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

Metadata only available from this repository.

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
Related URLs:	Author Author
References:	1 (a) For relevant reviews, see:J.W. Daly, Cell. Mol. Neurobiol. 25 (2005), pp. 513–552. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (b) H.L. Mansell, Tetrahedron 52 (1996), pp. 6025–6061. Abstract | Abstract + References | PDF (1288 K) | View Record in Scopus | Cited By in Scopus 2 (a) J.P. Devlin, O.E. Edwards, P.R. Gorham, N.R. Hunter, R.K. Pike and B. Stavric, Can. J. Chem. 55 (1977), pp. 1367–1371. (b) P.J. Parsons, N.P. Camp, N. Edwards and L.R. Sumoreeah, Tetrahedron 56 (2000), pp. 309–315. SummaryPlus | Full Text + Links | PDF (160 K) | View Record in Scopus | Cited By in Scopus (c) J.B. Brenneman and S.F. Martin, Org. Lett. 6 (2004), pp. 1329–1331. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (d) T. Hjelmgaard, I. Søtofte and D. Tanner, J. Org. Chem. 70 (2005), pp. 5688–5697. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus 3 (a) D.B. Kanne, D.J. Ashworth, M.T. Cheng, L.C. Mutter and L.G. Abood, J. Am. Chem. Soc. 108 (1986), pp. 7864–7865. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (b) E. Wright, T. Gallagher, C.G.V. Sharples and S. Wonnacott, Bioorg. Med. Chem. Lett. 7 (1997), pp. 2867–2870. SummaryPlus | Full Text + Links | PDF (219 K) | View Record in Scopus | Cited By in Scopus (c) H. Gohlke, D. Gündisch, S. Schwarz, G. Seitz, M.C. Tilotta and T. Wegge, J. Med. Chem. 45 (2002), pp. 1064–1072. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (d) D. Gündisch, T. Kämpchen, S. Schwarz, G. Seitz, J. Siegl and T. Wegge, Bioorg. Med. Chem. 10 (2002), pp. 1–9. SummaryPlus | Full Text + Links | PDF (209 K) 4 (a) N. Takada, M. Iwatsuki, K. Suenaga and D. Uemura, Tetrahedron Lett. 41 (2000), pp. 6425–6428. SummaryPlus | Full Text + Links | PDF (149 K) | View Record in Scopus | Cited By in Scopus (b) H. Kigoshi, N. Hayashi and D. Uemura, Tetrahedron Lett. 42 (2001), pp. 7469–7471. SummaryPlus | Full Text + Links | PDF (65 K) | View Record in Scopus | Cited By in Scopus 5 (a) J.R. Malpass, D.A. Hemmings and A.L. Wallis, Tetrahedron Lett. 37 (1996), pp. 3911–3914. SummaryPlus | Full Text + Links | PDF (236 K) | View Record in Scopus | Cited By in Scopus (b) J.R. Malpass, D.A. Hemmings, A.L. Wallis, S.R. Fletcher and S. Patel, J. Chem. Soc., Perkin Trans. 1 (2001), pp. 1044–1050. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus 6 K. Hemming, D.T. Morgan and R.K. Smalley, J. Fluorine Chem. 106 (2000), pp. 83–86. SummaryPlus | Full Text + Links | PDF (154 K) | View Record in Scopus | Cited By in Scopus 7 (a) K. Hemming, A.D. Redhouse, R.K. Smalley, J.R. Thompson, P.D. Kennewell and R. Westwood, Tetrahedron Lett. 33 (1992), pp. 2231–2234. Abstract | Abstract + References | PDF (204 K) | View Record in Scopus | Cited By in Scopus (b) K. Hemming, A.-B.N. Luheshi, A.D. Redhouse, R.K. Smalley, J.R. Thompson, P.D. Kennewell and R. Westwood, Tetrahedron 49 (1993), pp. 4383–4408. Abstract | Abstract + References | PDF (1496 K) | View Record in Scopus | Cited By in Scopus 8 W.Y. Tsang, N. Ahmed, L.P. Harding, K. Hemming, A.P. Laws and M.I. Page, J. Am. Chem. Soc. 127 (2005), pp. 8946–8947. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus 9 (a) M.I. Page, Acc. Chem. Res. 34 (2004), pp. 297–303. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (b) A. Llinas, N. Ahmed, M. Cordaro, A.P. Laws, J.M. Frere, M. Delmarcelle, N.R. Silvaggi, J.A. Kelly and M.I. Page, Biochemistry 44 (2005), pp. 7738–7746. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (c) N. Ahmed, W.Y. Tsang and M.I. Page, Org. Lett. 6 (2004), pp. 201–203. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus 10 (a) T. Durst and M.J. O’Sullivan, J. Org. Chem. 35 (1970), pp. 2043–2044. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (b) D. Freitag, P. Schwab and P. Metz, Tetrahedron Lett. 45 (2004), pp. 3589–3592. SummaryPlus | Full Text + Links | PDF (295 K) | View Record in Scopus | Cited By in Scopus (c) D.N. Dhar and K.S.K. Murthy, Synthesis (1986), pp. 437–449. Full Text via CrossRef (d) G.S. Singh, Tetrahedron 59 (2003), pp. 7631–7649. SummaryPlus | Full Text + Links | PDF (973 K) | View Record in Scopus | Cited By in Scopus 11 (a) S. Scheibye, B.S. Pedersen and S.O. Lawesson, Bull. Soc. Chim. Belg. 87 (1978), pp. 229–238. View Record in Scopus | Cited By in Scopus (b) For a review, see:M. Jesberger, T.P. Davis and L. Barner, Synthesis (2003), pp. 1929–1958. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus 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. 13 G. Pifferi, P. Consonni, G. Pelizza and E. Testa, J. Heterocycl. Chem. 4 (1967), pp. 619–624. 14 H. Heimgartner, F. Stierli, R. Prewo and J.H. Bieri, Helv. Chim. Acta 66 (1983), pp. 1366–1375. 15 (a) T. Eicher and R. Rohde, Synthesis (1985), pp. 619–625. Full Text via CrossRef (b) T. Eicher, F. Abdesaken, G. Franke and J.L. Weber, Tetrahedron Lett. 16 (1975), pp. 3915–3918. Abstract | Abstract + References | PDF (181 K) (c) T. Eicher, J.L. Weber and G. Chatila, Liebigs Ann. Chem. (1978), pp. 1203–1221. 16 (a) M.A.M. Gomaa, J. Chem. Soc., Perkin Trans. 1 (2002), pp. 341–344. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (b) N. Abe, T. Murafuji, Y. Sugihara and A. Kakehi, Heterocycles 41 (1995), pp. 2289–2298. 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. 19 (a) L. Viallon, O. Reinaud, P. Capdevielle and M. Maumy, Tetrahedron Lett. 36 (1995), pp. 4787–4790. SummaryPlus | Full Text + Links | PDF (193 K) | View Record in Scopus | Cited By in Scopus (b) L. Viallon, O. Reinaud, P. Capdevielle and M. Maumy, Tetrahedron 52 (1996), pp. 13605–13614. Abstract | Abstract + References | PDF (515 K) | View Record in Scopus | Cited By in Scopus
Depositing User:	Briony Heyhoe
Date Deposited:	13 Jul 2007
Last Modified:	07 Apr 2018 20:15
URI:	http://eprints.hud.ac.uk/id/eprint/220

Downloads

Repository Staff Only: item control page

View Item