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ChemComm
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COMMUNICATION
Journal Name
investigation on the influence of different α‐ and α'‐
2015, 54, 13711. (e) During the submissiDoOnI:o1f0o.1u0r39m/Can5CuCsc1r0i5p0t,2Aa
competitive work involving 1,6‐conjugate addition/aromatization
of para‐quinone methides with oxindoles has been reported: K.
Zhao, Y. Zhi, A. Wang, D. Enders, ACS Catal., 2016, 6, 657.
7 For selected reviews on organocatalysis based on bifunctional
(thio)ureas and squaramides, see: (a) S. J. Connon, Chem. Eur. J.,
2006, 12, 5418; (b) A. G. Doyle, E. N. Jacobsen, Chem. Rev., 2007,
107, 5713; (c) S. J. Connon, Chem. Commun., 2008, 2499; (d) Z.
Zhang, P. R. Schreiner, Chem. Soc. Rev., 2009, 38, 1187; (e) J.
Alemán, A. Parra, H. Jiang, K. A. Jørgensen, Chem. Eur. J., 2011,
17, 6890; (f) R. I. Storer, C. Aciro, L. H. Jones, Chem. Soc. Rev.,
2011, 40, 2330; (g) M. Tsakos, C. G. Kokotos, Tetrahedron, 2013,
69, 10199; (h) O. V. Serdyuk, C. M. Heckel, S. B. Tsogoeva, Org.
Biomol. Chem., 2013, 11, 7051; (i) T. J. Auvil, A, G. Schafer, A. E.
Mattson, Eur. J. Org. Chem., 2014, 2633; (j) P. Chauhan, S.
Mahajan, U. Kaya, D. Hack, D. Enders, Adv. Synth. Catal., 2015,
357, 253; (k) Y.‐L. Liu, J. Zhou, Synthesis, 2015, 47, 1210; (l) F.
Vetica, R. M. de Figueiredo, M. Orsini, D. Tofani, T. Gasperi,
Synthesis, 2015, 47, 2139; (m) F. E. Held, S. B. Tsogoeva, Catal.
Sci. Technol., 2016, 6, 645.
8 For chiral bis‐squaramides 4h4j, see: (a) C.; Sogn, J. Lee, T. Ryu,
H. Bae, J. Oh, WO 2010131881, 2010; (b) J. W. Lee, T. H. Ryu, J. S.
Oh, H. Y. Bae, H. B. Jang, C. E. Song, Chem. Commun., 2009, 7224.
9 Some examples using bis‐Cinchona‐based squaramides as
catalyst have been elegantly reported. For the asymmetric
resolutions, see ref. [8] and (a) J. S. Oh, K. II Kim, C. E. Song, Org.
Biomol. Chem., 2011, 9, 7983; (b) P. Renzi, C. Kronig, A. Carlone,
S. Eröksüz, A. Berkessel, M. Bella, Chem. Eur. J., 2014, 20, 11768;
(c) S. Tallon, F. Manoni, S. J. Connon, Angew. Chem., Int. Ed.,
2015, 54, 813. For the methanolysis of anhydrides, see: (d) E. H.
Nam, S. E. Park, J. S. Oh, S. Some, D. Y. Kim, H. Y. Bae, C. E. Song,
Bull. Korean Chem. Soc., 2011, 32, 3127. For 1,4‐conjugate
additions, see: (e) W. Yang, D.‐M. Du, Chem. Commun., 2011, 47,
12706; (f) S. Žari, T. Kailas, M. Kudrjashova, M. Öeren, I. Järving,
T. Tamm, M. Lopp, T. Kanger, Beilstein J. Org. Chem., 2012, 8,
1452; (g) N. Molleti, V. K. Singh, Org. Biomol. Chem., 2015, 13,
5243.
substituents in p‐QMs 1r–1t was pursued in the current
reaction. Despite somewhat decreased diastereocontrol (9:1
to >20:1 dr) in these cases, the excellent efficiency and
enantioselectivity (98% yield, 96–99% ee) were similarly
achieved for the formation of 3ra
controlled experiment using a stereoisomeric mixture of p‐QM
1u 1:1 dr) disclosed that both diastereo‐ and
–3ta. Importantly, the
(
enantiodiscrimination for the formation of 3ua (18:1 dr, 98%
ee) during 1,6‐addition were mostly independent of the
stereochemistry of the exocyclic methylene substituent of p‐
QM.
