The Journal of Organic Chemistry
NOTE
results support the generation of a Schiff base in the initial step of
the condensation reaction. Finally, it was confirmed that the
addition of 2a to the reaction mixture of 4b and 1a provides
nitrostyrene 3a (Figure 1d).
Spectroscopic data of 7aÀb,3 7cÀe,5l,ad 7f,3 7g,5l,ad and 7hÀk3 are in
agreement with the published data.,
’ ASSOCIATED CONTENT
A plausible reaction mechanism of the condensation reaction
of 1a with 2a by catalyst 4b is depicted in Scheme 3. Initially, a
Schiff base 8, which can form an oxazolidinone 9, is generated
from 1a and 4b.10 Then the oxazolidinone 9, which is a stronger
base than the Schiff base 8, removes a proton from 2a to give a
nitronate, which attacks 1a or 8 to produce β-nitroalcohol 5 or
β-nitroamine 10. Finally, the oxazolidinone 9 promotes dehy-
dration or dehydroamination of 5 or 10 to provide nitroalkene
3a.11 The lithium cation of the catalyst will assist the dehydration
or dehydroamination by its Lewis acidity12 since the condensa-
toin reaction in DMSO, which can cause strong solvation of a
lithium cation, gave only a β-nitroalcohol as shown in Scheme 2.
In conclusion, we found that a primary amino acid lithium salt,
O-tert-butyldiphenylsilyl L-tyrosine lithium salt, is an effective
catalyst for one-pot asymmetric synthesis of γ-nitroaldehydes
from aldehydes and nitroalkanes. The catalyst played two
different roles in the reaction: (1) a role as a catalyst for
generation of a nitroalkene directly from an aldehyde and a
nitroalkane and (2) a role as an organocatalyst for asymmetric
Michael addition of an aldehyde to a nitroalkene to provide a
γ-nitroaldehyde. By using the present method, various aryl,
alkenyl, and alkyl aldehydes were converted into γ-nitroalde-
hydes in good yields with high enantioselectivity without isola-
tion of nitroalkenes. The present method will also be useful for
stereoselective synthesis of nitroalkenes under mild reaction
conditions.
S
SupportingInformation. ExperimentaldetailsofScheme2
b
and Figure 1, 1H NMR spectra of 3e, 3i, 3l,m, 3o, and 7aÀk, and
HPLC analysis of 7aÀk. This material is available free of charge via
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: myoshida@eng.hokudai.ac.jp.
’ ACKNOWLEDGMENT
This work was partly supported by the Global COE Program
(Project No. B01: Catalysis as the Basis for Innovation in
Materials Science) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
’ REFERENCES
(1) The number of reports related to “green chemistry” or “one-pot
and tandem” was analyzed by SciFinder Scholar.
(2) Scroggins, S. T.; Chi, Y.; Frꢀechet, J. M. J. Angew. Chem., Int. Ed.
2010, 49, 2393.
(3) (a) Yoshida, M.; Sato, A.; Hara, S. Org. Biomol. Chem. 2010,
8, 3031. (b) Sato, A.; Yoshida, M.; Hara, S. Chem. Commun. 2008, 6242.
(4) Reviews on asymmetric Michael addition of aldehydes to
nitroalkenes: (a) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org.
Chem. 2002, 1877. (b) Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 1701. (c)
Alma-si, D.; Alonso, D. A.; Nꢀajera, C. Tetrahedron: Asymmetry 2007,
18, 299.
’ EXPERIMENTAL SECTION
(5) Asymmetric Michael addition of aldehydes to nitroalkenes with a
secondary amine catalyst: (a) Zhu, S.; Yu, S.; Wang, Y.; Ma, D. Angew.
Chem., Int. Ed. 2010, 49, 4656. (b) Enders, D.; Kruell, R.; Bettray, W.
Synthesis 2010, 567. (c) Kelleher, F.; Kelly, S.; Watts, J.; McKee, V.
Tetrahedron 2010, 66, 3525. (d) Hu, F.; Guo, C.-S.; Xie, J.; Zhu, H.-L.;
Huang, Z.-Z. Chem. Lett. 2010, 39, 412. (e) Bai, J.-F.; Xu, X.-Y.; Huang,
Q.-C.; Peng, L.; Wang, L.-X. Tetrahedron Lett. 2010, 51, 2803. (f) Lu, D.;
Gong, Y.; Wang, W. Adv. Synth. Catal. 2010, 352, 644. (g) Wang, B. G.;
Ma, B. C.; Wang, Q.; Wang, W. Adv. Synth. Catal. 2010, 352, 2923. (h)
Demir, A. S.; Eymur, S. Tetrahedron: Asymmetry 2010, 21, 112. (i)
Wiesner, M.; Neuburger, M.; Wennemers, H. Chem.ÀEur. J. 2009,
15, 10103. (j) Lombardo, M.; Chiarucci, M.; Quintavalla, A.; Trombini,
C. Adv. Synth. Catal. 2009, 351, 2801. (k) Luo, R.-S.; Weng, J.; Ai, H.-B.;
Lu, G.; Chan, A. S. C. Adv. Synth. Catal. 2009, 351, 2449. (l) Chang, C.;
Li, S.-H.; Reddy, R. J.; Chen, K. Adv. Synth. Catal. 2009, 351, 1273. (m)
Laars, M.; Ausmees, K.; Uudsemaa, M.; Tamm, T.; Kanger, T.; Lopp, M.
