S.V. Pansare, R.L. Kirby / Tetrahedron 65 (2009) 4557–4561
4561
3.80 mmol) and the solution was stirred at room temperature un-
Supplementary data
der N2 for 48 h. The reaction mixture was cooled to 0 ꢁC, treated
with 6 N HCl (2 mL), and stirred for 3 h after which time the
resulting mixture was concentrated under reduced pressure. The
residue obtained was dissolved in H2O (5 mL) and the solution was
washed with EtOAc (2ꢂ5 mL). The aqueous layer was basified with
6 N NaOH and extracted with EtOAc (3ꢂ10 mL). The combined or-
ganic layers were dried (Na2SO4), filtered, and concentrated. The
crude product was purified using flash chromatography on silica gel
(95/5 CH2Cl2/CH3OH to 90/10 CH2Cl2/CH3OH) to provide 95 mg
(63%) of diamine 5 as a yellow solid.
Experimental details and data for compounds 8–17.
Supplementary data associated with this article can be found in
References and notes
1. Recent reviews: (a) Almasi, D.; Alonso, D. A.; Najera, C. Tetrahedron: Asymmetry
2007, 18, 299; (b) Tsogoeva, S. Eur. J. Org. Chem. 2007, 1701; (c) Vicario, J. L.;
Badia, D.; Carrillo, L. Synthesis 2007, 2065.
1H NMR (500 MHz, CDCl3):
d
8.11 (d, 2H, J¼9.35, ArH, ortho to
2. Reviews: (a) Kotsuki, H.; Ikishima, H.; Okuyama, A. Heterocycles 2008, 75,
757; (b) Sulzer-Mosse, S.; Alexakis, A. Chem. Commun. 2007, 3123; (c) Enders,
D.; Seki, A. Eur. J. Org. Chem. 2002, 1877; Some recent reports: (d) Ni, B.;
Zhang, Q.; Dhungana, K.; Headley, A. D. Org. Lett. 2009, 11, 1041; (e)
Okuyama, Y.; Nakano, H.; Watanabe, Y.; Makabe, M.; Takeshita, M.; Uwai, K.;
Kabuto, C.; Kwan, E. Tetrahedron Lett. 2009, 50, 193; (f) Li, J.; Hu, S.; Luo, S.;
Cheng, J.-P. Eur. J. Org. Chem. 2009, 132; (g) Karthikeyan, T.; Sankararaman, S.
Tetrahedron: Asymmetry 2008, 19, 2741; (h) Xue, F.; Zhang, S.; Duan, W.;
Wang, W. Adv. Synth. Catal. 2008, 350, 2194; (i) Yang, Z.; Liu, J.; Liu, X.;
Wang, Z.; Feng, X.; Su, Z.; Hua, C. Adv. Synth. Catal. 2008, 350, 2001; (j) Xu,
D.-Q.; Yue, H.-D.; Luo, S.-P.; Xia, A.-B.; Zhang, S.; Xu, Z.-Y. Org. Biomol. Chem.
2008, 6, 2054; (k) Xu, D.-Q.; Wang, L.-P.; Luo, S.-P.; Wang, Y.-F.; Zhang, S.;
Xu, Z.-Y. Eur. J. Org. Chem. 2008, 6, 1049; (l) Luo, S.; Zhang, L.; Mi, X.; Qiao,
Y.; Cheng, J.-P. J. Org. Chem. 2007, 72, 9350; (m) Liu, F.; Wang, S.; Wang, N.;
Peng, Y. Synlett 2007, 2415; (n) Wu, L.-Y.; Yan, Z.-Y.; Xie,
Y.-X.; Niu, Y.-N.; Liang, Y.-M. Tetrahedron: Asymmetry 2007, 18, 2086; (o)
Xiong, Y.; Wen, Y.; Wang, F.; Gao, B.; Liu, X.; Huang, X.; Feng, X. Adv. Synth.
Catal. 2007, 349, 2156; (p) Mandal, T.; Zhao, C.-G. Tetrahedron Lett. 2007, 48,
5803; (q) Xu, D.-Q.; Wang, B.-T.; Luo, S.-P.; Yue, H.-D.; Wang, L.-P.; Xu, Z.-Y.
Tetrahedron: Asymmetry 2007, 18, 1788; (r) Gu, L.-Q.; Zhao, G. Adv. Synth.
