RuII-Catalyzed [2+2] Cycloadditions
Cycloadduct 5b. General Method B: (Table 1, Entry 6). Norbornene
2b (82.4 mg, 0.541 mmol), acetylene 4 (20.0 mg, 0.115 mmol), Et3N
(0.10 + 0.05 mL), Cp*RuCl(COD) (7.2 mg, 0.019 mmol) were used.
The solution was stirred in the darkness for 35 min at 85 °C. Al-
kyne 4 was added over an 2 h at 85 °C. The reaction was stirred
for an additional 23 h min at 85 °C. The crude product was purified
by column chromatography (EtOAc/hexanes, 0:1, 1:19, 1:9) to give
the cycloadduct 5b (26.5 mg, 0.081 mmol, 71%) as a white solid. Rf
= 0.23 (EtOAc/hexanes, 1:9); m.p. 84–85.5 °C. GC (HP-1 column):
the cycloadduct 5e (29.6 mg, 0.086 mmol, 90%) as a white solid.
Rf = 0.45 (EtOAc/hexanes, 1:9); m.p. 79–80 °C. GC (HP-1 column):
retention time 21.650 min. IR (CH Cl ): νmax = 2955 (s), 2871 (w),
˜
2
2
1700 (s), 1614 (m), 1492 (m), 1448 (m), 1212 (s), 1189 (s), 1132 (m)
1
cm–1. H NMR (CDCl3, 400 MHz): δ = 8.09 (m, 2 H), 7.41 (m, 3
H), 7.23 (J = 6.9 Hz, d 2 H, 2 H), 7.21 (t, J = 6.9 Hz, 2 H), 7.14
(t, J = 6.9 Hz, 1 H), 4.29 (q, J = 7.1 Hz, 2 H), 3.03 (d, J = 3.7 Hz,
1 H), 3.02 (s, 1 H), 2.92 (d, J = 3.7 Hz, 1 H), 2.71 (br. s, 1 H), 2.67
(br. s, 1 H), 1.63 (dm, J = 9.2 Hz, 2 H), 1.38 (t, J = 7.1 Hz, 3 H),
1.22 (dm, J = 9.2 Hz, 2 H) ppm. 13C NMR (APT, CDCl3,
retention time 18.379 min. IR (CH Cl ): νmax = 3065 (m), 2973 (s),
˜
2
2
2876 (m), 1738 (s), 1703 (s), 1615 (m), 1492 (m), 1367 (m), 1246 100 MHz): δ = 163.0, 155.2, 141.0, 132.5, 130.0, 128.9, 128.38,
(s), 1220 (s), 1199 (s), 1078 (m) cm–1. 1H NMR (CDCl3, 400 MHz):
δ = 8.02 (m, 2 H), 7.38 (m, 3 H), 4.85 (s, 1 H), 4.26 (mABX, 3 H),
128.35, 128.0, 127.5, 125.5, 60.1, 47.2, 46.7, 45.2, 37.9, 37.5, 26.42,
26.41, 14.4 ppm. C24H24O2: C 83.69, H 7.02; found C 83.85, H
2.93 (d, J = 4.0 Hz, 1 H), 2.84 (d, J = 4.0 Hz, 1 H), 2.47 (br. s, 1 7.14.
H), 2.43 (br. s, 1 H), 1.99 (s, 3 H), 1.88 (dd, J = 10.1, 3.2 Hz, 2 H),
Supporting Information (see also the footnote on the first page of
1.34 (t, J = 7.1 Hz, 3 H), 1.32 (d, J = 10.1 Hz, 2 H) ppm. 13C NMR
(APT, CDCl3, 100 MHz): δ = 170.6, 162.6, 154.9, 132.2, 130.2,
128.9, 128.4, 128.1, 79.1, 60.2, 45.4, 44.9, 37.1, 36.7, 26.2, 26.1,
21.1, 14.3 ppm. C20H22O4: C 73.60, H 6.79; found C 73.44, H 6.89.
1
this article): H and 13C NMR spectra of all new compounds.
