EDUCATION

2000.9 - 2004.6 Nankai University, College of Chemistry, B. S.

2004.9 - 2009.6 Nankai University, SKLEOC, Ph. D.

2010.9 - Now      University of Illinois at Chicago

CONTACT

Tel: 314-780-9607

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Address: University of Illinois at Chicago, 2272 S Archer Ave Apt 4i, IL 60616

DISSERTATION

< a-胺基酮的不对称催化氢化反应及其应用研究>

Abstract

Chiral b-amino alcohols are essential structural units in natural products. They can be using as materials in the total synthesis of natural products and optical pharmacies. Moreover, optically pure amino alcohols have been used as chiral ligands and auxiliaries in asymmetric synthesis. In past decades, the synthesis of enantiomer-enriched chiral b-aminoalcohols attracted considerable attention and various methods for enantioselective and diastereoselective preparation of amino alcohols have been reported.The asymmetric hydrogenation of a-aminoketones is one of the most efficient methods to form chiral amino alcohols.According to the past document, most of the examples are limited to the synthesis of products with only one chiral center at the a-position. So the asymmetric hydrogenation of racemic a-amino ketones via dynamic kinetic resolution to form b-amino alcohols with chiral centers in both a- and b-position is a really challenge task.

By using ours spiro diphosphorus-ruthenium-diamine catalysts, we successfully asymmetric hydrogenated of all kinds of racemic a-amino ketones via dynamic kinetic resolution (DKR).  Excellent stereoselectivity (up to 99:1) with perfect enantioselectivity (up to 99.9% ee) was achieved. And the catalysts has a high activity, the turnover number is up to 30 000. We got the single crystal of our optical product, and the absolute configuration was determinate by X-ray diffraction. To explain the high selectivity achieved in the hydrogenation reaction, we proposed a transition state model (TS) based on hydrogenation bond.

By using chiral b-amino alcohols as materials, we successfully developed a new method for synthesis of optically purity trans-1,2-diamine. We also used this method to total synthesis of a highly selective k-opioid agonist U-(-)-50488. And the asymmetric hydrogenation can be used in the total synthesis of natural alkaloid (-)-a-conhydrine and (+)-b-conhydrine.

In this study, 13 new compounds were synthesized and confirmed by ¹H NMR, ¹³C NMR, Elmento-analysis, MS or HRMS analysis.

Keywords:b-amino alcohols, catalytic asymmetric hydrogenation, dynamic kinetic resolution (DKR), diphosphorus-ruthenium-diamine catalysts

PUBLICATION

1.Wen-Ju Bai, Jian-Hua Xie, Ya-Li Li, Sheng Liu, Qi-Lin Zhou*, Enantioselective synthesis of chiral β-aryloxyalcohols by ruthenium- catalyzed ketone hydrogenation via DKR, Adv. Synth. Catal. 2010, 352, 81-84.

2.Sheng Liu, Jian-Hua Xie, Wei Li, Wei-Ling Kong, Li-Xin Wang, Qi-Lin Zhou*, Highly enantioselective synthesis of chiral cyclic amino alcohols and conhydrine by ruthenium-catalyzed asymmetric hydrogenation, Org. Lett. 2009, 11, 4994-4997.

3.Jian-Hua Xie, Sheng Liu, Wei-Ling Kong, Wen-Jun Bai, Xiao-Chen Wang, Li-Xin Wang, Qi-Lin Zhou*, Highly enantioselective and diastereoslective synthesis of chiral amino alcohols by ruthenium-catalyzed asymmetric hydrogenation of α-amino aliphatic ketones, J. Am. Chem. Soc. 2009, 131, 4222-4223.

4. Sheng Liu, Jian-Hua Xie, Li-Xin Wang, Qi-Lin Zhou*, Dynamic kinetic resolution allows α highly enantioselective synthesis of cis--aminocycloalkanols by ruthenium-catalyzed asymmetric hydrogenation, Angew. Chem. Int. Ed. 2007, 46, 7506-7508.

5.Jian-Hua Xie, Sheng Liu, Xiang-Hong Huo, Xu Cheng, Hai-Feng Duan, Bao-Ming Fan, Li-Xin Wang, Qi-Lin Zhou*, Ru(II)-SDP-complexes catalyzed asymmetric hydrogenation of ketones. The effect of alkali metal cation in the reaction,J. Org. Chem.2005, 70, 2967-2973.