Ethynyl Benziodoxolones for the Direct Alkynylation of Heterocycles: Structural Requirement, Improved Procedure for Pyrroles, and Insights into the Mechanism
Ethynyl Benziodoxolones for the Direct Alkynylation of Heterocycles: Structural Requirement, Improved Procedure for Pyrroles, and Insights into the Mechanism
复制标题
DOI：
10.1002/chem.201200200
复制
发表时间：
2012-04-01
影响因子：
4.3
通讯作者：
Waser, Jerome
中科院分区：
文献类型：
--
作者：
Brand, Jonathan P.;Chevalley, Clara;Waser, Jerome
本报告描述了用炔基高价碘试剂对金催化的吲哚、吡咯和噻吩的直接炔基化反应的全面研究，特别是炔基苯并碘唑酮对乙炔有效转移到杂环的结构要求的研究。本文还报道了一种以吡啶为添加剂的吡咯烷化反应的改进方法。合成了19个炔基苯并碘多酚，并对吲哚和/或噻吩的直接炔基化反应进行了评价。体积较大的硅基作为乙炔取代基是最理想的。然而，首次实现了芳香族乙炔向噻吩的转移。在三异丙基硅乙基-1,2-苯并多酚-3(1H)- 1 （TIPS-EBX）的3位和6位上加入一个甲基取代基对反应速率有加速作用。不同亲核性底物之间的竞争实验、氘标记实验以及所观察到的区域选择性都与亲电芳香取代一致。二氯化金（III） 2-吡啶甲酸酯也是该反应的有效催化剂。研究表明，在此过程中，金（III）最终可以还原为金(I)。这些研究的结果表明，p活化或氧化机制是最可能的烷基化反应。
This report describes a full study of the gold-catalyzed direct alkynylation of indoles, pyrroles, and thiophenes using alkynyl hypervalent iodine reagents, especially the study of the structural requirements of alkynyl benziodoxolones for an efficient acetylene transfer to heterocycles. An improved procedure for the alkynylation of pyrroles using pyridine as additive is also reported. Nineteen alkynyl benziodoxol(on)es were synthesized and evaluated in the direct alkynylation of indoles and/or thiophenes. Bulky silyl groups as acetylene substituents were optimal. Nevertheless, transfer of aromatic acetylenes to thiophene was achieved for the first time. An accelerating effect of a methyl substituent in both the 3- and 6-position of triisopropylsilylethynyl-1,2-benziodoxol-3(1H)-one (TIPS-EBX) on the reaction rate was observed. Competitive experiments between substrates of different nucleophilicity, deuterium labeling experiments, as well as the regioselectivity observed are all in agreement with electrophilic aromatic substitution. Gold(III) 2-pyridinecarboxylate dichloride was also an efficient catalyst for the reaction. Investigations indicated that gold(III) could be eventually reduced to gold(I) during the process. As a result of these investigations, a p activation or an oxidative mechanism are most probable for the alkynylation reaction.