Catal. 2007, 349, 1629; (s) Almasi, D.; Alonso, D. A.; Go´ mez-Bengoa, E.; Nagel,
NO2), 6.57 (d, 2H, J¼9.35, ArH), 3.96 (m, 1H, CHCH2), 3.47 (m, 1H,
CH2N), 3.27 (m, 1H, CH2N), 2.75 (dd, 1H, J¼3.58, 12.06, CH2NCH3),
2.55 (dd, 1H, J¼8.65, 12.06, CH2NCH3), 2.48 (s, 3H, NCH3), 2.12–2.01
(m, 4H, CH2CH2). 13C NMR (125.8 MHz, CDCl3):
d 152 (ArCNO2),
137.4 (ArCN), 126.7 (ArC, ortho to NO2), 111.3 (ArC), 59.1 (CHN), 53.5
(CH2N), 49 (CH2N), 37.1 (NCH3), 29.8 (CH2), 23.5 (CH2). IR (neat):
1594, 1478, 1288, 1195, 1108, 822 cmꢀ1. MS: m/z 236.1 (Mþ1, 100).
HRMS: m/z 235.1324 (235.1321 calcd for C12H17N3O2 (Mþ)).
4.5. General experimental procedure for the Michael addition
of ketones to nitroalkenes
Toa solution of the amine catalyst(0.1 mmol) and thenitroalkene
(0.5 mmol) in toluene (1 mL) was added the ketone (2.5 mmol), and
the solution was stirred at ambient temperature for 48–72 h except
when noted otherwise. Ethyl acetate (10 vol) was added and the
solution was washed with water, aqueous 0.5 N HCl, dried (Na2SO4),
filtered, and concentrated to give the crude product, which was
purified by flash chromatography on silica gel.
The relative configurations of the products (syn or anti) were
determined by comparison of 1H NMR spectral data with those
reported in the literature. The absolute configurations of each
product were determined either by comparison of optical rotation
values with those reported in the literature or by comparison of
HPLC retention times. Spectral data for compounds 8–17 are in
agreement with literature reports.
´
Y.; Najera, C. Eur. J. Org. Chem. 2007, 2328; (t) Shen, Z.; Zhang, Y.; Jiao, C.; Li,
B.; Ding, J.; Zhang, Y. Chirality 2007, 19, 307; (u) Liu, K.; Cui, H.-F.; Nie, J.;
Dong, K.-Y.; Li, X.-J.; Ma, J.-A. Org. Lett. 2007, 9, 923; (v) Cao, Y.-J.; Lai, Y.-Y.;
Wang, X.; Li, Y.-J.; Xiao, W.-J. Tetrahedron Lett. 2007, 48, 21; (w) Yan, Z.-Y.;
Niu, Y.-N.; Wei, H.-L.; Wu, L.-Y.; Zhao, Y.-B.; Liang, Y.-M. Tetrahedron: Asym-
metry 2006, 17, 3288.
3. Recent review: (a) Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev.
2007, 107, 5471.
4. Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37, 570 and references
therein.
5. (a) Alexakis, A.; Andrey, O. Org. Lett. 2002, 4, 3611; (b) For a recent report on
aminal-based organocatalysts, see: Quintard, A.; Bournaud, C.; Alexakis, A.
Chem.dEur. J. 2008, 14, 7504.
6. For a study of the effect of N-substitution on the pKa of secondary amines, see:
Fraser, R. R.; Mansour, T. S. J. Org. Chem. 1984, 49, 3443.
7. (a) Enders, D.; Seki, A. Synlett 2002, 26; (b) Hoashi, Y.; Okino, T.; Takemoto, Y.
Angew. Chem., Int. Ed. 2005, 44, 4032; (c) Huang, H.; Jacobsen, E. N. J. Am. Chem.
Soc. 2006, 128, 7170; (d) Cobb, A. J. A.; Shaw, D. M.; Longbottom, D. A.; Gold,
J. B.; Ley, S. V. Org. Biomol. Chem. 2005, 3, 84; (e) Lattanzi, A. Tetrahedron:
Asymmetry 2006, 17, 837; For reviews on hydrogen bonding in the context of
organocatalysis, see: (f) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006,
45, 1520; (g) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713; (h) Yu, X.;
Wang, W. Chem. Asian J. 2008, 3, 516.
