6212
J. Tan et al. / Tetrahedron 67 (2011) 6206e6213
(m, 2H), 6.91e6.93 (m, 2H), 6.64e6.66 (m, 2H), 6.57e6.59 (m, 2H),
4.43 (dd, J¼3.0, 8.4 Hz, 1H), 3.83 (s, 3H), 3.81 (br, 2H), 3.42 (dd,
J¼3.1, 11.0 Hz, 1H), 3.31 (dd, J¼8.3, 11.0 Hz, 1H); 13C NMR
substrate (0.5 mmol), and HCOONa (340 mg, 5 mmol) in an aqueous
solution of HOAc/NaOAc (5 M, 5 mL, pH¼5.5 or pH¼4.3 with 0.3 mL
EtOAc) was sealed without degassing. The reaction mixture was
stirred at 40 ꢀC for the time indicated, then cooled to room tem-
perature and basified with an aqueous solution of KOH. The
resulting mixture was extracted with diethyl ether (3ꢂ5 mL) and
dried over Na2SO4. The solvent was removed under reduced pres-
sure, and the product was purified by flash column chromatogra-
phy. The ee was determined by HPLC with an OD-H chiral column.
(100.6 MHz, CDCl3)
d 160.2, 135.1, 134.8, 133.8, 129.0, 119.7, 119.6,
115.5, 115.3, 114.9, 56.2, 55.0, 50.2; HRMS (ESI) calcd for
C15H17N2O[MþH]þ: 241.1335, found: 241.1339.
4.4.16. 2-(2-Methoxyphenyl)-tetrahydroquinoxaline (2p)5g. Yellow
solid, mp 124e126 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.41e7.44 (m,
1H), 7.27e7.30 (m, 1H), 6.89e6.99 (m, 2H), 6.56e6.66 (m, 4H), 4.92
(dd, J¼2.8, 7.0 Hz, 1H), 3.83 (br, 2H), 3.86 (s, 3H), 3.55 (dd, J¼3.0,
10.9 Hz, 1H), 3.29 (dd, J¼7.1, 11.0 Hz, 1H); 13C NMR (100.6 MHz,
Acknowledgements
CDCl3)
d 157.3, 135.2, 133.8, 130.9, 129.2, 127.8, 121.6, 119.7, 119.3,
Financial support from the National Natural Science Foundation
of China (20873179 and 20910102051), Renmin University of China
and Institute of Chemistry, the Chinese Academy of Sciences is
greatly acknowledged.
115.6, 115.3, 111.0, 56.1, 48.6, 47.5; HRMS (ESI) calcd for C15H17N2O
[MþH]þ: 241.1335, found: 241.1338.
4.4.17. 2-p-Tolyl-1,2,3,4-tetrahydroquinoxaline(2q)5j. Yellow solid,
mp 98e100 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.27e7.29 (m, 2H),
References and notes
7.18e7.20 (m, 2H), 6.62e6.65 (m, 2H), 6.56e6.59 (m, 2H), 4.45 (dd,
J¼2.3, 8.0 Hz, 1H), 3.82 (br, 2H), 3.44 (dd, J¼2.8, 11.0 Hz, 1H),
3.29e3.34 (m, 1H), 2.36 (s, 3H); 13C NMR (100.6 MHz, CDCl3)
1. (a) Benkovic, S. J.; Benkovic, P. A.; Comfort, D. R. J. Am. Chem. Soc. 1969, 91, 5270;
(b) Mertes, M. P.; Lin, A. J. J. Med. Chem. 1970, 13, 77; (c) Jacobsen, E. J.; Stelzer, L.
S.; Belonga, K. L.; Carter, D. B.; Im, W. B.; Sethy, V. H.; Tang, A. H.; VonVoigt-
lander, P. F.; Petke, J. D. J. Med. Chem. 1996, 39, 3820; (d) Sikorski, J. A. J. Med.
