Synthesis of New 2-Benzazepino[4,5-a]naphthalene Derivatives via
1,7-Electrocyclisation of Nonstabilised Azomethine Ylides

Tibor Novak; Zoltán Mucsi; Barbara Balázs; László Keresztély; Gábor Blaskó; Miklós Nyerges

doi:10.1055/s-0030-1258036

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Synlett 2010(16): 2411-2414
DOI: 10.1055/s-0030-1258036

LETTER

Synthesis of New 2-Benzazepino[4,5-a]naphthalene Derivatives via 1,7-Electrocyclisation of Nonstabilised Azomethine Ylides

Tibor Novak, Zoltán Mucsi, Barbara Balázs, László Keresztély, Gábor Blaskó, Miklós Nyerges*
Servier Research Institute of Medicinal Chemistry, Záhony u. 7., 1031 Budapest, Hungary
Fax: +36(1)8812011; e-Mail: miklos.nyerges@hu.netgrs.com;

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Publication History

Received 9 June 2010
Publication Date:
12 August 2010 (online)

Abstract
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Abstract

Novel 2-benzazepino[4,5-a]naphthalene derivatives were synthesised efficiently via 1,7-electrocyclisation of nonstabilised azomethine ylides derived from 1-aryl- or 1-alkenyl-naphthalene-2-carbaldehyde derivatives. In some cases, surprisingly, pyrrole derivatives were isolated. A mechanism for the formation of the pyrrole byproduct is proposed.

