Organic Letters
Letter
Serafino, R.; Strathdee, C. A.; Turci, S. M.; Wilson, C.; DiMauro, E. F.
J. Med. Chem. 2013, 56, 4320.
Compound 8 can be used as a key intermediate for the
construction of several biologically active compounds, such as
the cannabinoid receptor 1 inhibitor 9,9a the TNF activity
moderator 10,9b the bioactive tankyrase inhibitor 11,2c and the
plant growth regulating compound 12.9c
(3) For the synthesis of chiral α,β-unsaturated γ-amino esters, see:
(a) Lee, J. H.; Lee, S.-G. Chem. Sci. 2013, 4, 2922. (b) Pedersen, T. M.;
Hansen, E. L.; Kane, J.; Rein, T.; Helquist, P.; Norrby, P.-O.; Tanner,
D. J. Am. Chem. Soc. 2001, 123, 9738. (c) Srikanth, G.; Ramakrishna,
K. V. S.; Sharma, G. V. M. Org. Lett. 2015, 17, 4576. (d) Zhang, M.;
Watanabe, K.; Tsukamoto, M.; Shibuya, R.; Morimoto, H.; Ohshima,
T. Chem. - Eur. J. 2015, 21, 3937. (e) Kondoh, A.; Kamata, Y.; Terada,
M. Org. Lett. 2017, 19, 1682.
To further explore the utility of chiral γ-lactams in organic
synthesis, 3ae bearing a para-substituted bromine atom on the
phenyl ring was converted to its corresponding chiral γ-lactam
13 in high yield (Scheme 7). Compound 13 could be further
transformed to 14 (a candidate for the treatment of
inflammatory disorders)10a or a hydroxamate-based inhibitor
of deacetylases B 15 following literature procedures.10b
In summary, we have developed a Pd-catalyzed asymmetric
allylic amination of 4-substituted 2-acetoxybut-3-enoates with
different amines for the synthesis of chiral α,β-unsaturated γ-
amino esters. The desired products can be obtained in up to
98% yield and with more than 99% ee and can be transformed
to chiral γ-amino acid/alcohol derivatives and chiral γ-lactams,
which can be further applied to the synthesis of several types of
chiral drugs and drug candidates. The preferential formation of
γ-amino esters over α-amino esters has been discussed. This
work provides an efficient strategy for the synthesis of chiral γ-
substituted α,β-unsaturated γ-amino esters.
(4) Selected reviews of Pd-catalyzed asymmetric allylic substitutions,
see: (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395.
(b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336. (c) Trost,
B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921. (d) Lu, Z.; Ma, S.
Angew. Chem., Int. Ed. 2008, 47, 258. (e) Trost, B. M.; Zhang, T.;
Sieber, J. D. Chem. Sci. 2010, 1, 427. (f) Trost, B. M. Org. Process Res.
Dev. 2012, 16, 185. (g) Oliver, S.; Evans, P. A. Synthesis 2013, 45,
3179. (h) Butt, N.; Zhang, W. Chem. Soc. Rev. 2015, 44, 7929.
(i) Grange, R. L.; Clizbe, E. A.; Evans, P. A. Synthesis 2016, 48, 2911.
(j) Butt, N.; Yang, G.; Zhang, W. Chem. Rec. 2016, 16, 2687.
(5) Selected our recent papers, see: (a) Zhao, X.; Liu, D.; Guo, H.;
Liu, Y.; Zhang, W. J. Am. Chem. Soc. 2011, 133, 19354. (b) Quan, M.;
Butt, N.; Shen, J.; Shen, K.; Liu, D.; Zhang, W. Org. Biomol. Chem.
2013, 11, 7412. (c) Huo, X.; Quan, M.; Yang, G.; Zhao, X.; Liu, D.;
Liu, Y.; Zhang, W. Org. Lett. 2014, 16, 1570. (d) Huo, X.; Yang, G.;
Liu, D.; Liu, Y.; Gridnev, I. D.; Zhang, W. Angew. Chem., Int. Ed. 2014,
53, 6776. (e) Wei, X.; Liu, D.; An, Q.; Zhang, W. Org. Lett. 2015, 17,
5768. (f) Huo, X.; He, R.; Zhang, X.; Zhang, W. J. Am. Chem. Soc.
