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In summary, we have developed a Pd-catalyzed asymmetric
allylic alkylation of azlactones with 4-arylvinyl-1,3-dioxolan-2-
ones to give “branched” chiral alkylated α-amino acid products
with vicinal tertiary and quaternary stereocenters. The products
can be obtained in high yields and with excellent regio-, diastero-,
and enantioselectivities. Mechanistic studies suggested that the
excellent regioselectivity of our alkylation is determined by a
hydrogen bond formed between the Pd-allylic complex and
azlactone isomer. Additionally, the alkylation can be performed
on a gram scale without a loss of enantioselectivity, and the
resulting product can be further transformed to a chiral azetidine
in two simple steps.
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(7) Only a few examples for which Pd-catalyzed asymmetric allylic
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
(8) We have been carrying out research in this area using vinyl-1,3-
dioxolan-2-ones as allylic substrates since 2008: (a) Shen, K.; Zhao, L.;
Zhao, C. National University Student Innovation Program (SJTU), No.
S170ITP3001. (b) Quan, M.; Butt, N. A.; Shen, J.; Shen, K.; Liu, D.;
Zhang, W. Org. Biomol. Chem. 2013, 11, 7412.
(9) (a) Zhao, X.; Liu, D.; Guo, H.; Liu, Y.; Zhang, W. J. Am. Chem. Soc.
2011, 133, 19354. (b) Huo, X.; Quan, M.; Yang, G.; Zhao, X.; Liu, D.;
Liu, Y.; Zhang, W. Org. Lett. 2014, 16, 1570. (c) Huo, X.; Yang, G.; Liu,
D.; Liu, Y.; Gridnev, I. D.; Zhang, W. Angew. Chem., Int. Ed. 2014, 53,
6776.
(10) For reviews, see: (a) Zhang, J.; Zhang, Y. J.; Zhang, W. Chin. J. Org.
Chem. 2007, 27, 1089. (b) Li, Y.; Zheng, Y.; Tian, F.; Zhang, Y. J.; Zhang,
W. Chin. J. Org. Chem. 2009, 29, 1487. (c) Zhang, W.; Liu, D. In Chiral
Ferrocenes in Asymmetric Catalysis: Synthesis and Applications, Vol. 14;
Dai, L.-X., Hou, X.-L., Eds.; VCH: Weinheim, Germany, 2010; pp 175−
214. (d) Butt, N. A.; Liu, D.; Zhang, W. Synlett 2014, 25, 615. (e) Butt,
N. A.; Zhang, W. Chem. Soc. Rev. 2015, 44, 7929.
Experimental section and copies of NMR and HPLC
AUTHOR INFORMATION
Corresponding Author
■
Author Contributions
§XW and DL contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partially supported by the National Natural
Science Foundation of China (Nos. 21172143, 21172145,
21372152, and 21232004), Science and Technology Commis-
sion of Shanghai Municipality (No. 14XD1402300), and Nippon
Chemical Industrial Co., Ltd. We gratefully acknowledge Dr.
Masashi Sugiya and Professor Tsuneo Imamoto of Nippon
Chemical Industrial Co., Ltd. for helpful discussions and the
Instrumental Analysis Center of SJTU for characterization.
(11) For reviews, see: (a) Vogl, E. M.; Groger, H.; Shibasaki, M. Angew.
̈
Chem., Int. Ed. 1999, 38, 1570. (b) Zhu, S.-F.; Zhou, Q.-L. Acc. Chem.
Res. 2012, 45, 1365.
(12) CCDC 1052610 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
(14) (a) Yoda, H. Curr. Org. Chem. 2002, 6, 223. (b) Brandi, A.; Cicchi,
S.; Cordero, F. M. Chem. Rev. 2008, 108, 3988. (c) Bott, T. M.; West, F.
G. Heterocycles 2012, 84, 223. (d) Bach, T. M. H.; Takagi, H. Appl.
Microbiol. Biotechnol. 2013, 97, 6623.
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