Thermal Fragmentation of 5-Spirocyclobutane-isoxazolidines
nitrone 10b (112 mg, 0.53 mmol) and norbornene (75 mg,
0.79 mmol) in toluene (0.25 mL) was heated at 100–110 °C in a
Sovirel tube for 4 d. The reaction mixture was concentrated under
reduced pressure, and the crude product was purified by flash
chromatography on silica gel (petroleum ether/ CH2Cl2, 1:1) to give
44a (99 mg, 0.324 mmol 61% yield) and 44b (34 mg, 0.111 mmol,
21% yield) as colorless crystalline solids. The relative trans and cis
orientation of hydrogen atoms 5-H/6-H in adducts 44 was deter-
mined by NOESY1D NMR spectroscopy.
Supporting Information (see footnote on the first page of this arti-
1
cle): Calculation parameters and H and 13C NMR spectra.
Acknowledgments
We thank the Ministry of University and Research (MIUR, Rome,
Italy) for financial support (PRIN2008BRXNTY) and the Centro
Interdipartimentale di Spettrometria di Massa (CISM) of the Uni-
versity of Firenze for the HRMS analyses. B. Innocenti is acknowl-
edged for technical support.
44a: M.p. 66–68 °C (iPr2O); Rf = 0.32 (CH2Cl2/petroleum ether,
1
1:1). H NMR (400 MHz): δ = 7.46–7.42 (m, 2 H), 7.38–7.18 (m,
8 H), 4.08 (d, J = 6.6 Hz, 1 H), 3.90 (A part of an AB system, J =
14.5 Hz, 1 H), 3.62 (B part of an AB system, J = 14.5 Hz, 1 H),
3.21 (br. d, J = 7.2 Hz, 1 H), 2.34–2.53 (m, 2 H), 2.22 (br. s, 1 H),
1.82 (d, J = 10.2 Hz, 1 H), 1.57–1.39 (m, 2 H), 1.09 (d, J = 10.2 Hz,
1 H), 1.02–0.91 (m, 2 H) ppm. 13C NMR (50 MHz): δ = 140.1 (s),
137.8 (s), 128.5 (d, 4C), 127.9 (d, 2C), 127.7 (d, 2C), 127.5 (d),
126.8 (d), 83.9 (d), 75.6 (d), 61.9 (d), 59.1 (t), 39.4 (d), 38.1 (d),
[1] a) A. Brandi, S. Cicchi, F. M. Cordero, A. Goti, Chem. Rev.
2003, 103, 1213–1269; b) F. M. Cordero, F. De Sarlo, A.
Brandi, Monatsh. Chem. 2004, 135, 649–669.
[2] a) F. M. Cordero, F. Pisaneschi, A. Goti, J. Ollivier, J. Salaün,
A. Brandi, J. Am. Chem. Soc. 2000, 122, 8075–8076; b) F. M.
Cordero, F. Pisaneschi, M. Salvati, V. Paschetta, J. Ollivier, J.
Salaün, A. Brandi, J. Org. Chem. 2003, 68, 3271–3280.
[3] F. M. Cordero, M. Salvati, F. Pisaneschi, A. Brandi, Eur. J.
Org. Chem. 2004, 2205–2213.
32.5 (t), 27.7 (t), 23.2 (t) ppm. IR: ν = 3065, 3031, 2959, 2876,
˜
1603, 1496, 1454, 1369, 1342, 1230, 1141, 1078, 1043, 1027 cm–1.
MS (EI): m/z (%) = 305 (37) [M+], 228 (18), 214 (7), 91 (100).
C21H23NO (305.41): calcd. C 82.58, H 7.59, N 4.59; found C 82.20,
H 7.69, N 4.26.
[4] A. Brandi, S. Cicchi, F. M. Cordero, Chem. Rev. 2008, 108,
3988–4035.
[5] a) A. Goti, A. Brandi, F. De Sarlo, A. Guarna, Tetrahedron
Lett. 1986, 27, 5271–5274; b) F. M. Cordero, A. Goti, F.
De Sarlo, A. Guarna, A. Brandi, Tetrahedron 1989, 45, 5917–
5924; c) A. Goti, A. Brandi, F. De Sarlo, A. Guarna, Tetrahe-
dron 1992, 48, 5283–5300.
[6] E. Ochoa, M. Mann, D. Sperling, J. Fabian, Eur. J. Org. Chem.
2001, 4223–4231.
[7] A. de Meijere, M. von Seebach, S. I. Kozhushkov, R. Boese, D.
Blaser, S. Cicchi, T. Dimoulas, A. Brandi, Eur. J. Org. Chem.
2001, 3789–3795.
[8] A. Senthilvelan, G.-H. Lee, W.-S. Chung, Tetrahedron Lett.
2006, 47, 7179–7183.
