2776
S. H. Kim et al. / Tetrahedron Letters 51 (2010) 2774–2777
H
N
H
N
H
N
H
N
Ph
CF3
H
CH3
O
O
O
O
CN
CN
CN
CN
Me
Me
1j
1h
(sluggish reaction)
1i
(sluggish reaction)
1k
(complex mixture)
O
(sluggish reaction)
O
Ph
H
Ph
H
N
N
O
Me
L
L
In
In
N
N
Me
L
L
Me
1g
1h
sterically more congested than 1g
sterically less hindered than 1h
Figure 1.
H
N
H
O
H
N
2nd
allylation
allyl bromide (4.0 equiv)
In (2.0 equiv), THF
N
O
OEt
NH
N
O
reflux, 60 min
CN
3
4 (88%)
1st
allylation
- EtOH
H
N
H
N
N
OEt
OH
- H2O
COOEt
NH
OEt
N
N
Scheme 4.
Tseng, B.; Drewe, J.; Cai, S. X. J. Med. Chem. 2009, 52, 2341–2351; (f) Henderson,
E. A.; Bavetsias, V.; Theti, D. S.; Wilson, S. C.; Clauss, R.; Jackman, A. L. Bioorg.
Med. Chem. 2006, 14, 5020–5042.
Acknowledgments
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (2009-
0070633). Spectroscopic data were obtained from the Korea Basic
Science Institute, Gwangju branch.
5. For the synthesis of quinazoline derivatives, see: (a) Connolly, D. J.; Cusack, D.;
O’Sullivan, T. P.; Guiry, P. J. Tetrahedron 2005, 61, 10153–10202. and further
references cited therein; (b) Truong, V. L.; Morrow, M. Tetrahedron Lett. 2010, 51,
758–760; (c) Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 14254–
14255; (d) Bergman, J.; Brynolf, A.; Elman, B.; Vuorinen, E. Tetrahedron 1986, 42,
3697–3706; (e) Gupta, S.; Agarwal, P. K.; Kundu, B. Tetrahedron Lett. 2010, 51,
1887–1890; (f) Kotsuki, H.; Sakai, H.; Morimoto, H.; Suenaga, H. Synlett 1999,
1993–1995; (g) Yoon, D. S.; Han, Y.; Stark, T. M.; Haber, J. C.; Gregg, B. T.;
Stankovich, S. B. Org. Lett. 2004, 6, 4775–4778; (h) Ferrini, S.; Ponticelli, F.;
Taddei, M. Org. Lett. 2007, 9, 69–72; (i) de Fatima Pereira, M.; Alexandre, F. R.;
Thiery, V.; Besson, T. Tetrahedron Lett. 2004, 45, 3097–3099; (j) Larksarp, C.;
Alper, H. J. Org. Chem. 2000, 65, 2773–2777; (k) Mizuno, T.; Okamoto, N.; Ito, T.;
Miyata, T. Tetrahedron Lett. 2000, 41, 1051–1053; (l) Szczepankiewicz, W.;
Suwinski, J.; Bujok, R. Tetrahedron 2000, 56, 9343–9349; (m) Hioki, H.;
Matsushita, K.; Nakamura, S.; Horiuchi, H.; Kubo, M.; Harada, K.; Fukuyama, Y.
J. Comb. Chem. 2008, 10, 620–623.
References and notes
1. For the general review on indium-mediated reactions, see: (a) Auge, J.; Lubin-
Germain, N.; Uziel, J. Synthesis 2007, 1739–1764; (b) Kargbo, R. B.; Cook, G. R.
Curr. Org. Chem. 2007, 11, 1287–1309; (c) Lee, P. H. Bull. Korean Chem. Soc. 2007,
28, 17–28; (d) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149–11176; (e) Pae,
A. N.; Cho, Y. S. Curr. Org. Chem. 2002, 6, 715–737; (f) Nair, V.; Ros, S.; Jayan, C.
N.; Pillai, B. S. Tetrahedron 2004, 60, 1959–1982; (g) Podlech, J.; Maier, T. C.
Synthesis 2003, 633–655.
2. (a) Fujiwara, N.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 4729–4732; (b)
Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1999, 64, 4095–4101; For diallylation of
benzonitrile with allylindate, see: (c) Jin, S.-J.; Araki, S.; Butsugan, Y. Bull. Chem.
