EDUCATION

1999.9 - 2003.7  East China University of Technology, B. S.

2003.9 - 2008.1  East China University of Technology, Ph. D.

CONTACT

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Address: China Novartis Institutes for BioMedical Research Co.

DISSERTATION

–H bond Insertion and Michael Addition Reactions>

Abstract

With forty years development, transition metal catalyzed asymmetric synthesis plays an important role in the preparation of chiral compounds, with the design and synthesis of new chiral ligands as its main focus. By now, many efficient ligands were synthesized and applied in various asymmetric reactions. Due to the advantages such as largely available in enantiomerically pure form and widely varied complexation with transition metals, the nitrogen-containing ligands attracted a great attention in asymmetric catalysis. The aim of this thesis is to study the applications of nitrogen-containing ligands with a chiral spirobiindane skeleton.

Spiro bisoxazoline ligands were found highly efficient in copper-catalyzed asymmetric O–H insertion reactions. The enantioselective insertion of carbenoids into O–H bonds of phenols yielded α-aryloxycarboxylic esters in high yields with enantioselectivities of up to 99.6% ee, which provides a new approach to the enantioselective synthesis of chiral α-aryloxycarboxylic esters and acids.

By using copper complexes of spiro bisoxazoline ligands, we have developed the first highly enantioselective catalytic insertion of α-diazoesters into O–H bond of water,producting α-hydroxy esters in high yields with enantioselectivities of up to 94% ee.

In addition to phenols and water, aliphatic alcohols and carboxylic acid also underwent O–H insertion reaction with good yields and moderate enantiomeric excesses. The successful use of spiro bisoxazolines in the asymmetric insertion of O–H bonds indicates a high potential of these novel nitrogen ligands in asymmetric insertion reactions of heteroatom-hydrogen bond (X–H) of a wide range of substrates.

Furthermore, a series of chiral spiro pyridine-containing ligands were conveniently prepared from 1,1'-spirobiindane-7,7'-diol (Spinol) in high yields. The cobalt complexes prepared in situ from Co(OAc)₂and the ligands have been proven to be efficient catalysts for the asymmetric Michael addition reaction of malonates to chalcone derivatives. The Michael addition products were obtained in high yields with moderate enantiomeric excesses.

Thirty-four new compounds were synthesized in this thesis. Their structures were identified by ¹H NMR, ¹³C NMR, MS, HRMS or elemental analysis.

Key words: asymmetric catalysis, nitrogen-containing ligands, O–H insertion, Michael addition

PUBLICATION

1.Shou-Fei Zhu, Chao Chen, Yan Cai, Qi-Lin Zhou*, Catalytic asymmetric reaction with water: Enantioselective synthesis of α-hydroxyesters by copper-carbenoid O–H insertion reaction, Angew. Chem. Int. Ed. 2008, 47, 932-934.

2. Chao Chen, Shou-Fei Zhu, Βin Liu, Li-Xin Wang, Qi-Lin Zhou*, Highly enantioselective insertion of carbenoids into O–H bonds of phenols: An efficient approach to chiral α-aryloxycarboxylic esters, J. Am. Chem. Soc. 2007, 129, 12616-12617.

3.Bin Liu, Shou-Fei Zhu, Wei Zhang, Chao Chen, Qi-Lin Zhou*, Highly enantioselective insertion of carbenoids into N-H bonds catalyzed by copper complexes of chiral spiro bisoxazolines, J. Am. Chem. Soc. 2007, 129, 5834-5835.

4. Chao Chen, Shou-Fei Zhu, Xin-Yan Wu*, Qi-Lin Zhou*, Preparation and application of chiral spiro nitrogen-containing ligands for cobalt-catalyzed asymmetric Michael addition, Tetrahedron: Asymmetry 2006, 17, 2761-2767.