44b: M.p. 116–118 °C (Et2O); Rf = 0.55 (CH2Cl2/petroleum ether,
1
1:1). H NMR (400 MHz): δ = 7.42–7.18 (m, 10 H), 4.20 (d, J =
6.4 Hz, 1 H), 4.05 (A part of an AB system, J = 14.8 Hz, 1 H), 3.95
(d, J = 7.8 Hz, 1 H), 3.61 (B part of an AB system, J = 14.8 Hz, 1
H), 2.58 (dd, J = 7.8, 6.4 Hz, 1 H), 2.42–2.36 (m, 2 H), 1.72 (br. d,
J = 3.1 Hz, 1 H), 1.45–1.23 (m, 2 H), 1.04–0.88 (m, 3 H) ppm. 13C
NMR (50 MHz): δ = 138.2 (s), 138.0 (s), 128.2 (d, 2 C), 128.0 (d,
4 C), 127.8 (d, 2 C), 127.0 (d), 126.6 (d), 84.7 (d), 73.0 (d), 60.7 (t),
57.4 (d), 42.1 (d), 36.9 (d), 34.6 (t), 28.5 (t), 23.9 (t) ppm. IR: ν =
˜
3065, 3030, 2958, 2874, 1602, 1496, 1473, 1453, 1373, 1333, 1318,
1259, 1165, 1072, 1026 cm–1. MS (EI): m/z (%) = 305 (33) [M+],
228 (1), 214 (21), 91 (100). C21H23NO (305.41): calcd. C 82.58, H
7.59, N 4.59; found C 82.19, H 7.98, N 4.47.
[9] a) T. Ono, V. P. Kukhar, V. A. Soloshonok, J. Org. Chem. 1996,
61, 6563–6569; b) G. E. Keck, T. T. Wager, S. F. McHardy, Tet-
rahedron 1999, 55, 11755–11772.
[10] R. Gandolfi, unpublished results.
[11] a) O. L. Chapman, J. Meinwald, J. Am. Chem. Soc. 1959, 81,
5800–5803; b) J. J. Tufariello, Sk. A. Ali, J. Am. Chem. Soc.
1979, 101, 7114–7116; c) S.-I. Murahashi, Y. Kodera, T. Ho-
somi, Tetrahedron Lett. 1988, 29, 5949–5952; d) F. Machetti,
F. M. Cordero, F. De Sarlo, A. Brandi, Tetrahedron 2001, 57,
4995–4998; e) F. M. Cordero, F. Machetti, F. De Sarlo, A.
Brandi, Gazz. Chim. Ital. 1997, 127, 25–29.
[12] For similar examples with formations of also iminium ions, see:
a) U. Chiacchio, F. Casuscelli, A. Corsaro, A. Rescifina, G.
Romeo, N. Uccella, Tetrahedron 1994, 50, 6671–6680; b) F. Ca-
suscelli, U. Chiacchio, A. Rescifina, R. Romeo, G. Romeo, S.
Tommasini, N. Uccella, Tetrahedron 1995, 51, 2979–2990.
[13] All calculations were carried out by using the Gaussian 03 suite
of programs with the B3LYP method. Bulk solvent effects were
evaluated with the SCRF theory using the PCM united atom
topological model (UAHF radii) as implemented in the C.02
revision of Gaussian 03.[14] For a more detailed description of
computational methods, see the Supporting Information.
Thermodynamic parameters of compounds 27–39 are reported
in Tables S1–S4 and geometries in Figures S1–S5 of the Sup-
porting Information.
[14] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T.
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N.
Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P.
Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R.
Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R.
Acid-Catalyzed Thermal Rearrangement of 44a: A solution of ad-
duct 44a (66.8 mg, 0.219 mmol) in toluene (3.6 mL) was treated
with TFA (0.05 mL, 0.656 mmol) at 0 °C for 10 min, was then
heated at 120 °C for 15 h. The reaction mixture was concentrated
under reduced pressure. GC–MS and 1H NMR analyses of the
crude residue product showed the presence of compounds 16, 17,
45, 46,[24] 47, and cis-/trans-48.[25,26] Separation by chromatography
on silica gel (petroleum ether/AcOEt from 10:1 to 5:1) gave a mix-
ture of 45 and 46 and enriched fractions of 47, 48 (cis/trans mix-
ture), and 49.[27] Only partial spectroscopic characterization of 45
and 47 was possible.
(2S*,3S*)-3-Benzoylbicyclo[2.2.1]hept-2-yl Trifluoroacetate (45):
Mixture with 46. 1H NMR (400 MHz): detectable signals δ = 5.41–
5.43 (m, 1 H), 3.73–3.70 (m, 1 H), 2.81–2.75 (m, 1 H), 2.56 (d, J
= 5.2 Hz, 1 H), 1.94 (dm, J = 10.3 Hz, 1 H), 1.50 (dm, J = 10.3 Hz,
1 H) ppm. MS (EI): m/z (%) = 312 (2) [M+], 245 (2), 198 (10), 120
(22), 105 (100), 77 (45), 69 (8).
[3-(Benzylamino)bicyclo[2.2.1]hept-2-yl](phenyl)methanone (47): En-
riched fraction. 1H NMR (400 MHz): δ = 8.00–7.96 (m, 2 H), 7.57–
7.51 (m, 1 H), 7.48–7.41 (m, 2 H), 7.27–7.16 (m, 5 H), 3.72–3.68
(m, 1 H), 3.70 (A part of an AB system, J = 12.9 Hz, 1 H), 3.59
(A part of an AB system, J = 12.9 Hz, 1 H), 2.82–2.78 (m, 1 H),
2.49–2.44 (m, 1 H), 2.37 (d, J = 4.0 Hz, 1 H), 1.90–1.81 (m, 1 H),
1.69 (tt, J = 12.2, 4.5 Hz, 1 H), 1.63–1.17 (m, 5 H) ppm. IR: ν =
˜
3065, 3028, 2956, 2872, 1676, 1448, 1211 cm–1. MS (EI): m/z (%)
= 305 (0.5) [M+], 214 (10), 146 (6), 105 (30), 91 (100), 77 (37).
Eur. J. Org. Chem. 2011, 5608–5616
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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