Organic Letters
Letter
B. K. S.; Lee, M. C. S.; Zou, B.; Russell, B.; Seitz, P.; Plouffe, D. M.;
spirocyclic compound 5. The Boc group could be selectively
deprotected with 3 N HCl in dioxane at 60 °C to deliver the
corresponding (S)-spiro[indoline-3,1′-isoindolin]-2-one 6 with
no erosion of optical purity. This showcases a unique
advantage of our method, as such spirocyclic molecules are
otherwise difficult to access particularly in a highly stereo-
selective manner.
In summary, we have developed an efficient rhodium-
catalyzed enantioselective arylation of isatin-derived N-Boc
ketimines using an exceptionally simple chiral phosphite-olefin
as ligand. The method exhibits broad substrate generality and
functional group tolerance, enabling ready access to a wide
variety of valuable 3-aryl-3-aminooxindoles bearing a stereo-
defined quaternary carbon center in moderate to good yields
(up to 98%) with excellent enantioselectivities (up to 98% ee).
Significantly, these versatile products can be conveniently
transformed into a range of biologically interesting complex
molecules. Further efforts on exploring the application of this
practical method in related biological and drug discovery
studies are underway in our laboratory.
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Dharia, N. V.; Tan, J.; Cohen, S. B.; Spencer, K. R.; Gonzalez-Paez, G.
E.; Lakshminarayana, S. B.; Suwanarusk, A. R.; Jegla, T.; Schmitt, E.
K.; Beck, H.-P.; Brun, R.; Nosten, F.; Renia, L.; Dartois, V.; Keller, T.
H.; Fidock, D. A.; Winzeler, E. A.; Diagana, T. T. Science 2010, 329,
1175. (i) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945.
(j) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2003, 2209.
(k) Trost, B. M.; Brennan, M. K. Synthesis 2009, 2009, 3003.
(l) Zhou, F.; Liu, Y.-L.; Zhou, J. Adv. Synth. Catal. 2010, 352, 1381.
(m) Singh, G. S.; Desta, Z. Y. Chem. Rev. 2012, 112, 6104.
(n) Chauhan, P.; Chimni, S. S. Tetrahedron: Asymmetry 2013, 24, 343.
(o) Zhang, M. Z.; Chen, Q.; Yang, G.-F. Eur. J. Med. Chem. 2015, 89,
421. (p) Sherer, C.; Snape, T. Eur. J. Med. Chem. 2015, 97, 552.
(2) (a) Griebel, G.; Simiand, J.; Serradeil-LeGal, C.; Wagnon, J.;
Pascal, M.; Scatton, B.; Maffrand, J.-P.; Soubrie, P. Proc. Natl. Acad.
Sci. U. S. A. 2002, 99, 6370. (b) Gilles, G.; Claudine, S. L. Stress 2003,
6, 199. (c) Oost, T.; Backfisch, G.; Bhowmik, S.; van Gaalen, M. M.;
Geneste, H.; Hornberger, W.; Lubisch, W.; Netz, A.; Unger, L.;
Wernet, W. Bioorg. Med. Chem. Lett. 2011, 21, 3828.
(3) (a) Yeung, B. K. S.; Zou, B.; Rottmann, M.; Lakshminarayana, S.
B.; Ang, S. H.; Leong, S. Y.; Tan, J.; Wong, J.; Keller-Maerki, S.;
Fischli, C.; Goh, A.; Schmitt, E. K.; Krastel, P.; Francotte, E.; Kuhen,
K.; Plouffe, D.; Henson, K.; Wagner, T.; Winzeler, E. A.; Petersen, F.;
Brun, R.; Dartois, V.; Diagana, T. T.; Keller, T. H. J. Med. Chem.
2010, 53, 5155. (b) Duce, S.; Pesciaioli, F.; Gramigna, L.; Bernardi,
L.; Mazzanti, A.; Ricci, A.; Bartoli, G.; Bencivenni, G. Adv. Synth.
Catal. 2011, 353, 860. (c) Badillo, J. J.; Silva-García, A.; Shupe, B. H.;
Fettinger, J. C.; Franz, A. K. Tetrahedron Lett. 2011, 52, 5550. (d)
Leugn, C.; Tomaszewski, M.; Woo, S. (Astrazeneca AB Swed) U.S.
Patent. 2007185179, 2007.
(4) (a) Baroni, M.; Puleo, L. (Sanofi-Aventis, FR) WO/2009/
056707. (b) Puleo, L.; Marini, P.; Avallone, R.; Zanchet, M.;
Bandiera, S.; Baroni, M.; Croci, T. Bioorg. Med. Chem. 2012, 20, 5623.
(5) (a) Cheng, L.; Liu, L.; Wang, D.; Chen, Y.-J. Org. Lett. 2009, 11,
3874. (b) Bui, T.; Hernandez-Torres, G.; Milite, C.; Barbas, C. F. Org.
Lett. 2010, 12, 5696. (c) Yang, Z.; Wang, Z.; Bai, S.; Shen, K.; Chen,
D.; Liu, X.; Lin, L.; Feng, X. Chem. - Eur. J. 2010, 16, 6632. (d) Zhou,
F.; Ding, M.; Liu, Y.-L.; Wang, C.-H.; Ji, C.-B.; Zhang, Y.-Y.; Zhou, J.