In conclusion,
a novel tertiary amine‐squaramide
catalyzed asymmetric 1,6‐conjugate addition of prochiral p‐
QMs with racemic oxindoles has been developed, in which a
new mode based on the bifunctional organocatalysis was
explored in the design of asymmetric catalytic methodology
related to para‐quinone methide chemistry. This methodology
provides an effective, diastereoselective and enantioselective
approach to the stereocontrolled synthesis of various
diarylmethine‐substituted oxindoles bearing vicinal tertiary
and quaternary stereocenters. The present reaction not only
explores the potential of the dimeric Cinchona‐derived
squaramides in asymmetric organocatalysis, but also enriches
the development of methodologies based on unique
bisvinylogous enone system of p‐QMs in asymmetric synthesis.
We are grateful for financial support from the NSFC
(21572083, 21322201, 21290180), the FRFCU (lzujbky‐2015‐
48), PCSIRT (IRT_15R28), the 111 Project of MOE of China
(111‐2‐17), and Chang Jiang Scholars Program (C.‐A. F.).
Notes and references
1 A. Baeyer, V. Villiger, Ber. Dtsch. Chem. Ges., 1903, 36, 2792.
2 For very recent reviews on the chemistry of p‐QMs, see: (a) A.
Parra, M. Tortosa, ChemCatChem, 2015, 7, 1524; (b) L. Caruana,
M. Fochi, L. Bernardi, Molecules, 2015, 20, 11733.
3 For recent selected examples, see: (a) R. Jansen, K. Gerth, H.
Steinmetz, S. Reinecke, W. Kessler, A. Kirschning, R. Müller,
Chem. Eur. J., 2011, 17, 7739; (b) P.‐H. Nguyen, B.‐T. Zhao, M. Y.
Ali, J.‐S. Choi, D.‐Y. Rhyu, B.‐S. Min, M.‐H. Woo, J. Nat. Prod.,
2015, 78, 34.
4 For recent selected examples, see: (a) C. Sridar, J. D'Agostino, P.
F. Hollenberg, Drug Metab. Dispos., 2012, 40, 2280; (b) A. K. F.
Albertson, J.‐P. Lumb, Angew. Chem., Int. Ed., 2015, 54, 2204; (c)
B. S. Matsuura, M. H. Keylor, B. Li, Y. Lin, S. Allison, D. A. Pratt, C.
R. Stephenson, Angew. Chem., Int. Ed., 2015, 54, 3754.
10 For details on the condition optimizations, see ESI.
11For the previous asymmetric synthesis of structurally
analogous diarylmethine‐substituted oxindoles with one
quaternary stereocenter (up to 82% ee), see: T. Zhang, Z.
Qiao, Y. Wang, N. Zhong, L. Liu, D. Wang, Y.‐J. Chen, Chem.
Commun., 2013, 49, 1636.
12The absolute configuration of 3ab (CCDC 1441998) was
determined by X‐ray crystallographic analysis, and
accordingly a plausible model for its enantioselectivity was
proposed tentatively. Under the C2‐symmetric bifunctional
catalysis of squaramide‐based dimeric Cinchona alkaloid
organocatalyst 4i, the Re face of p‐QM 1a was attacked
preferentially by the Re face of the enolate of oxindole 2b
,
5 For very recent selected examples on non‐asymmetric 1,6‐
addition of p‐QMs, see: (a) B. T. Ramanjaneyulu, S. Mahesh, R. V.
Anand, Org. Lett., 2015, 17, 3952; (b) V. Reddy, R. V. Anand, Org.
Lett., 2015, 17, 3390; (c) A. López, A. Parra, C. Jarava‐Barrera, M.
Tortosa, Chem. Commun., 2015, 51, 17684.
mostly due to the steric interaction.
6 For catalytic asymmetric 1,6‐addition of p‐QMs, see: (a) W.‐D.
Chu, L.‐F. Zhang, X. Bao, X.‐H. Zhao, C. Zeng, J.‐Y. Du, G.‐B. Zhang,
F.‐X. Wang, X.‐Y. Ma, C.‐A. Fan, Angew. Chem., Int. Ed., 2013, 52,
9229; (b) L. Caruana, F. Kniep, T. K. Johansen, P. H. Poulsen, K. A.
Jørgensen, J. Am. Chem. Soc., 2014, 136, 15929; (c) Y. Lou, P. Cao,
T. Jia, Y. Zhang, M. Wang, J. Liao, Angew. Chem., Int. Ed., 2015,
4 | J. Name., 2016, 00, 1‐3
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