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Synlett 2006(14): 2275-2277  
DOI: 10.1055/s-2006-949654
LETTER
© Georg Thieme Verlag Stuttgart · New York

Sequential Amino-Claisen Rearrangement/Intramolecular 1,3-Dipolar ­Cycloaddition/Reductive Cleavage Approach to the Stereoselective Synthesis of cis-4-Hydroxy-2-aryl-2,3,4,5-tetrahydro-1(1H)-benzazepines

Sandra Liliana Gómez Ayalaa, Elena Stashenkoa, Alirio Palma*a, Alí Bahsasb, Juan Manuel Amaro-Luisb
a Laboratorio de Síntesis Orgánica, Centro de Investigación en Biomoléculas, Escuela de Química, , Universidad Industrial de Santander, A.A., 678 Bucaramanga, Colombia
Fax: +57(76)349069; e-Mail: apalma@uis.edu.co;
b Laboratorio de RMN, Grupo de Productos Naturales, Departamento de Química, Universidad de Los Andes, Mérida 5101, Venezuela
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Publication History

Received 18 May 2006
Publication Date:
24 August 2006 (online)

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Abstract

A novel stereoselective synthesis of cis-2-aryl-4-hydroxy-2,3,4,5-tetrahydro-1-benzazepines from N-allylanilines utilizing aromatic amino-Claisen rearrangement and intramolecular 1,3-dipolar cycloaddition methodologies is described. This sequence involves N-allylation of corresponding N-benzylanilines followed by amino-Claisen rearrangement, subsequent oxidation with in situ 1,3-dipolar cycloaddition affording isoxazolidines, and finally reductive cleavage of the isoxazolidinic N-O bond.

Key words

amino-Claisen rearrangement - intramolecular 1,3-dipolar cycloaddition - tetrahydro-1-benzazepines - ortho-allylanilines - reductive cleavage

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17

NMR data for exo-cycloadduct 4a: 1H NMR (400 MHz, CDCl3): δ = 2.58 (1 H, d, J = 16.5 Hz, 5-HA), 2.61-2.69 (2 H, m, 3-HAHB), 3.45 (1 H, dd, J = 16.6, 5.4 Hz, 5-HB), 4.62 (1 H, dd, J = 11.2, 4.4 Hz, 2-H), 4.97 (1 H, m, 4-H), 7.12 (1 H, dd, J = 6.6, 2.1 Hz, 9-H), 7.15-7.24 (3 H, m, 6-H, 7-H, 8-H), 7.30 (1 H, t, J = 7.6 Hz, 4′-H), 7.39 (2 H, t, J = 7.6 Hz, 3′-H, 5′-H), 7.50 (2 H, d, J = 7.2 Hz, 2′-H, 6′-H). 13C NMR (100 MHz, CDCl3): δ = 34.6 (5-C), 42.7 (3-C), 75.1 (4-C), 75.3 (2-C), 121.9 (9-C), 125.2 (5a-C), 125.9 (7-C), 126.4 (2′-C, 6′-C), 126.5 (8-C), 126.9 (4′-C), 128.4 (3′-C, 5′-C), 129.8 (6-C), 143.8 (1′-C), 150.9 (9a-C).

18

NMR data for cis-stereoisomer 5a: 1H NMR (400 MHz, CDCl3): δ = 2.14 (1 H, ddd, J = 11.0, 10.7, 10.5 Hz, 3-Hax), 2.22 (1 H, ddt, J = 11.0, 2.9, 1.9 Hz, 3-Heq), 3.03 (1 H, dt, J = 13.6, 1.9 Hz, 5-Heq), 3.13 (1 H, dd, J = 13.6, 10.5 Hz, 5-Hax), 3.88 (1 H, tdd, J = 10.5, 2.9, 1.9 Hz, 4-Hax), 3.98 (1 H, dd, J = 11.0, 1.9 Hz, 2-Hax), 6.70 (1 H, d, J = 7.6 Hz, 9-H), 6.92 (1 H, t, J = 7.6 Hz, 7-H), 7.10 (1 H, t, J = 7.6 Hz, 8-H), 7.18 (1 H, d, J = 7.6 Hz, 6-H), 7.35 (1 H, t, J = 6.9 Hz, 4′-H), 7.39 (2 H, d, J = 6.9 Hz, 2′-H, 6′-H), 7.43 (2 H, t, J = 6.9 Hz, 3′-H, 5′-H). 13C NMR (100 MHz, CDCl3): δ = 44.7 (5-C), 48.5 (3-C), 61.3 (2-C), 70.0 (4-C), 120.1 (9-C), 121.8 (7-C), 126.6 (2′-C, 6′-C), 127.4 (8-C), 127.8 (4′-C), 128.0 (5a-C), 128.9 (3′-C, 5′-C), 131.6 (6-C), 145.1 (1′-C), 149.4 (9a-C).