2016, 138, 11093. (g) Yao, K.; Liu, D.; Yuan, Q.; Imamoto, T.; Liu, Y.;
Zhang, W. Org. Lett. 2016, 18, 6296. (h) An, Q.; Liu, D.; Shen, J.; Liu,
Y.; Zhang, W. Org. Lett. 2017, 19, 238.
ASSOCIATED CONTENT
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S
* Supporting Information
The Supporting Information is available free of charge on the
(7) Yuan, Q.; Liu, D.; Zhang, W. Org. Lett. 2017, 19, 1886.
(8) (a) Bellesia, F.; Clark, A. J.; Felluga, F.; Gennaro, A.; Isse, A. A.;
Roncaglia, F.; Ghelfi, F. Adv. Synth. Catal. 2013, 355, 1649. (b) Fenster,
E.; Hill, D.; Reiser, O.; Aube, J. Beilstein J. Org. Chem. 2012, 8, 1804.
́
(c) Tan, D. Q.; Atherton, A. L.; Smith, A. J.; Soldi, C.; Hurley, K. A.;
Fettinger, J. C.; Shaw, J. T. ACS Comb. Sci. 2012, 14, 218.
Experimental procedures, characterization details, and
AUTHOR INFORMATION
Corresponding Authors
■
(9) (a) Alexander, R. P.; Brace, G. N.; Brown, J. A.; Calmiano, M. D.;
Chovatia, P. T.; Deligny, M.; Gallimore, E. O.; Heer, J. P.; Jackson, V.
E.; Kroeplien, B.; Maccoss, M.; Quincey, J. R.; Sabnis, Y. A.; Swinnen,
D. L. L.; Zhu, Z. Fused tricyclic imidazole derivatives as modulators of
TNF acitivity. EP 2014076884, 2015. (b) Villedieu-PerCheron, E.;
Lachia, M. D.; De Mesmaeker, A.; Wolf, H. C.; Jung, P. J. M.; Lanfer-
Meijer, F.; Van Den Wijingaard, P.; Screpanti, C. Plant growth
regulating compounds. EP 2013060470, 2013. (c) Liu, H.; He, X.;
Phillips, D.; Yang, K.; Lau, T.; Wu, B.; Xie, Y.; Nguyen, T. N.; Wang,
X. Compounds and compositions as inhibitors of Cannabinoid
receptor 1 activity. US 2007087230, 2010.
(10) (a) Kozlowski, J. A.; Yu, W. S.; Wong, M. K. C.; Kim, S.-H.;
Tong, L.; Lavey, B. J.; Shankar, B. B.; Yang, D. Y.; Feltz, R.; Kosinski,
A. M.; Zhou, G. W.; Rizvi, R. K.; Dai, C. Y.; Fire, L.; Girijavallabhan, V.
M.; Li, D. S.; Popovici-Muller, J.; Richard, J. E.; Kristin, K. E.; Siddiqui,
M. A.; Yang, L. P. Compounds for the treatment of inflammatory
disorders. WO 2010054279 A1, 2010. (b) Shultz, M.; Chen, C. H.-T.;
Cho, Y. S.; Jiang, L.; Fan, J. M.; Liu, G.; Majumdar, D. Hydroxamate-
based inhibitors of deacetylases. WO 2009118305 A1, 2009.
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was partially supported by the National Natural
Science Foundation of China (Nos. 21372152, 21402117,
21672142, and 21232004), the Basic Research Foundation of
Shanghai Committee of Science and Technology
(15JC1402200), and the Instrumental Analysis Center of
SJTU for characterization. We also thank Prof. Ilya Gridnev and
Masahiro Terada of Tohoku University, Japan, for their helpful
discussions.
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