diazo Decomposition

Nan Jiang, Jianbo Wang*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry, Peking University, Beijing 100871, China
Fax: +86(10)62751708; e-Mail: wangjb@pku.edu.cn;
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Publication History

Received 5 October 2001
Publication Date:
01 February 2007 (online)

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Abstract

A new method for the synthesis of α-aryl β-amino esters has been developed. The key step in this preparation is the chemoselective 1,2-aryl migration of diazo carbonyl compounds catalyzed by TsOH.

Key words

diazo compounds - 1,2-aryl migration - amino acids - hydrogenations - α-aryl β-amino esters

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General procedure for the TsOH catalyzed diazo decomposition: To a solution of TsOH (1 mg) in anhydrous CH2Cl2 (20 mL) at 0 °C under N2, was added dropwise a solution of diazo compound in anhydrous CH2Cl2 (5 mL). The reaction was complete within 30 min as indicated by TLC check. Solvent was removed by evaporation, and the residue was purified by flash column chromatography to give cis and trans α-aryl-β-enamino esters as a mixture.

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General procedure for the hydrogenation of a-aryl-b-enamino esters: To a solution of α-aryl-β-enamino esters (50 mg, cis and trans mixture) in absolute MeOH (25 mL) was added 10% Pd/C catalyst (10 mg). The reaction mixture was stirred for 10 h under 1 atm hydrogen atmosphere. Then catalyst was removed by filtration and solvent was evaporated to give a residue, which was purified by flash column chromatography. 3a: 1H NMR (200 MHz, CDCl3): δ 1.13 (t, 3 H), 2.36 (s, 3 H), 3.19-352 (m, 2 H), 3.79-3.86 (q, 1 H), 4.04-4.17 (m, 2 H), 5.13 (t, 1 H), 7.13 (m, 7 H), 7.72 (d, 2 H); 13C NMR (50 MHz, CDCl3): δ 13.88, 21.42, 45.62, 51.72, 61.27, 126.91, 127.82, 127.84, 128.88, 129.68, 135.63, 136.86, 143.40, 172.34; MS m/z (relative intensity): 347 (M+, 17%), 118 (100%). 3b: 1H NMR (200 MHz, CDCl3) δ 1.18 (t, 3H), 2.42 (s, 3 H), 3.16-3.50 (m, 2H), 3.77-3.81 (m, 1 H), 3.79 (s, 3H), 4.04-4.17 (m, 2 H), 5.07 (t, 1 H), 6.83 (d, 2 H), 7.06 (d, 2 H), 7.29 (d, 2 H), 7.72 (d, 2 H); 13C NMR (50 MHz, CDCl3): δ 13.90, 21.41, 45.67, 50.82, 55.14, 61.18, 114.25, 126.91, 127.60, 128.90, 129.65, 136.90, 143.36, 159.14, 172.56; MS m/z (relative intensity): 377 (M+, 10%), 194 (100%). 3c: 1H NMR (200 MHz, CDCl3) δ 1.19 (t, 3 H), 2.39 (s, 3 H), 3.21-3.55 (m, 2 H), 3.84-3.91(q, 1 H), 4.04-4.20 (m, 2 H), 5.07 (t, 1 H), 7.20-7.57 (m, 1 1H), 7.71 (d, 2 H); 13C NMR (50 MHz, CDCl3): δ 13.96, 21.45, 45.65, 51.40, 61.39, 126.95, 127.45, 127.60, 128.30, 129.71, 134.60, 136.89, 140.26, 140.82, 143.45, 172.36. m/z (relative intensity): 423 (M+, 11%), 240 (100%). 3d: 1H NMR (200 MHz, CDCl3) δ 1.17 (t, 3 H), 2.42 (s, 3 H), 3.15-3.50 (m, 2 H), 3.78-3.85 (q, 1 H), 4.04-4.18 (m, 2 H), 5.20 (t, 1 H), 6.92-7.30 (m, 6 H), 7.70 (d, 2 H); 13C NMR (50 MHz, CDCl3): δ 13.87, 21.41, 45.57, 50.92, 61.37, 115.55, 115.98, 126.89, 129.44, 129.60, 129.69, 136.79, 143.47, 172.19. m/z (relative intensity): 365 (M+, 24%), 182 (100%). 3e: 1H NMR (200 MHz, CDCl3) δ 1.18 (t, 3 H), 2.42 (s, 3 H), 3.20-3.55 (m, 2 H), 3.87-3.94 (q, 1 H), 4.04-4.17 (m, 2 H), 5.13 (t, 1 H), 7.29 (m, 2 H), 7.31-7.56 (m, 4 H), 7.70 (m, 2 H); 13C NMR (50 MHz, CDCl3): δ 13.84, 21.42, 45.44, 51.55, 61.61, 124.74, 124.81, 126.91, 129.42, 131.44, 136.68, 136.78, 143.62, 171.70. m/z (relative intensity): 415 (M+, 8%) 184 (100%). 3f: 1H NMR (200 MHz, CDCl3) δ 1.22 (t, 3 H), 1.97 (m, 2 H), 2.39 (s, 3 H), 2.83 (t, 2 H), 3.89 (d, 2 H), 4.02-4.20 (m, 4 H), 5.15 (t, 1 H), 7.23 (d, 2 H), 7.68 (d, 2 H); 13C NMR (50 MHz, CDCl3): δ 14.32, 21.40, 23.74, 31.15, 39.35, 59.84, 72.16, 76.36, 76.99, 77.63, 98.03, 127.10, 129.11, 137.59, 142.79, 167.55, 173.76. m/z (relative intensity): 339 (M+, 14%), 184 (100%).

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For the α-aryl-β-enamino esters 5f and 6f, the hydrogenation gave a product with the furanyl moiety being partially hydrogenated. The structure of the 3f (Figure) is as follows.

Figure