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25September2017

Prof. Qi-Lin Zhou's Research Group

周其林教授课题组主页

Can-Ming Zhang (张灿明)

EDUCATION

2002.9 - 2006.6 Nankai University, College of Chemistry, B. S.    

2006.9 - 2009.7 Nankai University, SKLEOC, M. S.  

CONTACT

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DISSERTATION

<Synthesis and application of new chiral phosphino/oxazoline ligand>

Abstract

    The design and synthesis of chiral ligands plays crucial role in transition metal-catalyzed asymmetric synthesis. Chiral phosphino-oxazoline ligands, which coordinate to a metal center with a N- and a P-atom, allow effective enantiocontrol in a variety of metal-catalyzed reactions. Recently, we developed a series of chiral spiro phosphine-oxazoline-ligands and successfully applied them in iridium-catalyzed highly enantioselective hydrogenation reactions. Since we use chiral amino alcohols to construct the oxazoline moieties of the spiro phosphino-oxazoline ligands, there are four isomers for each ligand, which puzzled the analysis as well as applications of the ligands in asymmetric catalysis. In the same time, steric effect of substituted oxazoline limits the scope of substrates. Moreover, the optical pure amino acids increase the cost for preparation of the ligands.

    In this thesis, we prepared a chiral spiro phosphine-oxazoline ligands containing only a chirality on scaffold starting with enatiomerically pure 1,1'-spiro- biindane-7,7'-diol (SPINOL) and readily available 2-aminoethanol. We then applied the iridium complexes of the novel spiro phosphino-oxazoline ligand  in asymmetric hydrogenation of an a-isopropylcinnamic acid to preparation the key intermediate for the synthesis of new blood pressure-lowering drug Aliskiren. The exceptional high reactivity (TON = 10,000) as well as enantioselectivity (95%) was obtained under very mild reaction conditions. This primary result was superior to those reported previously. It provides great potential utility of the catalytic asymmetric hydrogenation in larger scale synthesis. Based on these results, we further applied the spiro phosphino-oxazoline ligand in iridium catalyzed asymmetric hydrogenation of a-phenylcinnamic acids. Once again, high enantioselectivities were obtained for a broad range of substrates under very mild conditions. It provids a efficient approache for preparation of a,b-diphenylpropionic acids.

    8 new compounds were synthesized and identified by 1H NMR, 13C NMR, HRMS analysis in this context.

Keywords: phosphine-oxazoline ligands,  iridium complexes,  catalytic asymmetric hydrogenation,  unsaturated carboxylic acids

PUBLICATION

1.Shen Li, Shou-Fei Zhu, Jian-Hua Xie, Song Song, Can-Ming Zhang, and Qi-Lin Zhou*, Enantioselective hydrogenation of α-aryloxy and α-alkoxy α,β-unsaturated carboxylic acids catalyzed by chiral spiro iridium/phosphino-oxazoline complexes, J. Am. Chem. Soc. 2010132, 1172-1179.

2.Shen Li, Shou-Fei Zhu, Can-Ming Zhang, Song Song, Qi-Lin Zhou*, Iridium-catalyzed enantioselective hydrogenation of α,β-unsaturated carboxylic acids,J. Am. Chem. Soc. 2008130, 8584-8585.

3.Yi-Xia Jia, Jun Zhong, Shou-Fei Zhu, Can-Ming Zhang, Qi-Lin Zhou*, Chiral Βrønsted acid catalyzed enantioselective Friedel-Crafts reaction of indoles and α-aryl enamides: construction of chiral quaternary carbons, Angew. Chem. Int. Ed.200746, 5565-5567.