B. Bonnaud, N. Mariet, B. Vacher
FULL PAPER
5.74 mmol) was added. The reaction mixture was warmed to room
temperature and stirred for 2 h, then quenched at 0 °C with water.
The precipitate was filtered off and the filtrate was extracted twice
with EtOAc. The combined organic layers were washed with brine,
dried (MgSO4), filtered and the solvent was distilled in vacuo. The
residue was purified by silica gel chromatography eluting with cy-
clohexane/EtOAc (97:3) to give 34 (0.49 g, 90%) as a colorless oil.
5a, 8, 10, 14, 15, 16, 17, 18, 20, 22, 29, 33, 36, 37, 38, 39, 40, 41,
43, 44, 45 and 48.
Acknowledgments
We thank Dr. Jean-Paul Ribet and Mr. P. Zalavari for analytical
support. Mr. Luc Petitpas’ assistance with bibliographic searches
is also very much appreciated.
R = 0.23 [cyclohexane/EtOAc (95:5)]. IR (film): ν = 1729 (C=O)
˜
f
cm–1 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.20 [s, 9 H,
.
C(CH3)3], 1.44 (s, 3 H, 2a-CH3), 1.65 (s, 3 H, 1-CH3), 2.83 (d, J =
17.2 Hz, 1 H, 7-H), 2.97 (d, J = 17.2 Hz, 1 H, 7-H), 4.28 (d, J =
11.6 Hz, 1 H, CH2O), 4.33 (d, J = 11.6 Hz, 1 H, CH2O), 6.01 (s, 1
H, 2-H), 7.16 (m, 4 H, H arom.) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 12.5, 17.1, 27.2, 33.4, 38.9, 57.4, 58.5, 66.9,
122.7, 126.2, 126.3, 126.8, 139.5, 141.7, 145.9, 148.5, 178.6 ppm.
MS (APCI): m/z = 285.3 [M + H]+.
[1] a) B. Bonnaud, P. Funes, N. Jubault, B. Vacher, Eur. J. Org.
Chem. 2005, 15, 3360–3369; b) D. B. Bylund, Br. J. Pharmacol.
2005, 144, 159–160; c) Only a single enantiomer is shown for
clarity, even though racemates were synthesized throughout
this work.
[2] R. W. Turner, T. Seden, J. Chem. Soc. Chem. Commun. 1966,
399; T. R. Potts, R. E. Harmon, J. Org. Chem. 1969, 34, 2792–
2793; L. Ghosez, R. Montaigne, A. Roussel, H. Vanlierde, P.
Mollet, Tetrahedron 1971, 27, 615–633; P. Doyle, R. H. B. Galt,
R. J. Pearce, Tetrahedron Lett. 1973, 2903–2904; L. R. Krepski,
A. Hassner, J. Org. Chem. 1978, 43, 2879–2882; P. W. Jeffs, G.
Molina, M. W. Cass, N. A. Cortese, J. Org. Chem. 1982, 47,
3871–3875; G. Mehta, H. S. P. Rao, Synth. Commun. 1985, 15,
991–1000; Y. L. Chen, K. Hedberg, Bioorg. Med. Chem.1991,
1, 47–50; Y. L. Chen, J. Nielsen, K. Hedberg, A. Dunaiskis, S.
Jones, L. Russo, J. Johnson, J. Ives, D. Liston, J. Med. Chem.
1992, 35, 1429–1434; Y. Strenstrom, Synth. Commun. 1992, 22,
2801–2810; W. Zhang, Y. Hua, G. Hoge, P. Dowd, Tetrahedron
Lett. 1994, 35, 3865–3868.
