Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (9): 1301-1306.DOI: 10.6023/A13040416 Previous Articles     Next Articles



谢承卫, 柏松, 宋宝安, 杨松   

  1. 贵州大学精细化工研究开发中心 绿色农药与农业生物工程国家重点实验室培育基地教育部绿色农药与生物工程重点实验室 贵阳 550025
  • 投稿日期:2013-04-17 发布日期:2013-05-24
  • 通讯作者: 宋宝安,,Tel:0086-0851-3620521;Fax:0086-0851-3622211,杨松,;
  • 基金资助:

    项目受国家重点基础研究发展计划项目(No. 2010CB126105)、国家自然科学基金重点项目(No. 21132003)和教育部长江学者创新团队发展计划 (No.[2011]20-IRT1057)资助.

Study of Mechanism to Asymmetric Mannich Reaction of Diethyl Malonate and Benzothiazol Imine Catalyzed by Applying Chiral Quinidine

Xie Chengwei, Bai Song, Song Baoan, Yang Song   

  1. Center for Research & Development of Fine Chemicals, State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering of Ministry of Education, Guizhou University, Guiyang 550025
  • Received:2013-04-17 Published:2013-05-24
  • Supported by:

    Project supported by the State Key Program for Basic Research of China (Grant No. 2010CB126105), the State Key Program of National Natural Science Foundation of China (Grant No. 21132003), and the Cheung Kong Scholars Innovation Team Development Plan of Ministry of Education of China (Grant No.[2011]20-IRT1057).

Benzothiazol-β-amino esters, acted as β-amino acids derivatives, perform excellent bioactivity in antibacterial and antivirus. To gain highly and purely optical single enantioisomer of benzothiazol-β-amino esters with simple organocatalyst, recently, the development for a classic Mannich reaction of diethyl malonate (Nu) with benzothiazol imine (EI) in the presence of cinchona alkaloid derivatives as organocatalyst has been made. The study for mechanism of applying unmodified cinchona alkaloid-chiral quinidine as potent organocatalyst to asymmetric Mannich reaction of benzothiazol-β-amino esters plays a vital role in asymmetric synthesis. In this work, the mechanism for Mannich reaction of benzothiazol-β-amino esters catalyzed by simple chiral quinidine organocatalyst was investigated through a combination of experiment with theoretical approaches (DFT). All geometry structures of reactants (Nu and EI), intermediates and product were optimized completely with the moderate approach M06-2X/6-311G (d,p) basis set in the gas phase. Afterward, the effect of solvent for DCM was took into consideration, and CPCM was used as polarization continuum model. Frequency calculations were performed at the same level of 6-311G (d,p) basis set as the geometry optimizations to confirm stable transition state (TS), which was verified further by means of IR vibrating frequency calculations (zero and only one imaginary frequency respectively). As comparison of (R)TS pathway with (S)TS pathway in potential energy profile, it enables to elaborate that (S)TS pathway executes to afford unique enatioisomer (S). The calculating results indicate that (1) Active sites of quinidine have been confirmed, that are 9-hydroxyl and tertiary amine; (2) The product exhibits S enantiomer as major configuration; (3) Moreover, the results of DFT calculation indicated that the stereo selectivity of the reaction could be improved by lower reaction temperature. The lower temperature is, the more distereoselectivity is upgraded. The calculation demonstrated that all of results are able to be in agreement with experimental data that β-amino acid esters derivatives carrying S as major configuration could arrive to range of 81%~95% ee.

Key words: chiral quinidine, benzothiazol-β-amino esters, DFT, transition state, mechanism