Adv. Synth. Catal. 2011, 353, 2945.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental procedures and spectroscopic data of all
Accession Codes
CCDC 1403781 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(6) (a) Jia, Y. X.; Hillgren, J. M.; Watson, E. L.; Marsden, S. P.;
Kundig, E. P. Chem. Commun. 2008, 44, 4040. (b) Tolstoy, P.; Lee, S.
̈
AUTHOR INFORMATION
Corresponding Author
X. Y.; Sparr, C.; Ley, S. V. Org. Lett. 2012, 14, 4810.
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(7) (a) Feng, J.; Yan, W.; Wang, D.; Li, P.; Sun, Q.; Wang, R. Chem.
Commun. 2012, 48, 8003. (b) Chen, J.-P.; Chen, W.-W.; Li, Y.; Xu,
M.-H. Org. Biomol. Chem. 2015, 13, 3363. (c) Montesinos-Magraner,
ORCID
́
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M.; Vila, C.; Cantyn, R.; Blay, G.; Fernnadez, I.; Mun
Pedro, J. R. Angew. Chem., Int. Ed. 2015, 54, 6320. (d) Montesinos-
̃
oz, M. C.;
Notes
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o, A.; Blay, G.; Fernandez, I.;
Magraner, M.; Vila, C.; Rendon-Patin
Munoz, M. C.; Pedro, J. R. ACS Catal. 2016, 6, 2689. (e) Zhang, X.;
̃
The authors declare no competing financial interest.
Zhang, J.; Lin, L.; Zheng, H.; Wu, W.; Liu, X.; Feng, X. Adv. Synth.
Catal. 2016, 358, 3021. (f) Kaur, J.; Chimni, S. S. Org. Biomol. Chem.
2018, 16, 3328.
ACKNOWLEDGMENTS
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(8) (a) Jung, H. H.; Buesking, A. W.; Ellman, J. A. Org. Lett. 2011,
13, 3912. (b) He, Q.; Wu, L.; Kou, X.; Butt, N.; Yang, G.; Zhang, W.
Org. Lett. 2016, 18, 288. (c) Wang, J.-Y.; Li, M.-W.; Li, M.-F.; Hao,
W.-J.; Li, G.; Tu, S.-J.; Jiang, B. Org. Lett. 2018, 20, 6616. (d) Marques,
C. S.; Burke, A. J. Eur. J. Org. Chem. 2016, 2016, 806.
(9) For recent reviews, see: (a) Marques, C. S.; Burke, A. J.
ChemCatChem 2011, 3, 635. (b) Friestad, G. K.; Mathies, A. K.
Tetrahedron 2007, 63, 2541. (c) Chen, D.; Xu, M.-H. Chin. J. Org.
Chem. 2017, 37, 1589. For representative examples of Rh/Pd/Ni-
catalyzed addition of organoboron reagents to ketimines from other
groups, see: (d) Shintani, R.; Takeda, M.; Tsuji, T.; Hayashi, T. J. Am.
Chem. Soc. 2010, 132, 13168. (e) Nishimura, T.; Noishiki, A.; Tsui, G.
C.; Hayashi, T. J. Am. Chem. Soc. 2012, 134, 5056. (f) Nishimura, T.;
Noishiki, A.; Ebe, Y.; Hayashi, T. Angew. Chem., Int. Ed. 2013, 52,
1777. (g) Hepburn, H. B.; Lam, H. W. Angew. Chem., Int. Ed. 2014,
53, 11605. (h) Chen, Y.-J.; Chen, Y.-H.; Feng, C.-G.; Lin, G.-Q. Org.
Lett. 2014, 16, 3400. (i) Yang, G.; Zhang, W. Angew. Chem., Int. Ed.
We thank the National Science & Technology Major Project
“Key New Drug Creation and Manufacturing Program”, China
(2018ZX09711002-006) and the National Natural Science
Foundation of China (81521005, 21472205, 21325209) for
financial support.
REFERENCES
■
(1) (a) Zhang, X.; Smith, C. D. Mol. Pharmacol. 1996, 49, 228.
(b) Ochi, M.; Kawasaki, Y.; Kataoka, H.; Uchio, Y. Biochem. Biophys.
Res. Commun. 2001, 283, 1118. (c) Jensen, B. S. CNS Drug Rev. 2002,
8, 353. (d) Bernard, K.; Bogliolo, S.; Ehrenfeld, J. Br. J. Pharmacol.
2005, 144, 1037. (e) Ghosh, A. K.; Schiltz, G.; Perali, R. S.;
Leshchenko, S.; Kay, S.; Walters, D. E.; Koh, Y.; Maeda, K.; Mitsuya,
H. Bioorg. Med. Chem. Lett. 2006, 16, 1869. (f) Decaux, G.; Soupart,
A.; Vassart, G. Lancet 2008, 371, 1624. (g) Peddibhotla, S. Curr.
Bioact. Compd. 2009, 5, 20. (h) Rottmann, M.; McNamara, C.; Yeung,
D
Org. Lett. XXXX, XXX, XXX−XXX