EDUCATION 

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

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

CONTACT   

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Address: Building E, No. 29 Life Science Park Road, Changping District, Beijing, 102206, P.R. China

DISSERTATION

< 钯催化醛、酮和亚胺的不对称烯丙基化反应研究> 

Abstract 

Enantioselective allylation of aldehydes, ketones and imines represents one of the most efficient strategies for the preparation of chiral homoallylic alcohols and amines, which are of high importance in organic synthesis. Remarkable progress has been achieved in the enantioselective allylation mainly by the use of allylic metal compounds as allylating reagents. However, the allylic metals suffer from many drawbacks such as air and moisture sensitivity, the need of a multi-step preparation, and some metal compound such as allylstannanes, are highly toxic. Thus, the search for more stable and available allylating reagents is one of the major tasks for this important transformation. In this dissertation, we demonstrated palladium-catalyzed asymmetric allylation of aldehydes, ketones and imines with allylic alcohols as allylating reagents by using chiral spiro monodentate phosphorous ligands. 

By using sterically hindered chiral monodentate spiro phosphite ligands, we have realized the first highly enantioselective palladium-catalyzed allylation of aldehydes with allylic alcohols to produce homoallylic alcohols with high yields and excellent enantioselectivities ( up to 97% ee). These results represent the highest level of enantioselectivities for the reaction with allylic alcohols and arecomparable to the best results achieved with allylic metal reagents. Under the optimal reaction conditions, the allylation of wide scope of aromatic and aliphatic aldehydes with simple allylic alcohol and various 2-substituted allylic alcohols was accomplished with good yields and high enantioselectivities. Besides allylic alcohols, a number of readily available allylation reagents such as allylic halides and allylic esters have also been applied in the asymmetric allylation of aromatic aldehydes with excellent enantioselectivities (up to 96% ee). We proposed a new allylic palladium “umploung” mechanism, and demonstrated that only one chiral ligand coordinates to palladium in the chiral induction step based on “non-linear effect” experiment. We rationalized the chiral induction based on the crystal structure of palladium complex of chiral spiro monodentate phosphate ligand and the absolute configuration of allylating products. 

We then developed a palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as allyl donor by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols, 3-allyl-3-hydroxy-2-oxindoles, were prepared directly from allylic alcohols with excellent yields and moderate to good enantioselectivities (46–71% ee). It is the first catalytic asymmetric allylation of ketones with allylic alcohol as allylating agent.

 Finally, we have realized a palladium-catalyzed asymmetric allylation of imines with allylic alcohols as allyl donor by using chiral spiro phosphoramidite ligands. The homoallylic amines were obtained in high yields with good enantioselectivities (up to 80% ee). It represents the first catalytic asymmetric allylation of imines with non-metal allylating reagents.

Key words: palladium-catalysis, spiro monodentate phosphorous ligand, allylic alcohol, asymmetric allylation, aldehydes, ketones, imines.

PUBLICATION

1.Xiang-Chen Qiao, Shou-Fei Zhu, Wang-Qiao Chen, and Qi-Lin Zhou*, Palladium-catalyzed asymmetric umpolung allylation of imines with allylic alcohols, Tetrahedron: Asymmetry 2010, 21, 1216-1220.

2. Xiang-Chen Qiao, Shou-Fei Zhu, Qi-Lin Zhou*, From allylic alcohols to chiral tertiary homoallylic alcohol: palladium-catalyzed asymmetric allylation of isatins, Tetrahedron: Asymmetry 2009, 20, 1254-1261.

3.Hai-Feng Duan, Jian-Hua Xie, Xiang-Chen Qiao, Li-Xin Wang, Qi-Lin Zhou*, Enantioselective rhodium-catalyzed addition of arylboronic acids to α-ketoesters, Angew. Chem. Int. Ed. 2008, 47, 4351-4353.

4.Qi Zhang, Shou-Fei Zhu, Xiang-Chen Qiao, Li-Xin Wang, Qi-Lin Zhou*, Nickel-catalyzed highly selective hydrovinylation of α-ketals of vinylarenes, Adv. Synth. Catal. 2008, 350, 1507-1510.

5.Wei Zhang, Shou-Fei Zhu, Xiang-Chen Qiao, Qi-Lin Zhou*, Highly enantioselective copper-catalyzed ring opening of oxabicyclic alkenes with Grignard reagents, Chem. Asian J. 2008, 3, 2105-2111.

6.Xu Cheng, Shou-Fei Zhu, Xiang-Chen Qiao, Pu-Cha Yan, Qi-Lin Zhou*, Α general synthetic route to chiral dihydroxy-9,9'-spirobifluorenes, Tetrahedron 2006, 62, 8077-8082.