Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (7): 809-814.DOI: 10.6023/A14040246 Previous Articles     Next Articles

Special Issue: 不对称催化与合成



吕健, 秦岩, 程津培, 罗三中   

  1. 中国科学院化学研究所 北京分子科学国家实验室 分子识别与功能院重点实验室 北京 100190
  • 投稿日期:2014-04-02 发布日期:2014-04-21
  • 通讯作者: 罗三中
  • 基金资助:

    项目受国家自然科学基金(Nos.21025208,21202170,21390400)和973 项目(No.2012CB821600)资助.

Counteranions of In(Ⅲ) Induced Reversal of Enantiocontrol in Friedel-Crafts Reaction of Indoles by Asymmetric Binary Acid Catalysis

LÜ Jian, Qin Yan, Cheng Jinpei, Luo Sanzhong   

  1. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Functions, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100190
  • Received:2014-04-02 Published:2014-04-21
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21025208, 21202170 and 21390400) and the 973 Program (No. 2012CB821600).

Effective access to both enantiomers of any targeted products from a single chiral source of catalyst is highly desirable in asymmetric catalysis. Such dual stereocontrol has normally been encountered with structural modifications on the chiral ligands or catalysts skeletons. Recently, simple variations of reactions conditions such as solvents, temperature, additive and catalytic metal center, can lead to remarkable reversal of enantioselectivity with minimum structural modifications, thus providing a modular and synthetic appealing approach in asymmetric catalysis and synthesis. Previously, we have developed asymmetric binary acid catalysis wherein chiral Brønsted acids, mostly phosphoric acids, are utilized as dual acids and ligands in concert with metal catalysts, and this type of catalysis demonstrated tunable, even switchable stereoselectivity due to the combinatorial and synergistic features. In particular, simple swap of counteranion (from F- to Br-) of Indium(Ⅲ) salts led to complete switch of regioselectivity (1,2- vs. 1,4- addition) in the reaction of N-methyl indole 2a' and ketoester 3a with high enantioselectivity achieved for both regioisomers. In our further studies, we have found that when indole 2a was employed instead of N-methyl indole 2a', the counter anion effect on regioselectivity was not observed and both InF3 and InBr3 promoted exclusively 1,4-addition reactions. Interestingly, reversal of enantioselectivity of the 1,4-conjugate adduct was observed by simple swap of counter anions of indium(Ⅲ). The obtained optimal binary-acids combination, InF3(1c)2 and InBr3(1d)2 were found to be R- and S-selective catalyst for the 1,4-addition reactions, respectively. In the presence of asymmetric binary-acid catalysts (InX3/1, 2.5 mol%), indoles and β,γ-unsaturated α-ketoesters were stirred at -70 ℃ for 24 h to afford the various indole esters 4 in good to excellent yield (up to 98% yield ) and enantioselectivities (up to>99% ee).

Key words: asymmetric catalysis, Friedel-Crafts alkylation, switchable enantioselectivity, binary-acid, counter anion effect