.
Angewandte
Communications
Gçergens, WO2012004326, 2012; k) T. Mita, M. Iwasa, H.
Imanaka, JP2012031148, 2012; l) K. Kçerber, F. Kaiser, W.
Von Deyn, P. Deshmukh, A. Narine, J. Dickhaut, N. G. Bandur,
D. L. Culbertson, D. D. Anspaugh, F.-J. Braun, WO2012042007,
2012; m) J. Y. Cassayre, M. El Qacemi, T. Luksch, P. Renold,
WO2012156400, 2012; n) J. Y. Cassayre, P. Renold, M. El Qa-
cemi, T. Pitterna, J. C. Toueg, WO 2012163959, 2012.
Figure 3. Agrochemicaly important trifluoromethylated pyrrolines 7.
[5] More than 7000 compounds 3 had been registered in the
SciFinder data base by February, 2013.
[6] a) T. Murata, H. Kishikawa, H. Watanabe, E. Shimojo, T.
Ichihara, M. Ataka, K. Shibuya, T. Ishikawa, U. Goergens,
WO2012034957, 2012; b) T. Murata, H. Kishikawa, H. Wata-
nabe, E. Shimojo, T. Ichihara, M. Ataka, K. Shibuya, T.
Ishikawa, U. Goergens, JP2012062267, 2012.
In summary, we have developed an operationally simple,
highly enantioselective conjugate addition of nitromethane to
the sterically demanding b-aryl-b-trifluoromethyl-substituted
enones 2 catalyzed by the novel cupreidine-based phase-
transfer catalyst 4g to provide conjugate addition adducts
having trifluoromethylated all-carbon quaternary stereocen-
ters. Ether-type, 9-OH-protected cupreidinium salts are
crucial for this transformation, which gives excellent chemical
yields and enantioselectivities (over 90% ee). Transformation
to the biologically important trifluoromethylated arylpyrro-
lines 3 and their N-oxide 6 were achieved from the nitro-
methane adduct 5 with high to excellent yields by a single
step. The optically active N-oxides 6 are attractive as polar
isosteres of 3 and the biological evaluation of chiral 6 is under
investigation.
[7] For selected examples using organocatalysts, see: a) A. P. Davis,
8331 – 8338; d) M. T. Allingham, A. Howard-Jones, P. J. Murphy,
J. Ye, P. Li, Y. Wang, Chem. Commun. 2008, 3302 – 3304; i) K.
Mei, M. Jin, S. Zhang, P. Li, W. Liu, X. Chen, F. Xue, W. Duan,
phase-transfer catalysts, see: k) S. Colonna, H. Hiemstra, H.
For selected examples using metal complexes, see: q) E. Keller,
s) M. S. Taylor, D. N. Zalatan, A. M. Lerchner, E. N. Jacobsen, J.
Received: February 7, 2013
Revised: April 10, 2013
Published online: April 18, 2013
Keywords: enantioselectivity · fluorine · heterocycles ·
.
organocatalysis · synthetic methods
c) Hydrogen Bonding in Organic Synthesis (Ed.: P. M. Pihko),
Wiley-VCH, Weinheim, 2009.
[2] K. Matoba, H. Kawai, T. Furukawa, A. Kusuda, E. Tokunaga, S.
[8] a) C. E. T. Mitchell, S. E. Brenner, S. V. Ley, Chem. Commun.
[3] H. Kawai, S. Okusu, E. Tokunaga, H. Sato, M. Shiro, N. Shibata,
´
[4] For example, see: a) T. Mita, Y. Kudo, T. Mizukoshi, H. Hotta, K.
Maeda, S. Takii, JP2005272452, 2005; b) T. Mita, E. Ikeda, H.
Takahashi, M. Komoda, WO2009072621, 2009; c) U. Gçergens,
Y. Yoneta, T. Murata, J. Mihara, K. Domon, E. Shimojo, K.
Shibuya, T. Ichihara, WO2009097992, 2009; d) J. Y. Cassayre, P.
Renold, T. Pitterna, V. Bobosik, M. El Qacemi, A. J. Dalencon,
W. Zambach, C. R. Godfrey, P. J. Jung, J. Pabba, WO2010020522,
2010; e) H. Ihara, K. Kumamoto, WO2010090344, 2010; f) T.
Murata, Y. Yoneta, H. Kishikawa, J. Mihara, D. Yamazaki, M.
Hatazawa, N. Sasaki, K. Domon, E. Shimojo, T. Ichihara, K.
Shibuya, M. Ataka, U. Gçergens, WO2010133336, 2010;
g) A. W. Moradi, T. N. Mueller, T. Murata, M. Hatazawa, P.
Bruechner, E. Shimojo, T. Ichihara, M. Ataka, K. Shibuya, U.
Gçergens, WO2011128299, 2011; h) K. Araki, J. Mihara, N.
Sasaki, P. Bruechner, K. Domon, J.-R. Jansen, N. Lui,
WO2011141414, 2011; i) M. El Qacemi, H. Smits, J. Y. Cassayre,
N. P. Mulholland, P. Renold, E. Godineau, T. Pitterna,
WO2011154555, 2011; j) T. Murata, K. Araki, H. Kishikawa,
H. Watanabe, N. Sasaki, E. Shimojo, T. Ichihara, K. Shibuya, U.
[9] H. Kawai, T. Kitayama, E. Tokunaga, T. Matsumoto, H. Sato, M.
[10] A similar cinchona alkaloid/thiourea catalysis was independ-
ently patented by the Syngenta group, but the generality of
substrates is very limited. See, Ref. [4i].
[11] a) C. E. Song, Cinchona Alkaloids in Synthesis & Catalysis:
Ligands, Immobilization and Organocatalysis, Wiley-VCH,
Weinheim, 2009; b) E. M. O. Yeboah, S. O. Yeboah, G. S.
[12] a) Y. Liu, B. A. Provencher, K. J. Bartelson, L. Deng, Chem. Sci.
5578
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 5575 –5579