8. (a) Bahmanyar, S.; Houk, K. J. Am. Chem. Soc. 2001, 123, 12911; (b) Wang, J.; Li,
H.; Lou, B.; Zu, L.; Guo, H.; Wang, W. Chem.dEur. J. 2006, 12, 4321.
9. Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672.
10. Mitchell, C. E. T.; Cobb, A. J. A.; Ley, S. V. Synlett 2005, 611.
11. The pKa values were calculated using the SPARC software: Hilal, S.; Karickhoff,
4.5.1. (S)-2-[(R)-2-Nitro-1-phenylethyl]-4-[1,3-dioxolanyl]-
cyclohexanone (13)8b,14a
Reaction of 4-(1,3-dioxolanyl)-cyclohexanone (395 mg, 2.5 mmol)
and 1-((E)-2-nitrovinyl)benzene (74.5 mg, 0.5 mmol) in the presence
of catalyst 1 (16.7 mg, 0.1 mmol) according to the general procedure
gave, after purification by flash chromatography on silica gel (ethyl
acetate/hexane: 40/60), 121 mg (79%) of 13 as a white solid.
1H NMR (500 MHz, CDCl3):
d 7.35–7.28 (m, 3H, ArH), 7.21 (d, 2H,
J¼7.50, ortho ArH), 4.95 (dd, 1H, J¼12.50, 4.71, CH2NO2), 4.63 (dd,
1H, J¼12.50, 9.82, CH2NO2), 4.04–3.81 (m, 5H, PhCH, OCH2CH2O),
3.10–3.05 (m, 1H, CHC(O)), 2.71 (dt, 1H, J¼6.41, 13.43, CH2CH2), 2.42
(ddd, 1H, J¼13.81, 3.59, 1.52, CH2CH2), 2.04–2.01 (m, 1H, CH2CH2),
2.00–1.91 (m, 1H, CH2CH2), 1.72–1.66 (ddd, 1H, J¼13.37, 3.52, 1.87,
CH2CH), 1.60–1.52 (m, 1H, CH2CH).
12. Pansare, S. V.; Pandya, K. J. Am. Chem. Soc. 2006, 128, 9624.
13. Edwards, C. W.; Shipton, M. R.; Alcock, N. W.; Clase, H.; Wills, M. Tetrahedron
2003, 59, 6473.
14. For representative examples, see: (a) Vishnumaya; Singh, V. K. Org. Lett.
2007, 9, 1117; (b) Mase, N.; Watanabe, K.; Yoda, H.; Takabe, K.; Tanaka, F.;
Barbas, C. F. J. Am. Chem. Soc. 2006, 128, 4966; (c) Zhu, M.-K.; Cun, L.-F.;
Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. Tetrahedron: Asymmetry 2006, 17, 491; (d)
Betancort, J. M.; Barbas, C. F. Org. Lett. 2001, 3, 3737; (e) Betancort, J. M.;
Sakthivel, K.; Thayumanavan, R.; Barbas, C. F. Tetrahedron Lett. 2001, 42,
4441; (f) Betancort, J. M.; Sakthivel, K.; Thayumanavan, R.; Tanaka, F.;
Barbas, C. F. Synthesis 2004, 1509; (g) Mase, N.; Thayumanavan, R.; Tanaka,
F.; Barbas, C. F. Org. Lett. 2004, 6, 2527; (h) Andrey, O.; Alexakis, A.;
Tomassani, A.; Bernardinelli, G. Adv. Synth. Catal. 2004, 346, 1147; (i) Luo,
S.; Xu, H.; Li, J.; Zhang, L.; Mi, X.; Zheng, X.; Cheng, J.-P. Tetrahedron 2007,
63, 11307; (j) Luo, S.; Li, J.; Zhang, L.; Xu, H.; Cheng, J.-P. Chem.dEur. J.
2008, 14, 1273; (k) Chen, H.; Wang, Y.; Wei, S.; Sun, J. Tetrahedron:
Asymmetry 2007, 18, 1308.
HPLC (Chiralpak AS-H): (hexane/i-PrOH, 90/10, flow rate
0.5 mL minꢀ1
92%
,
l
¼254 nm): tmajor¼59.6 min, tminor¼47.5 min, ee:
Acknowledgements
Financial support from the Natural Sciences and Engineering
ResearchCouncilofCanada andtheCanadaFoundationforInnovation
is gratefully acknowledged. We thank Mr. Timothy Morgan for tech-
nical assistance.