Synthesis of a Novel Type of 2,3′‐BIMs via Platinum‐Catalysed Reaction of Indolylallenes with Indoles

• Published in: Chemistry : a European journal Vol. 24; no. 23; pp. 6105 - 6114
• Main Authors: Cooper, Lisa, Alonso, José Miguel, Eagling, Louise, Newson, Helen, Herath, Sachini, Thomson, Christopher, Lister, Andrew, Howsham, Catherine, Cox, Brian, Muñoz, María Paz
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 20.04.2018; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: allenes; Catalysis; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Gold; Heavy metals; heterocycles; Indoles; Intermediates; Labeling; Pharmaceutical industry; Physical Sciences; Platinum; reaction mechanisms; Science & Technology; CONVENIENT SYNTHESIS; OXYGEN NUCLEOPHILES; GOLD CATALYSIS; EXPEDIENT SYNTHESIS; reaction mechanisms; allenes; indoles; platinum; heterocycles; ANTIBACTERIAL ACTIVITY; REGIOSELECTIVE SYNTHESIS; GENERAL-APPROACH; H BONDS; C TRIPLE BONDS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201705417

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. Closing up: Unique reactivity of indolylallenes under platinum catalysis to form substituted tetrahydropyrido[1,2a]indoles: an original type of 2,3′‐BIM.