7a-(tert-Butylcarbonyloxymethyl)-1-endo,2a-dimethyl-1,2,2a,7-tetra-
hydrocyclobuta[a]indene (30-endo): Compound 34 (1.22 g,
0.77 mmol) in anhydrous EtOH (2 mL) was hydrogenated in the
presence of PtO2 (0.02 g) under a low pressure of hydrogen (bal-
loon). After 1.5 h, the catalyst was filtered off and the filtrate con-
centrated in vacuo to give 30 (0.20 g, 92%) (endo/exo Ͼ 95:5 as
1
determined by H NMR spectroscopy) as a colorless oil. Rf = 0.35
[cyclohexane/EtOAc (95:5)]. IR (film): ν = 1729 (C=O) cm–1
.
˜
1NMR (400 MHz, CDCl3, 25 °C): δ = 0.91 (d, J = 6.8 Hz, 3 H,
C1–CH3), 1.16 [s, 9 H, C(CH3)3], 1.36 (s, 3 H, 2a-CH3), 1.58 (m, 1
H, 2-H), 2.31 (m, 1 H, 2-H, 1-H), 2.89 (d, J = 17.2 Hz, 1 H, 7-H),
3.15 (d, J = 17.2 Hz, 1 H, 7-H), 4.17 (d, J = 11.2 Hz, 1 H, CH2O),
4.23 (d, J = 11.2 Hz, 1 H, CH2O), 7.14 (m, 4 H, H arom.) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 15.1, 16.4, 20.8, 27.1,
30.1, 36.0, 38.8, 41.2, 49.7, 50.8, 68.5, 122.3, 124.2, 126.5, 126.7,
143.0, 152.1, 178.7 ppm. MS (APCI): m/z = 287.3 [M + H]+.
[3] M. D. Lawlor, T. W. Lee, R. L. Danheiser, J. Org. Chem. 2000,
65, 4375–4384; R. L. Danheiser, I. Okamoto, M. D. Lawlor,
T. W. Lee, Org. Synth. 2003, 80, 160–171.
[4] For examples of polycyclic compounds containing a cyclobu-
tane ring not synthesized by a [2+2] cycloaddition, see: a) J. S.
Swenton, K. A. Burdett, D. M. Madigan, T. Johnson, P. D.
Rosso, J. Am. Chem. Soc. 1975, 97, 3428–3435; b) A. Padwa,
L. Precedo, M. A. Semones, J. Org. Chem. 1999, 64, 4079–
4088; G. Mehta, K. Sreenivas, Chem. Commun. 2001, 1892–
1893; K. Takasu, M. Ueno, K. Inanaga, M. Ihara, J. Org.
Chem. 2004, 69, 517–521; A. Rivkin, F. Gonzalez-Lopez de Tu-
riso, T. Nagashima, D. P. Curran, J. Org. Chem. 2004, 69,
3719–3725; S. J. Bader, M. L. Snapper, J. Am. Chem. Soc. 2005,
127, 1201–1205.
[5] a) We found few examples of cycloadditions of ketenes with
tri- and tetrasubstituted olefins but not with indenes: D. A.
Bak, W. T. Brady, J. Org. Chem. 1979, 44, 107–110. b) In ref.[5a]
it was reported that 1-methylcyclohexene gave a 4:1 mixture of
regioisomeric cyclobutanones in the [2+2] cycloaddition with
ketene.
[6] B. Ernst, A. de Mesmaeker, H. Greuter, S. J. Veenstra, “Intra-
molecular [2+2] Cycloadditions of Ketenes and Olefins” in
Strain and Its Implications in Organic Chemistry (Eds.: A.
de Meijere, S. Blechert), Kluwer Academic Publishers, Norwell,
MA, 1989, pp. 207–234; CNDO calculations (HyperChem, ver-
sion 5.1, Hypercube, Gainesville, USA) indicated that the
largest coefficient for the HOMO of styrenes 3a and 3b is on
the terminal carbon atom of the vinyl group. The [3.2.0] system
should therefore be favored over the [3.1.1] one.
[7] B. B. Snider, Chem. Rev. 1988, 88, 793–811; J. A. Hyatt, P. W.
Raynolds, “Ketene Cycloadditions” in Organic Reactions, vol.