Key words

Azepines - electrocyclic reactions - heterocycles - tandem reactions - ylides

References and Notes

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22

Experimental Procedure for 1,7-Electrocyclisation Reactions
The aldehyde (3 or 19, 1.0 mmol) was dissolved in xylene (50 mL), and the corresponding amino acid (2.0 mmol) was added. The reaction mixture was refluxed under Dean-Stark conditions and further portions of the amino acid (1.0 mmol) were added every 2 h until the starting aldehyde completely disappeared (2-6 h) judged by TLC. All the solvent was removed in vacuo, and the residue was purified by column chromatography (eluent: heptane-EtOAc).
Selected Data of Representative Examples
Compound 6a: ^¹H NMR (400 MHz, CDCl₃): δ = 7.24 (d, 1 H, J = 8.0 Hz, H-13), 6.97 (d, 1 H, J = 8.4 Hz, H-1), 6.92 (d, 1 H, J = 2.0 Hz, H-10), 6.90 (dd, 1 H, J = 8.0, 2.0 Hz, H-12), 6.78 (d, 1 H, J = 2.8 Hz, H-4), 6.65 (d, 1 H, J = 8.4, 2.8 Hz, H-2), 3.86 (s, 3 H, OMe), 3.81 (s, 3 H, OMe), 3.45 (br m, 1 H, H-5), 3.40 (br m, 1 H, H-5), 3.03 (br m, 1 H, H-7), 2.97 (br m, 2 H, H-7 and H-9), 2.76 (br m, 2 H, H-8 and H-9), 2.42 (br m, 1 H, H-8), 2.41 (s, 3 H, NMe). ^¹³C NMR (100 MHz, CDCl₃): δ = 158.3 (q), 138.5 (2 × q), 137.9 (q), 134.9 (q), 131.5 (q), 130.6 (q), 129.6 (CH), 127.7 (q), 127.1 (CH), 114.7 (CH), 113.8 (CH), 112.9 (CH), 110.8 (CH), 58.1 (CH₂), 57.8 (CH₂), 55.4 (2 × CH₃), 43.8 (CH₃), 31.3 (CH₂), 29.1 (CH₂). IR (KBr): 2935, 1605, 1251 cm^-¹.
Compound 13b: ^¹H NMR (500 MHz, DMSO-d₆): δ = 8.06 (s, 1 H, H-12), 7.96 (d, 1 H, J = 8.0 Hz, H-14), 7.36 (d, 1 H, J = 8.0 Hz, H-15), 6.84 (d, 1 H, J = 1.9 Hz, H-4), 6.76 (d, 1 H, J = 8.5 Hz, H-1), 6.70 (dd, 1 H, J = 1.9, 8.5 Hz, H-2), 4.45 (d, 1 H, J = 10.2 Hz, H-9), 4.32 (d, 1 H, J = 10.2 Hz, H-9), 4.31 (t, 1 H, J = 8.8 Hz, H-11a), 3.88 (s, 3 H, OMe), 3.75 (s, 3 H, OMe), 3.39 (d, 1 H, J = 15.0 Hz, H-7), 3.21 (d, 1 H, J = 15.0 Hz, H-7), 2.93 (m, 1 H, H-6), 2.89 (t, 1 H, J = 8.8 Hz, H-11), 2.86 (m, 1 H, H-6), 2.70 (m, 2 H, H-5), 2.60 (t, 1 H, J = 8.8 Hz, H-11). ^¹³C NMR (125 MHz, DMSO-d₆): δ = 166.3 (q),158.8 (q), 143.4 (q), 140.0 (q), 139.0 (q), 138.3 (q), 132.9 (q), 131.8 (CH), 130.4 (CH), 128.9 (q), 128.7 (CH), 127.4 (q), 126.3 (CH), 114.2 (CH), 111.7 (CH), 70.9 (CH), 62.8 (CH₂), 56.4 (CH₂), 55.5 (CH₃), 52.6 (CH₃), 38.6 (CH₂), 30.5 (CH₂), 28.5 (CH₂). IR (KBr): 2931, 1717, 1606, 1252, 1111 cm^-¹.
Compound 15a: ^¹H NMR (500 MHz, CDCl₃): δ = 8.14 (d, 1 H, J = 1.0 Hz, H-15), 7.96 (dd, 1 H, J = 8.0, 1.0 Hz, H-17), 7.36 (d, 1 H, J = 8.0 Hz, H-18), 7.20 (d, 1 H, J = 8.5 Hz, H-13), 7.11 (m, 2 H, H-11 and H-12), 7.04 (d, 1 H, J = 8.5 Hz, H-10), 6.87 (d, 1 H, J = 2.5 Hz, H-4), 6.81 (d, 1 H, J = 8.5 Hz, H-1), 6.68 (dd, 1 H, J = 2.5, 8.5 Hz, H-2), 3.90 (s, 3 H, OMe), 3.88 (d, 1 H, J = 17.8 Hz, H-9), 3.83 (d, 1 H, J = 17.8 Hz, H-9), 3.74 (s, 3 H, OMe), 3.52 (t, 1 H, J = 13.0 Hz, H-14), 3.19 (d, 1 H, J = 14.7 Hz, H-7), 3.15 (d, 1 H, J = 14.7 Hz, H-7), 3.15 (t, 1 H, J = 13.0 Hz, H-14a), 2.96 (d, 1 H, J = 13.0 Hz, H-14), 2.81 (m, 2 H, H-5), 2.66 (m, 1 H, H-6), 2.51 (m, 1 H, H-6). ^¹³C NMR (125 MHz, CDCl₃): δ = 166.6 (q), 158.8 (q), 145.5 (q), 140.6 (q), 138.6 (q), 135.3 (q), 134.6 (q), 133.6 (q), 129.1 (CH), 128.8 (CH), 128.7 (q), 128.2 (CH), 127.0 (CH), 126.9 (q), 126.4 (2 × CH), 126.3 (CH), 126.1 (CH), 114.2 (CH), 111.6 (CH), 58.2 (CH), 57.1 (CH₂), 56.7 (CH₂), 55.6 (CH₃), 52.7 (CH₃), 32.7 (CH₂), 32.6 (CH₂), 28.8 (CH₂). IR (KBr): 2928, 1717, 1606, 1251, 1109 cm^-¹.
Compound 21b: ^¹H NMR (500 MHz, CDCl₃): δ = 7.42 (d, 1 H, J = 8.4 Hz, H-9), 7.35 (t, 2 H, J = 8.4 Hz, Ph-3′ and 5′H), 7.29 (t, 1 H, J = 8.4 Hz, Ph-4′H), 7.06 (d, 2 H, J = 8.4 Hz, Ph-2′ and 6′H), 6.87 (d, 1 H, J = 3.6 Hz, H-6), 6.83 (dd, 1 H, J = 8.4, 3.6 Hz, H-8), 6.43 (s, 1 H, H-3), 5.19 (d, 1 H, J = 16.8 Hz, CH₂Ph), 5.11 (d, 1 H, J = 16.8 Hz, CH₂Ph), 4.31 (q, 1 H, J = 7.6 Hz, CHCH₃), 3.85 (s, 3 H, OMe), 3.51 (s, 3 H, CO₂Me), 2.86 (m, 2 H, H₂-4), 2.68 (m, 2 H, H₂-5), 1.50 (d, 3 H, J = 7.6 Hz, CHCH₃). ^¹³C NMR (125 MHz, CDCl₃): δ = 174.2 (q), 157.0 (q), 138.9 (q), 138.6 (q), 128.6 (2 × CH), 127.3 (2 × CH), 126.4 (CH), 125.8 (q), 125.2 (q), 124.9 (CH), 120.5 (q), 118.6 (q), 117.2 (CH), 114.6 (CH), 111.5 (CH), 55.3 (CH₃), 52.1 (CH₃), 50.7 (CH₂), 36.9 (CH), 32.0 (CH₂), 21.2 (CH₂), 16.1 (CH₃). IR (KBr): 2938, 1722, 1612, 1253, 1108 cm^-¹.