Soc. Jpn. 1993, 66, 1528–1532; For the indium(I) iodide-promoted allylation of
6. The starting materials 1a–i and 1k were prepared from the corresponding 2-
aminoarylcarbonitriles and benzoic anhydride, pivalic anhydride, trifluoroacetic
anhydride, or acetic anhydride. Compound 1j was prepared with formic acid.
Compound 3 was prepared from 2-aminobenzonitrile and ethyl chloroformate.
7. Typical procedure for the synthesis of 2a: A stirred mixture of 1a (111 mg,
0.5 mmol), allyl bromide (121 mg, 1.0 mmol), and indium (57 mg, 0.5 mmol) in
THF (1.0 mL) was heated to reflux for 60 min. After the usual aqueous workup
and column chromatographic purification process (hexanes/CH2Cl2/EtOAc,
15:1:1), we obtained compound 2a (88 mg, 71%) as colorless oil. Other
compounds were synthesized similarly, and the selected spectroscopic data of
2a–c, 2g, 2a0, and 4 are as follows.
a
,b-unsaturated nitrile, see: (d) Ranu, B. C.; Das, A. Tetrahedron Lett. 2004, 45,
6875–6877.
3. For the In-mediated Barbier type allylation of nitrile-containing substrates, see:
(a) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 1696–
1698; (b) Kim, S. H.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2009, 50,
5744–5747; (c) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2009,
50, 6476–6479; (d) Kim, S. H.; Kim, S. H.; Kim, K. H.; Kim, J. N. Tetrahedron Lett.
2010, 51, 860–862.
4. For the synthesis and biological activities of natural and non-natural quinazoline
derivatives, see: (a) Mason, J. J.; Bergman, J. Org. Biomol. Chem. 2007, 5, 2486–
2490; (b) Xin, Z. H.; Fang, Y.; Du, L.; Zhu, T.; Duan, L.; Chen, J.; Gu, Q.-Q.; Zhu, W.-
M. J. Nat. Prod. 2007, 70, 853–855; (c) Gellibert, F.; Fouchet, M.-H.; Nguyen, V.-L.;
Wang, R.; Krysa, G.; de Gouville, A.-C.; Huet, S.; Dodic, N. Bioorg. Med. Chem. Lett.
2009, 19, 2277–2281; (d) Gong, G.; Xie, Y.; Liu, Y.; Rinderspacher, A.; Deng, S.-X.;
Feng, Y.; Zhu, Z.; Tang, Y.; Wyler, M.; Aulner, N.; Toebben, U.; Smith, D. H.;
Branden, L.; Chung, C.; Schurer, S.; Vidovic, D.; Landry, D. W. Bioorg. Med. Chem.
Lett. 2009, 19, 1191–1194; (e) Sirisoma, N.; Pervin, A.; Zhang, H.; Jiang, S.;
Willardsen, J. A.; Anderson, M. B.; Mather, G.; Pleiman, C. M.; Kasibhatla, S.;
Compound 2a: 71%; colorless oil; IR (film) 1568, 1548, 1491, 1344 cmꢀ1 1H NMR
;
(CDCl3, 300 MHz) d 4.09 (dt, J = 6.6 and 1.5 Hz, 2H), 5.18–5.28 (m, 2H), 6.22–6.35
(m, 1H), 7.47–7.55 (m, 4H), 7.81 (ddd, J = 8.4, 6.9 and 1.5 Hz, 1H), 8.04–8.08 (m,
2H), 8.63–8.66 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 39.51, 117.50, 122.36,
124.69, 126.82, 128.47, 128.56, 129.34, 130.38, 133.39, 134.16, 138.23, 150.81,
160.16, 168.89; ESIMS m/z 247 (M++1). Anal. Calcd for C17H14N2: C, 82.90; H,
5.73; N, 11.37. Found: C, 82.65; H, 5.94; N, 11.18.
Compound 2b: 69%; colorless oil; IR (film) 2957, 1574, 1559, 1494, 1390 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 1.50 (s, 9H), 4.02 (dt, J = 6.6 and 1.5 Hz, 2H), 5.13–
5.23 (m, 2H), 6.17–6.30 (m, 1H), 7.50 (ddd, J = 8.4, 6.9 and 1.2 Hz, 1H), 7.78 (ddd,
J = 8.4, 6.9 and 1.5 Hz, 1H), 7.98 (dq, J = 8.4 and 0.6 Hz, 1H), 8.04 (dq, J = 8.4 and
0.6 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 29.57, 39.33, 39.47, 117.01, 121.59,
124.40, 126.27, 129.09, 132.76, 134.54, 150.23, 167.96, 172.78; ESIMS m/z 227