45 (Ed.: L. A. Paquette), Wiley, New York, 1994, chapter 2,
pp. 162–646; P. M. Donate, R. Da Silva, G. Valdo, J. Da Silva,
C. Aleman, Synth. Commun. 2001, 31, 141–150.
2-(1-endo,2a-Dimethyl-1,2,2a,7-tetrahydrocyclobuta[a]inden-7a-yl)-
4,5-dihydro-1H-imidazole (1b-2-endo): Compound 1b-2-endo was
prepared from 38-endo as described for 1b-1. The crude product
was purified by silica gel chromatography eluting with CH2Cl2/
MeOH/NH4OH (95:5:0.5) to give 1b-2-endo (68%) as a white solid;
m.p. 106–107 °C. Rf = 0.17 [CH2Cl2/MeOH/NH4OH (90:9:1)]. IR
(KBr): ν = 3239 (NH), 1598 (C=N) cm–1. 1H NMR (400 MHz,
˜
CDCl3, 25 °C): δ = 1.04 (d, J = 7.1 Hz, 3 H, 1-CH3), 1.38 (s, 3 H,
2a-CH3), 1.60 (dd, J = 8.5, 11.3 Hz, 1 H, 2-H), 2.18 (dd, J = 9.6,
11.3 Hz, 1 H, 2-H), 3.20 (d, J = 17.6 Hz, 1 H, 7-H), 3.25 (m, 1 H,
1-H), 3.41 (d, J = 17.6 Hz, 1 H, 7-H), 3.51 (m, 2 H, H imidazoline),
3.60 (m, 2 H, H imidazoline), 7.09 (m, 1 H, H arom.), 7.18 (m, 2
H, H arom.), 7.25 (m, 1 H, H arom.) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 15.9, 20.3, 28.5, 36.3, 41.2, 46.9, 52.8, 53.6,
122.2, 124.6, 126.7, 126.9, 143.5, 150.5, 170.6 ppm. C16H20N2
(240.35): calcd. C 79.96, H 8.39, N 11.66; found C 79.85, H 8.35,
N 11.27. MS (ESI+): m/z = 241.1 [M + H]+.
2-(1-endo,2a-Dimethyl-1,2,2a,7-tetrahydrocyclobuta[a]inden-7a-yl)-
4,5-dihydro-1H-imidazole (1b-2-exo): Compound 1b-2-exo was pre-
pared from 38-exo as described for 1b-1. Rf = 0.20 [CH2Cl2/MeOH/
NH4OH (90:9:1)]. 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.06
(d, J = 6.8 Hz, 3 H, 1-CH3), 1.43 (s, 3 H, 2a-CH3), 2.01 (t, J =
10.4 Hz, 1 H, 2-H), 2.19 (t, J = 12.0 Hz, 1 H, 2-H), 2.29 (m, 1 H,
1-H), 2.97 (d, J = 16.0 Hz, 1 H, 7-H), 3.46 (d, J = 16.0 Hz, 1 H,
7-H), 3.65 (br. s, 4 H, H imidazoline), 7.19–7.26 (4 H, H arom.)
ppm.13C NMR (100 MHz, CDCl3, 25 °C): δ = 15.3, 22.9, 35.6,
41.6, 42.4, 49.6, 51.9, 55.9, 123.6, 125.0, 126.8, 126.9, 140.9, 151.4,
167.8 ppm. MS (ESI+): m/z = 241.1 [M + H]+.
[8] K. Shishido, T. Azuma, M. Shibuya, Tetrahedron Lett. 1990,
31, 219–220.
[9] a) W. Guangzhong, I. Shimoyama, E.-I. Negishi, J. Org. Chem.
1991, 56, 6506–6507. The authors described a [2+2] cycload-
dition between an arylketene and a homobenzylic alkene which
Supporting Information Available (see footnote on the first page of
this aricle): Experimental and analytical data for compounds 2a,
254
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 246–256