Table 3 Synthesis of optically active 2,3-dihydro-1H-pyrazoles
(R)- or (S)-4
Entry
R1
R2
ee (%)
Ar
Yield of (R)- or (S)-5a (%)
eeb (%)
1
2
3
4
5
n-C4H9
n-C4H9
n-C5H11
n-C5H11
n-C6H13
Me (R-4h)
Me (S-4h)
Me (R-4j)
Me (S-4j)
Me (R-4a)
499
96
499
499
499
p-BnO2CC6H4
p-BnO2CC6H4
p-NCC6H4
p-NCC6H4
p-Me(O)CC6H4
77 (R-5p)
77 (S-5p)
82 (R-5r)
83 (S-5r)
71 (R-5c)
99
95
98
96
97
a
b
Isolated yield. The ee value was determined by HPLC.
from 71 to 83%. Racemization of the chiral centers in
(R)- or (S)-4 is not clearly evident.
(b) Modern Allene Chemistry, ed. N. Krause and A. S. K. Hashmi,
Wiley-VCH, Weinheim, 2004, vol. 2; (c) S. Ma, in Topics in
Organometallic Chemistry, ed. J. Tsuji, Springer, Berlin Germany,
2005, p. 183; (d) R. Zimmer, C. U. Dinesh, E. Nandanan and
F. A. Khan, Chem. Rev., 2000, 100, 3067; (e) R. W. Bates and
V. Satcharoen, Chem. Soc. Rev., 2002, 31, 12; (f) Y. Yamamoto
and U. Radhakrishnan, Chem. Soc. Rev., 1999, 28, 199.
In conclusion, we have developed a mild and efficient
method for the regioselective synthesis of 2,3-dihydro-1H-
pyrazoles. By using the readily available enantiomerically
enriched 2,3-allenyl hydrazines, optically active 2,3-dihydro-
1H-pyrazoles with high ee values can be synthesized
conveniently. The reaction may proceed via oxidative addition
followed by carbopalladation forming a p-allylic palladium
intermediate or by a nucleometalation–reductive elimination
pathway.5c Further studies in this area are being conducted in
our laboratory.
6 For some of the most recent typical reactions of allenes, see:
(a) J. D. Sieber and J. P. Morken, J. Am. Chem. Soc., 2006, 128,
74; (b) P. H. Lee, K. Lee and Y. Kang, J. Am. Chem. Soc., 2006,
128, 1139; (c) S. Ma and Z. Gu, J. Am. Chem. Soc., 2006, 128,
4942; (d) B. M. Trost and J. Xie, J. Am. Chem. Soc., 2006, 128,
6044; (e) Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian and
R. A. Widenhoefer, J. Am. Chem. Soc., 2006, 128, 9066;
(f) J. E. Wilson and G. C. Fu, Angew. Chem., Int. Ed., 2006, 45,
1426; (g) N. Morita and N. Krause, Angew. Chem., Int. Ed., 2006,
45, 1897; (h) N. Nishina and Y. Yamamoto, Angew. Chem., Int.
Ed., 2006, 45, 3314; (i) H. Guo, Z. Zheng, F. Yu, S. Ma,
A. Holuigue, D. S. Tromp, C. J. Elsevier and Y. Yu, Angew.
Chem., Int. Ed., 2006, 45, 4997; (j) P. L. Lalonde, B. D. Sherry,
E. J. Kang and F. D. Toste, J. Am. Chem. Soc., 2007, 129, 2452;
(k) H.-T. Chang, T. T. Jayanth and C.-H. Cheng, J. Am. Chem.
Soc., 2007, 129, 4166; (l) C. S. Lopez, O. N. Faza, K. S. Feldman,
M. R. Iyer and D. K. Hester II, J. Am. Chem. Soc., 2007, 129,
7638; (m) Z. Gu, X. Wang, W. Shu and S. Ma, J. Am. Chem. Soc.,
2007, 129, 10948.
7 (a) S. Ma and Z. Shi, J. Org. Chem., 1998, 63, 6387; (b) S. Ma,
D. Duan and Z. Shi, Org. Lett., 2000, 2, 1419; (c) S. Ma and
H. Xie, Org. Lett., 2000, 2, 3801; (d) S. Ma and H. Xie, J. Org.
Chem., 2002, 67, 6575; (e) S. Ma and S. Zhao, J. Am. Chem. Soc.,
1999, 121, 7943; (f) S. Ma and W. Gao, Tetrahedron Lett., 2000, 41,
8933; (g) S. Ma and W. Gao, J. Org. Chem., 2002, 67, 6104;
(h) S. Ma and J. Zhang, Chem. Commun., 2000, 117; (i) S. Ma and
L. Li, Org. Lett., 2000, 2, 941; (j) S. Ma and S. Zhao, Org. Lett.,
2000, 2, 2495; (k) S. Ma, N. Jiao, S. Zhao and H. Hou, J. Org.
Chem., 2002, 67, 2837; (l) S. Ma, N. Jiao, Q. Yang and Z. Zheng,
J. Org. Chem., 2004, 69, 6463; (m) S. Ma and W. Gao, Org. Lett.,
2002, 4, 2989; (n) S. Ma, F. Yu, J. Li and W. Gao, Chem.–Eur. J.,
2007, 13, 247.
Financial supports from the Major State Basic Research
Development Program (Grant No. 2006CB806105), National
Natural Science Foundation of China (No. 20732005 and
20423001), and Shanghai Municipal Committee of Science
and Technology are greatly appreciated.
Notes and references
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Z. Urbanczyk-Lipkowska, K. Suwinska, J. Solecka and
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A. S. Al-Kamali, Can. J. Chem., 2002, 80, 1293; (g) R. Shintani and
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P. Cuadrado and A. Gonzalez-Ortega, Eur. J. Org. Chem., 2005,
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8 X. Cheng and S. Ma, Angew. Chem., Int. Ed., 2008, 47, 4581.
9 (a) O. Mitsunobu, Synthesis, 1981, 1; (b) O. Mitsunobu,
M. Yamada and T. Mukaiyama, Bull. Chem. Soc. Jpn., 1967, 40,
935.
10 Crystal data for compound 5v: C33H33N3O6, M = 567.62, mono-
clinic, space group P21/c, a = 14.1841(4), b = 25.4026(7), c =
8.5968(2) A, b = 107.6040(10)1, V = 2952.48(14) A3, T = 296(2)
K, Z = 4, reflections collected/unique (Mo-Ka radiation): 34090/
5209 (Rint = 0.0295), number of observations [4 2s(I)] 4031,
parameters 379. Final R indices [I 4 2s(I)]: R1 = 0.0412, wR2 =
0.1059; R indices (all data): R1 = 0.0566, wR2 = 0.1199.
11 (a) D. Xu, Z. Li and S. Ma, Chem.–Eur. J., 2002, 21, 5012;
(b) D. Xu, Z. Li and S. Ma, Tetrahedron: Asymmetry, 2003, 14,
3657; (c) D. Xu, Z. Li and S. Ma, Tetrahedron Lett., 2003, 44, 6343;
(d) D. Xu, Z. Lu, Z. Li and S. Ma, Tetrahedron, 2004, 60, 11879.
4 V. Nair, S. C. Mathew, A. T. Biju and E. Suresh, Angew. Chem.,
Int. Ed., 2007, 46, 2070.
5 (a) For recent reviews on Pd-catalyzed cyclization of allenes with
organic halides, see: S. Ma, Acc. Chem. Res., 2003, 36, 701;
ꢀc
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