Chem. 2006, 49, 1; (e) Ohtake, Y.; Naito, A.; Hasegawa, H.; Kawano, K.; Mor-
izono, D.; Tangiguchi, M.; Tanka, Y.; Matsukwa, H.; Naito, K.; Oguma, T.; Ezure,
Y.; Tsuriya, Y. Bioorg. Med. Chem. 1999, 7, 1247; (f) Torisu, K.; Kobayashi, K.;
Iwahashi, M.; Nakai, Y.; Onoda, T.; Nagase, T.; Sugimoto, I.; Okada, Y.; Matsu-
moto, R.; Nanbu, F.; Ohuchida, S.; Nakai, H.; Toda, M. Bioorg. Med. Chem. 2004,
12, 5361; (g) Eary, C. T.; Jones, Z. S.; Groneberg, R. D.; Burgess, L. E.; Mareska, D.
A.; Drew, M. D.; Blake, J. F.; Laird, E. R.; Balachari, D.; O’sullivan, M.; Allen, A.;
Marsh, V. Bioorg. Med. Chem. Lett. 2007, 17, 2608; (h) Gluchowski, C. Eur. Pat. EP
0422878 A1, 2004; (i) Jones, Z.; Groneberg, R.; Drew, M.; Eary, C. T. U.S. Patent
20050282812 2005.
2. (a) Chandrasekaran, Y.; Dutta, G. K.; Kanth, B. R.; Patil, S. Dyes and Pigments
2009, 83, 162; (b) Satam, V.; Rajule, R.; Bendre, S.; Bineesh, P.; Kanetkar, V. J.
Heterocycl. Chem. 2009, 46, 221; (c) Wojcik, A.; Nicolaescu, R.; Kamat, P. V.;
Chandrasekaran, Y.; Patil, S. J. Phys. Chem. A 2010, 114, 2744.
3. (a) DeSelms, R. C.; Mosher, H. S. J. Am. Chem. Soc. 1960, 82, 3762; (b) Rao, K. V.;
Jackman, D. J. J. Heterocycl. Chem. 1973, 10, 213; (c) Armand, J.; Chekir, K. J.
Heterocycl. Chem. 1980, 17, 1237; (d) Moody, C. J.; Pitts, M. R. Synlett 1998, 1029;
(e) McKinney, A. M.; Jackson, K. R.; Salvatore, R. N.; Savrides, E.-M.; Edattel, M.
J.; Gavin, T. J. Heterocycl. Chem. 2005, 42, 1031.
d
139.8, 138.6, 135.2, 133.8, 130.3, 127.9, 119.9, 119.7, 115.7, 115.4,
55.4, 50.2, 22.1; HRMS (ESI) calcd for C15H17N2[MþH]þ: 225.1386,
found: 225.1391.
4.4.18. 2-(Biphenyl-4-yl)-1,2,3,4-tetrahydroquinoxaline(2r). Yellow
solid, mp 184e186 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.59e7.60 (m,
4H), 7.44e7.48 (m, 4H), 7.34e7.38 (m, 1H), 6.65e6.68 (m, 2H),
6.60e6.66 (m, 2H), 4.54 (dd, J¼2.9, 8.0 Hz, 1H), 3.90 (br, 2H), 3.51
(dd, J¼3.0, 11.0 Hz, 1H), 3.37 (dd, J¼8.0, 11.0 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3)
d 141.9, 141.8, 141.7, 135.0, 133.8, 130.0, 128.4,
128.3, 128.1, 127.8, 120.0, 119.8, 115.7, 115.4, 55.4, 50.0; HRMS (ESI)
calcd for C20H19N2[MþH]þ: 287.1543, found: 287.1549.
4.4.19. 2-Styryltetrahydroquinoxaline (2s)5g. Yellow solid, mp
110e111 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.26e7.41 (m, 5H),
6.55e6.69 (m, 5H), 6.26 (dd, J¼8.4, 15.9 Hz, 1H), 4.09e4.14 (m, 1H),
4. (a) Cavagnol, J. C.; Wiselogle, F. Y. J. Am. Chem. Soc. 1947, 69, 795; (b) DeSelms, R.