Acknowledgments
Cycloadduct 5c. General Method B: (Table 1, Entry 8). Norbornene
2c (86.5 mg, 0.520 mmol), acetylene 4 (20.5 mg, 0.118 mmol), THF
(0.05 + 0.06 mL), Cp*RuCl(COD) (5.1 mg, 0.013 mmol) were used.
The solution was stirred in the darkness for 30 min at 60 °C. The
alkyne 4 was added over a 1 h 60 °C. The reaction was stirred for an
additional 2 h at 60 °C. The crude product was purified by column
chromatography (EtOAc/hexanes, 0:1, 1:19) to give the cycloadduct
5c (36.1 mg, 0.106 mmol, 90%) as a white solid. Rf = 0.43 (EtOAc/
hexanes, 1:9); m.p. 95–95.5 °C. GC (HP-1 column): retention time
We thank Merck Frosst Centre for Therapeutic Research, Boehr-
inger Ingelheim (Canada) Ltd., the Natural Sciences and Engineer-
ing Research Council of Canada (NSERC) and the University of
Guelph for the financial support of our program. R. W. J and P. L
thank the Ontario government and NSERC (Canada) for postgrad-
uate scholarships.
[1] For reviews on transition metal-catalyzed cycloadditions, see:
a) M. Lautens, W. Klute, W. Tam, Chem. Rev. 1996, 96, 49–92;
b) L. S. Hegedus, Coord. Chem. Rev. 1997, 161, 129–255; c)
P. A. Wender, J. A. Love, in Advances in Cycloaddition, JAI
Press, Greenwich, 1999, vol. 5, pp. 1–45.
[2] Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Flem-
ing, L. A. Paquette), vol. 5, chapters 2.1–2.6, Pergamon, Ox-
ford, 1991.
[3] a) T. Mitsudo, K. Kokuryo, T. Shinsugi, Y. Nakagawa, Y. Wat-
anabe, Y. Takegami, J. Org. Chem. 1979, 44, 4492–4496; b) T.
Mitsudo, H. Naruse, Y. Hori, Y. Watanabe, J. Organomet.
Chem. 1987, 334, 157–167; c) T. Mitsudo, H. Naruse, T.
Kondo, Y. Ozaki, Y. Watanabe, Angew. Chem. Int. Ed. Engl.
1994, 33, 580–581; d) T. Mitsudo, K. Kokuryo, T. Yoshinobu,
J. Chem. Soc. Chem. Commun. 1976, 722–723.
17.127 min. IR (CH Cl ): νmax = 3056 (m), 2975 (s), 2872 (w), 1701
˜
2
2
(s), 1615 (m), 1447 (m), 1265 (s), 1197 (m), 1111 (w) cm-1 cm–1.
1H NMR (CDCl3, 400 MHz): δ = 8.03 (m, 2 H), 7.38 (m, 3 H),
4.26 (mABX, 2 H), 3.82 (s, 1 H), 2.82 (d, J = 3.9 Hz, 1 H), 2.74 (d,
J = 3.9 Hz, 1 H), 2.15 (s, 1 H), 2.10 (s, 1 H), 1.94 (dm, J = 9.4 Hz,
2 H), 1.33 (t, J = 7.1 Hz, 3 H), 1.18 (dm, J = 8.4 Hz, 2 H), 1.06 (s,
9 H) ppm. 13C NMR (APT, CDCl3, 100 MHz): δ = 162.9, 155.3,
132.6, 129.9, 128.8, 128.4, 128.2, 75.2, 73.0, 60.0, 45.7, 45.2, 39.0,
38.4, 28.4, 26.6, 26.5, 14.4 ppm. C22H28O3: C 77.61, H 8.29; found
C 77.48, H 8.38.
Cycloadduct 5d. General Procedure B: (Table 1, Entry 10). Norbor-
nene 2d (36.6 mg, 0.389 mmol), acetylene 4 (19.9 mg, 0.114 mmol),
THF (0.06 + 0.06 mL), Cp*RuCl(COD) (2.9 mg, 0.008 mmol) were
used. The solution was stirred in the darkness for 35 min at 60 °C.
