Representative asymmetric version of the three-component
procedure
11 A. Baeza, C. Na´jera and J. M. Sansano, Synthesis, 2007, 1230.
12 Selected reviews: (a) B. List, Tetrahedron, 2002, 58, 5573; (b) P. I.
Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138; (c) W.
Notz, F. Tanaka and C. F. Barbas III, Acc. Chem. Res., 2004, 37,
580; (d) P. I. Dalko, Enantioselective Organocatalysis, Wiley-VCH,
Weinheim, Germany, 2007.
2-(4-methoxyphenylamino)-2-phenylpropanenitrile (2a). Brøn-
sted acid catalyst (17.5 mg, 0.025 mmol) was added to a mixture of
acetophenone (31.5 mg, 0.262 mmol), 4-methoxylaniline (30.8 mg,
13 For a review, see: (a) P. Merino, E. Marque´s-Lo´pez, T. Tejero and
R. P. Herrera, Tetrahedron, 2009, 65, 1219. Selected recent examples:
(b) M. J. Sigman, P. Vachal and E. N. Jacobsen, Angew. Chem., Int.
Ed., 2000, 39, 1279; (c) P. Vachal and E. N. Jacobsen, Org. Lett., 2000,
2, 867; (d) D. Seebach, A. K. Beck and A. Heckel, Angew. Chem., Int.
Ed., 2001, 40, 92; (e) B. Liu, X. Feng, F. Chen, G. Zhang, X. Cui and
Y. Jiang, Synlett, 2001, 1551; (f) P. Vachal and E. N. Jacobsen, J. Am.
Chem. Soc., 2002, 124, 10012; (g) A. G. Wenzel, M. P. Lalonde and E. N.
Jacobsen, Synlett, 2003, 1919; (h) Z. Jiao, X. Feng, B. Liu, F. Chen,
G. Zhang and Y. Jiang, Eur. J. Org. Chem., 2003, 3818; (i) J. Huang
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Sgarzani, L. Bernardi, F. Fini, D. Pettersen and A. Ricci, J. Org. Chem.,
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Soc., 2006, 128, 2548; (p) M. Rueping, E. Sugiono and C. Azap, Angew.
Chem., Int. Ed., 2006, 45, 2617; (q) S. C. Pan and B. List, Synlett, 2007,
318; (r) S. C. Pan and B. List, Org. Lett., 2007, 9, 1149; (s) Y. Wen, Y.
Xiong, L. Chang, J. Huang, X. Liu and X. Feng, J. Org. Chem., 2007,
72, 7715; (t) J. Huang, X. Liu, Y. Wen, B. Qiu and X. Feng, J. Org.
Chem., 2007, 72, 204; (u) M. Negru, D. Schollmeyer and H. Kunz,
Angew. Chem., Int. Ed., 2007, 46, 9339; (v) I. V. P. Raj, G. Suryavanshi
and A. Sudalai, Tetrahedron Lett., 2007, 48, 7211; (w) J. Wang, X. L.
Hu, J. Jiang, S. H. Gou, X. Huang, X. H. Liu and X. M. Feng, Angew.
Chem., Int. Ed., 2007, 46, 8468.
˚
0.25 mmol), TMSCN (37.2 mg, 0.375 mmol) and powdered 4 A
molecular sieves (50 mg) in toluene (0.5 mL). The resulting mixture
was stirred at 40 ◦C for 48 h. Then, the reaction solution was
concentrated under vacuum, and the residue was purified by silica
gel flash column chromatography (petroleum ether–AcOEt: 20 : 1)
to give the desired product as a white solid: 45.9 mg (73% yield,
40% ee).
73% yield, 40% ee [Daicel Chiralcel AD-H, hexanes–iPrOH =
80 : 20, 0.5 mL min-1, l = 254 nm, tR (minor) = 14.163 min, tR
(major) = 17.404 min].
2-phenyl-2-(phenylamino)propanenitrile (2b). 81% yield, 21%
ee [Daicel Chiralcel AD-H, hexanes–iPrOH
=
80 : 20,
0.5 mL min-1, l = 254 nm, tR (minor) = 12.120 min, tR (major) =
12.995 min].
2-(4-methoxyphenylamino)-2-(4-fluorophenyl)propanenitrile (2g).
78% yield, 20% ee [Daicel Chiralcel AD-H, hexanes–iPrOH =
80 : 20, 0.5 mL min-1, l = 254 nm, tR (minor) = 12.395 min, tR
(major) = 14.936 min].
14 (a) T. Akiyama, J. Itoh, K. Yokota and K. Fuchibe, Angew. Chem.,
Int. Ed., 2004, 43, 1566; (b) D. Uraguchi and M. Terada, J. Am.
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Terada, Chem. Commun., 2008, 4097; (f) G. Adair, S. Mukherjee and
B. List, Aldrichimica Acta, 2008, 41, 31. For some selected examples
of phosphoricacid catalyzed multicomponent reactions, see: (g) R. I.
Storer, D. E. Carrera, Y. Ni and D. W. C. MacMillan, J. Am. Chem.
Soc., 2006, 128, 84; (h) X.-H. Chen, X.-Y. Xu, H. Liu, L.-F. Cun and
L.-Z. Gong, J. Am. Chem. Soc., 2006, 128, 14802; (i) Q.-X. Guo, H.
Liu, C. Guo, S.-W. Luo, Y. Gu and L.-Z. Gong, J. Am. Chem. Soc.,
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Acknowledgements
This work was supported financially by the National Natural Sci-
ence Foundation of China (No. 20772091) and Tianjin Municipal
Science & Technology Commission (No. 07JCDJC04700).
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