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

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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