Cooper Lisa, Alonso José Miguel, Eagling Louise, Newson Helen, Herath Sachini, Thomson Christopher, Lister Andrew, Howsham Catherine, Cox Brian, Muñoz María Paz
School of Chemistry, University of East Anglia, Earlham Road, Norwich, NR4 7TJ, UK.
Novartis Pharmaceuticals (UK) Limited, RH12 5AB, Horsham, West Sussex, UK.
Chemistry. 2018 Apr 20;24(23):6105-6114. doi: 10.1002/chem.201705417. Epub 2018 Mar 5.
Optimisation, scope and mechanism of the platinum-catalysed addition of indoles to indolylallenes is reported here to give 2,3'-BIMs with a novel core structure very relevant for pharmaceutical industry. The reaction is modulated by the electronic properties of the substituents on both indoles, with the 2,3'-BIMs favoured when electron donating groups are present. Although simple at first, a complex mechanism has been uncovered that explains the different behaviour of these systems with platinum when compared with other metals (e.g. gold). Detailed labelling studies have shown Pt-catalysed 6-endo-trig cyclisation of the indollylallene as the first step of the reaction and the involvement of two cyclic vinyl-platinum intermediates in equilibrium through a platinum carbene, as the key intermediates of the catalytic cycle towards the second nucleophilic attack and formation of the BIMs.
本文报道了铂催化吲哚与吲哚基丙二烯加成反应的优化、范围和机理,以得到具有对制药行业非常重要的新型核心结构的2,3'-双吲哚甲烷。该反应受两个吲哚上取代基的电子性质调节,当存在供电子基团时有利于生成2,3'-双吲哚甲烷。尽管该反应起初看似简单,但已发现了一个复杂的机理,该机理解释了这些体系与铂反应时与其他金属(如金)相比的不同行为。详细的标记研究表明,吲哚基丙二烯的铂催化6-内型-环化反应是该反应的第一步,并且通过铂卡宾存在两个处于平衡状态的环状乙烯基-铂中间体,作为催化循环中第二次亲核进攻和双吲哚甲烷形成的关键中间体。