Alkyne 4 was added over 45 min at 60 °C. The reaction was stirred
for an additional 2 h 15 min at 60 °C. The crude product was puri-
fied by column chromatography (EtOAc/hexanes, 0:1, 1:19) to give
the cycloadduct 5d (29.1 mg, 0.108 mmol, 95%) as colourless oil. Rf
= 0.33 (EtOAc/hexanes, 1:19). GC (HP-1 column): retention time
[4] B. M. Trost, M. Yanai, K. Hoogsteen, J. Am. Chem. Soc. 1993,
115, 5294–5295.
[5] C. S. Yi, D. W. Lee, Y. Chen, Organometallics 1999, 18, 2043–
2045.
[6] a) D.-J. Huang, D. K. Rayabarapu, L.-P. Li, T. Sambaiah, C.-
H. Cheng, Chem. Eur. J. 2000, 6, 3706–3713; b) K. C. Chao,
D. K. Rayabarapu, C.-C. Wang, C.-H. Cheng, J. Org. Chem.
2001, 66, 8804–8810.
1
15.958 min. H NMR (CDCl3, 400 MHz): δ = 8.03 (m, 2 H), 7.37
[7] A. Tenaglia, L. Giordano, Synlett 2003, 2333–2336.
[8] a) R. W. Jordan, W. Tam, Org. Lett. 2000, 2, 3031–3034; b)
R. W. Jordan, W. Tam, Org. Lett. 2001, 3, 2367–2370; c) R. W.
Jordan, W. Tam, Tetrahedron Lett. 2002, 43, 6051–6054; d) K.
Villeneuve, R. W. Jordan, W. Tam, Synlett 2003, 2123–2128; e)
K. Villeneuve, W. Tam, Angew. Chem. Int. Ed. 2004, 43, 610–
613; f) K. Villeneuve, N. G. Riddell, R. W. Jordan, G. C. Tsui,
W. Ta m , Org. Lett. 2004, 6, 4543–4546; g) R. W. Jordan, P. R.
Khoury, J. D. Goddard, W. Tam, J. Org. Chem. 2004, 69, 8467–
8474; h) N. G. Riddell, K. Villeneuve, W. Tam, Org. Lett. 2005,
7, 3681–3684; i) N. G. Riddell, W. Tam, J. Org. Chem. 2006,
71, 1934–1937; j) P. Liu, R. W. Jordan, J. D. Goddard, W. Tam,
J. Org. Chem. 2006, 71, 3793–3803; k) R. W. Jordan, K. Vil-
leneuve, W. Tam, J. Org. Chem. 2006, 71, 5830–5833; l) R. R.
Burton, W. Tam, Tetrahedron Lett. 2006, 47, 7185–7189.
[9] R. B. Woodward, R. Hoffmann, The Conservation of Orbital
Symmetry, Academic Press, New York, 1970.
(m, 3 H), 4.25 (mABX, 2 H), 2.80 (d, J = 3.6 Hz, 1 H), 2.70 (d, J =
3.6 Hz, 1 H), 2.27 (d, J = 1.1 Hz, 1 H), 2.24 (d, J = 1.1 Hz, 1 H),
1.63 (m, 2 H),1.40 (dm, J = 10.4 Hz, 1 H), 1.34 (t, J = 7.1 Hz, 3
H), 1.20 (m, 2 H), 1.04 (dt, J = 10.4, 1.1 Hz, 1 H) ppm. 13C NMR
(APT, CDCl3, 100 MHz): δ = 163.1, 155.6, 132.7, 129.8, 128.8,
128.7, 128.3, 59.9, 46.5, 46.0, 34.7, 34.2, 30.6, 28.33, 28.32, 14.3
ppm. This is a known compound in the literature.[3c]
Cycloadduct 5e. General Method B: (Table 1, Entry 12). Norbor-
nene 2e (58.7 mg, 0.345 mmol), acetylene 4 (16.7 mg, 0.096 mmol),
THF (0.05 + 0.06 mL), and Cp*RuCl(COD) (3.4 mg, 0.009 mmol)
were used. The solution was premixed in the darkness for 25 min
at 60 °C. Alkyne 4 was added over a 1 h at 60 °C. The reaction was
stirred for an additional 2 h at 60 °C. The crude product was puri-
fied by column chromatography (EtOAc/hexanes, 0:1, 1:19) to give
Eur. J. Org. Chem. 2008, 80–86
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
85