C.; Greaves, R. J.; Schleigh, W. R. J. Heterocycl. Chem. 1974, 11, 595.
3.71 (br, 2H), 3.42 (dd, J¼3.0, 10.8 Hz, 1H), 3.23 (dd, J¼7.5, 10.8 Hz,
1H); 13C NMR (100.6 MHz, CDCl3)
d 137.3, 133.9, 133.8, 132.4, 130.0,
5. (a) Murata, S.; Sugimoto, T.; Matsuura, S. Heterocycles 1987, 26, 763; (b) Bian-
chini, C.; Barbaro, P.; Scapacci, G.; Farnetti, E.; Graziani, M. Organometallics
1998, 17, 3308; (c) Bianchini, C.; Barbaro, P.; Scapacci, G. J. Organomet. Chem.
2001, 621, 26; (d) Cobley, C. J.; Henschke, J. P. Adv. Synth. Catal. 2003, 345, 195;
(e) Henschke, J. P.; Burk, M. J.; Malan, C. G.; Herzberg, D.; Peterson, J. A.;
Wildsmith, A. J.; Cobley, C. J.; Casy, G. Adv. Synth. Catal. 2003, 345, 300; (f) Qiu,
L.; Kwong, F.; Wu, J.; Lam, W.; Chan, S.; Yu, W.; Li, Y.; Guo, R.; Zhou, Z.; Chan, A.
S. C. J. Am. Chem. Soc. 2006, 128, 5955; (g) Tang, W.; Xu, L.; Fan, Q.; Wang, J.; Fan,
B.; Zhou, Z.; Lam, K.; Chan, A. S. C. Angew. Chem., Int. Ed. 2009, 48, 9135; (h)
Mrsic, N.; Jerphagnon, T.; Minnaard, A. J.; Feringa, B. L.; de Vries, J. G. Adv. Synth.
Catal. 2009, 351, 2549; (i) Wang, D.-S.; Zhou, Y.-G. Tetrahedron Lett. 2010, 51,
3014; (j) Cartigny, D.; Nagano, T.; Ayad, T.; Gnent, J.-P.; Ohshima, T.; Mashima,
K.; Ratovelomanana-Vidal, V. Adv. Synth. Catal. 2010, 352, 1886.
129.4, 128.6, 127.3, 119.8, 119.6, 115.4, 115.4, 53.6, 47.6; HRMS (ESI)
calcd for C16H17N2 [MþH]þ: 237.1386, found: 237.1391.
4.4.20. 2-(20-Chloro-styryl)tetrahydroquinoxaline(2t)5g. Yellow solid,
mp 118e119 ꢀC;1HNMR(400MHz,CDCl3)
d
7.54(d, J¼7.4Hz,1H), 7.35
(d, J¼1.7Hz,1H), 7.20e7.22(m, 2H), 7.06(d, J¼15.8,1H), 6.55e6.64 (m,
4H), 6.27 (dd, J¼8.2,15.9 Hz,1H), 4.14e4.19 (m,1H), 3.61 (br, 2H), 3.51
(dd, J¼2.9, 10.9 Hz, 1H), 3.31 (dd, J¼7.2, 10.8 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3)
d 135.4, 133.9, 133.7, 133.6, 132.9, 130.5, 129.6,
128.5,127.7,127.6,119.8,119.7,115.4,115.3,53.6, 47.5;HRMS(ESI)calcd
6. (a) Yang, S. C.; Liu, P. C.; Febg, W. H. Tetrahedron Lett. 2004, 45, 4951; (b) Yang, S.
C.; Shue, Y. J.; Liu, P. C. Organometallics 2002, 21, 2013; (c) Massacret, M.; Lhoste,
P.; Sinou, D. Eur. J. Org. Chem. 1999, 129.
for C16H16ClN2 [MþH]þ: 271.0997, found: 271.1000.
