文献类型：期刊文献

英文题名：Chiral N,O-Ligand/[Cu(OAc)2]-Catalyzed Asymmetric Construction of 4-Aminopyrrolidine Derivatives by 1,3-Dipolar Cycloaddition of Azomethine Ylides with -Phthalimidoacrylates

作者：Wang, Zheng[1];Yu, Xingxin[1];Tian, Bo-Xue[2];Payne, Daniel T.[3];Yang, Wu-Lin[1];Liu, Yang-Zi[1];Fossey, John S.[3];Deng, Wei-Ping[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94158 USA;[3]Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England

年份：2015

卷号：21

期号：29

起止页码：10457

外文期刊名：CHEMISTRY-A EUROPEAN JOURNAL

收录：;EI(收录号：20152400926801);WOS:【SCI-EXPANDED(收录号:WOS:000357328200027)，CCR-EXPANDED(收录号:WOS:000357328200027)】；

基金：This work is supported by The Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (No. 21172068, No. 21402049), Shanghai Pujiang Program (No. 14PJD013), and Shanghai Yangfan Program (No. 14YF1404600). J.S.F. thanks ECUST for a guest professorship. J.S.F. and D.T.P. thank the University of Birmingham for support, including travel awards and a PhD studentship (D.T.P.). The Catalysis and Sensing for our Environment (CASE) consortium are thanked for networking opportunities.

语种：英文

外文关键词：asymmetric synthesis; copper; cycloaddition; density functional calculations; ligands

摘要：A protocol to access useful 4-aminopyrrolidine-2,4-dicarboxylate derivatives has been developed. A variety of chiral N,O-ligands derived from 2,3-dihydroimidazo[1,2-a]pyridine motifs have been evaluated in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides to -phthalimidoacrylates. Reactions catalyzed by copper in combination with ligand 7-Cl-DHIPOH provided the highest level of stereoselectivity for the 1,3-dipolar cycloaddition reaction. The reaction tolerates both -substituted and -unsubstituted -phthalimidoacrylate as dipolarophiles, affording the corresponding quaternary 4-aminopyrrolidine cycloadducts with excellent diastereo- (>98:2d.r.) and enantioselectivities (up to 97%ee). Removal of the phthalimido protecting group can be accomplished by a simple NaBH4 reduction. Theoretical calculations employing DFT methods show this cycloaddition reaction is likely to proceed through a stepwise mechanism and the stereochemistry was also theoretically rationalized.