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The synthesis of azabicyclo[4.2.1]nonenes by the addition of a cyclopropenone to 4-vinyl substituted 1-azetines-isomers of the homotropane nucleus

Hemming, Karl, O'Gorman, P.A. and Page, Michael I. (2006) The synthesis of azabicyclo[4.2.1]nonenes by the addition of a cyclopropenone to 4-vinyl substituted 1-azetines-isomers of the homotropane nucleus. Tetrahedron Letters, 47. pp. 425-428. ISSN 0040-4039

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Abstract

The conversion of 4-vinyl substituted β-lactams into 4-vinyl substituted 1-azetines and their subsequent reaction with diphenylcyclopropenone (DPP) results in the formation of a highly functionalised 7-azabicyclo[4.2.1]nonene. This heterocyclic system is an isomer of the homotropane (9-azabicyclo[4.2.1]nonene) nucleus, which is the core structure of a class of alkaloid natural products that includes anatoxin-a. The key processes involved are two ring expansions, one of which constitutes a formal [3+2] cycloaddition and the other of which is an unusual aza-Cope (amino-Claisen) [3,3]-sigmatropic rearrangement.

Item Type: Article
Additional Information: Copyright © 2007 Elsevier B.V. All rights reserved. ScienceDirect® is a registered trademark of Elsevier B.V.
Subjects: Q Science > QD Chemistry
Schools: School of Applied Sciences
School of Applied Sciences > Biomolecular Sciences Research Centre
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12

Fresh Meerwein’s reagent gave yields of 2-ethylthio-1-azetines 8 at the higher end of the range. The conversion of the 4-vinyl β-lactams 6 into the corresponding 2-ethoxy-1-azetines was unsuccessful.

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17

All new compounds gave satisfactory 1H/13C NMR spectra, mass spectra and HRMS/microanalysis.

18

Typical experimental and spectroscopic details for compounds 12: To a stirred solution of 2-ethylthio-4-vinyl-1-azetine 8 (0.1–0.5 g) in anhydrous acetonitrile (10–20 mL) was added, with stirring and under an atmosphere of dry nitrogen, a solution of diphenylcyclopropenone (1.0 M equiv) in acetonitrile (5–20 mL). The mixture was stirred at room temperature until the reaction was complete (one week) and the solvent was removed by rotary evaporation. The crude product was purified by flash silica column chromatography (petroleum ether–ethyl acetate/2:1). As an example, 6-ethylthio-3,4-dimethyl-1,8-diphenyl-7-azabicyclo[4.2.1]nona-3,7-dien-9-one 12c was obtained as a dark orange solid (0.271 g, 62% yield), mp 177–181 °C, from 1-azetine 8c (0.195 g, 1.16 mmol) and DPP (0.240 g, 1.16 mmol). δH (400 MHz, CDCl3): 1.28 (3H, t, J = 7.4, CH3CH2), 1.695 (3H, s, Me), 1.700 (3H, s, Me), 2.55 (1H, dq, J = 11.3, 7.4, CH2CH3), 2.66 (1H, dq, J = 11.5, 7.5, CH2CH3), 2.76 (1H, d, J = 16.8, CH2CMe), 2.85 (1H, d, J = 16.8, CH2CMe), 2.97 (1H, d, J = 16.3, CH2CMe), 3.22 (1H, d, J = 16.2, CH2CMe), 7.14 (2H, dd, J = 6.5, 1.6, 2 × ArH), 7.23–7.30 (3H, m, 3 × ArH), 7.32–7.39 (3H, m, 3 × ArH), 7.66 (2H, dd, J = 7.5, 1.0, 2 × ArH). δC (100 MHz, CDCl3): 14.3 (Me), 23.3 (Me), 23.6 (Me), 23.8 (CH2), 42.5 (CH2), 46.0 (CH2), 63.5 (q), 83.0 (q), 124.0 (q), 125.2 (q), 127.1 (CH), 127.9 (CH), 128.2 (CH), 128.3 (CH), 129.0 (CH), 130.8 (CH), 132.2 (q), 136.7 (q), 173.7 (q), 215.1 (q). νmax (thin film, cm−1): 3057 (m), 2986 (m), 2930 (m), 1737 (s), 1566 (m), 1446 (s), 1374 (m), 1266 (s), 1245 (s), 1046 (m), 739 (s), 700 (s). EI+ mass spectrum (m/z, %): 376 ([M++1], 5%), 375 ([M]+, 10%), 347 (28%), 318 (45%), 293 (50%), 264 (100%), 178 (74%), 105 (25%), 91 (40%), 77 (48%), 41 (38%). HRMS [CI+(NH3)]: Found [M+H+] 376.1730, C24H26NOS requires 376.1732.

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Depositing User: Briony Heyhoe
Date Deposited: 13 Jul 2007
Last Modified: 17 Oct 2008 16:45
URI: http://eprints.hud.ac.uk/id/eprint/220

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