7. Nair, V.; Dhanya, R.; Rajesh, C.; Bhadbhade, M. M.; Manoj, K. Org. Lett. 2004, 6,
4743.
8. Eary, C. T.; Clausen, D. Tetrahedron Lett. 2006, 47, 6899.
4.4.21. 2-(30-Nitro-styryl)tetrahydroquinoxaline(2u)5g. Red oil; 1H
NMR (400 MHz, CDCl3) d 8.23e8.24 (m, 1H), 8.07e8.10 (m, 1H), 7.68
9. (a) Merisor, E.; Conrad, J.; Mike, S.; Beifuss, U. Synlett 2007, 2033; (b) LaBarbera,
D. V.; Skibo, E. B. Bioorg. Med. Chem. 2005, 13, 387; (c) Bunce, R. A.; Herron, D.
M.; Hale, L. Y. J. Heterocycl. Chem. 2003, 40, 1031; (d) Krchnak, V.; Smith, J.;
Vagner, J. Tetrahedron Lett. 2001, 42, 2433; (e) Bunce, R. A.; Herron, D. M.; Ac-
kerman, M. L. J. Org. Chem. 2000, 65, 2847.
10. For reviews, see: (a) Brieger, G.; Nestrick, T. J. Chem. Rev. 1974, 74, 567; (b)
Johnstone, R. A. W.; Wilby, A. H.; Entwistle, I. D. Chem. Rev. 1985, 85, 129; (c)
Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97; (d) Gladiali, S.; Alberico, E.
Chem. Soc. Rev. 2006, 35, 226; (e) Ikariya, T.; Blacker, A. J. Acc. Chem. Res. 2007,
40, 1300; (f) Wang, C.; Wu, X.; Xiao, J. Chem. Asian J. 2008, 3, 1750.
(d, J¼7.7 Hz, 1H), 7.46e7.50 (m, 1H), 6.61 (d, J¼15.9 Hz, 1H),
6.63e6.65 (m, 2H), 6.55e6.58 (m, 2H), 6.45 (dd, J¼8.8, 15.9 Hz, 1H),
4.16e4.18 (m, 1H), 3.76 (br, 2H), 3.51 (dd, J¼3.1, 10.9 Hz, 1H), 3.29
(dd, J¼6.7, 11.0 Hz, 1H); 13C NMR (100.6 MHz, CDCl3)
d 149.3, 139.2,
133.7, 133.6, 133.5, 133.1, 130.3, 129.9, 123.0, 121.8, 119.8, 119.6, 115.5,
115.3, 53.3, 47.2; HRMS (ESI) calcd for C16H16N3O2 [MþH]þ:
282.1237, found: 282.1244.
11. (a) Watanabe, Y.; Ohta, T.; Tsuji, Y.; Hiyoshi, T.; Tsuji, Y. Bull. Chem. Soc. Jpn. 1984,
57, 2440; (b) Balczewski, P.; Joule, J. A. Synth. Commun. 1990, 20, 2815; (c) Za-
charie, B.; Moreau, N.; Dockendorff, C. J. Org. Chem. 2001, 66, 5264; (d) Fujita, K.;
Kitatsuji, C.; Fulukawa, S.; Yamaguchi, R. Tetrahedron Lett. 2004, 45, 3215; (e)
Frediani, P.; Rosi, L.; Cetarini, L.; Frediani, M. Inorg. Chim. Acta 2006, 359, 2650;
(f) Voutchkova, A. M.; Gnanamgari, D.; Jakobsche, C. E.; Butler, C.; Miller, S. T.;
Parr, J.; Crabtree, R. H. J. Organomet. Chem. 2008, 693, 1815; (g) Wang, C.; Li, C.;
4.5. General procedure for asymmetric transfer
hydrogenation of quinoxalines
A carousel reaction tube containing a magnetic stirring bar and
metal precursor (2.5 mmol), ligand 3h (2.5 mg, 6 mmol), quinoxaline