J. Org. Chem. 2009, 74, 3772. (n) Zhang, X.-J.; Liu, S.-P.; Li, X.-M.; Yan,
M.; Chan, A. S. C. Chem. Commun. 2009, 833. (o) Guo, L.; Chi, Y.;
Almeida, A. M.; Guzei, I. A.; Parker, B. K.; Gellman, S. H. J. Am. Chem.
Soc. 2009, 131, 16018. (p) Wiesner, M.; Revell, J. D.; Tonazzi, S.;
Wennemers, H. J. Am. Chem. Soc. 2008, 130, 5610. (q) Chi, Y.; Guo, L.;
Kopf, N. A.; Gellman, S. H. J. Am. Chem. Soc. 2008, 130, 5608. (r)
Wiesner, M.; Revell, J. D.; Wennemers, H. Angew. Chem., Int. Ed. 2008,
47, 1871. (s) García-García, P.; Ladꢀep^eche, A.; Halder, R.; List, B. Angew.
Chem. Int., Ed. 2008, 47, 4719. (t) Hayashi, Y.; Ito, T.; Ohkubo, M.;
Ishikawa, H. Angew. Chem., Int. Ed. 2008, 47, 4722. (u) Wu, L.-Y.; Yan,
Z.-Y.; Xie, Y.-X.; Niu, Y.-N.; Liang, Y.-M. Tetrahedron: Asymmetry 2007,
18, 2086. (v) Barros, M. T.; Phillips, A. M. F. Eur. J. Org. Chem.
2007, 178. (w) Mase, N.; Watanabe, K.; Yoda, H.; Takabe, K.; Tanaka,
F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 4966. (x) Palomo, C.;
Vera, S.; Mielgo, A.; Gꢀomez-Bengoa, E. Angew. Chem., Int. Ed. 2006,
45, 4984. (y) Wang, J.; Li, H.; Lou, B.; Zu, L.; Guo, H.; Wang, W. Chem.
Typical Procedure for the Synthesis of Nitroalkenes 3. In a
7 mL vial, p-anisaldehyde (1b) (68 mg, 0.5 mmol) and nitromethane (2a)
(153 mg, 2.5 mmol) were successively added to a slurry of O-tert-
butyldiphenylsilyl L-tyrosine lithium salt (4b) (42.5 mg, 0.1 mmol), MgSO4
(60 mg, 0.5 mmol), and CH2Cl2 (1 mL) at 25 °C. After 24 h of stirring at
25 °C, sat. aq. NaCl (1.5 mL) was added to the vial and extracted with Et2O
(3 Â 2 mL). The combined organic phase was dried over MgSO4, filtered,
and concentrated under reduced pressure. (E)-1-(4-Methoxyphenyl)-2-
nitroethene (3b) was isolated by column chromatography (silica gel,
hexane/Et2O) in 85% yield (76 mg) as a yellow solid. δH (CDCl3) 3.88
(3H, s), 6.96 (2H, d, J = 8.8 Hz), 7.50À7.55 (3H, m), 7.99 (1H, d,
J = 13.6 Hz).
Spectroscopic data of 3aÀd, 3fÀh, 3j, and 3k are in agreement with
that of samples purchased from commercial suppliers. Spectroscopic
data of 3e,13a 3i,13b 3l,13c 3m,13d and 3o13e are in agreement with the
published data.
Typical Procedure for the One-Pot Asymmetric Synthesis
of γ-Nitroaldehydes 7. In a 7 mL vial, benzaldehyde (1a) (53 mg,
0.5 mmol) and 2a (153 mg, 2.5 mmol) were successively added to a
slurry of 4b (42.5 mg, 0.1 mmol), MgSO4 (60 mg, 0.5 mmol), and
CH2Cl2 (1 mL) at 25 °C. After 48 h of stirring at 25 °C, isobutyr-
aldehyde (72 mg, 1 mmol) was added to the resulting reaction mixture.
After a further 72 h of stirring, the same workup was performed as
mentioned above. (S)-2,2-Dimethyl-4-nitro-3-phenylbutanal (7a)3 was
isolated by column chromatography (silica gel, hexane/Et2O) in 81%
yield (89.5 mg) as a yellow oil. The enantioselectivity was determined by
HPLC analysis (96% ee). δH (CDCl3) 1.01 (3H, s), 1.14 (3H, s), 3.79
(1H, dd, J = 4.2, 11.3 Hz), 4.69 (1H, dd, J = 4.2, 13.1 Hz), 4.86 (1H, dd,
J = 11.3, 13.1 Hz), 7.20À7.21 (2H, m), 7.30À7.36 (3H, m), 9.53 (1H, s).
2308
dx.doi.org/10.1021/jo102570p |J. Org. Chem. 2011, 76, 2305–2309