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

Abstract

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.

Heterobimetallic Catalysis: Platinum‐Gold‐Catalyzed Tandem Cyclization/C−X Coupling Reaction of (Hetero)Arylallenes with Nucleophiles

“…Taking into account all the experimental evidence, we propose a fast homogeneous Au‐catalyzed 6‐ endo‐trig carbocyclization of the heteroarylallenes to furnish, after protodemetallation, 3 a , the first reaction intermediate observed in the process (Scheme , cycle 1). The intermediate 3 a would then enter into the second catalytic cycle (Scheme , cycle 2), promoted by [Pt‐AuPPh 3 ] homogeneous clusters and aided by Pt‐Au particles in the heterogeneous phase, with the heterobimetallic carbene E as the key intermediate.…”

“…Previous studies have shown that Pt is able to promote the 6‐ endo ‐ trig carbocyclization in 1 a , and that 3 and 3′ are true intermediates of the reaction, with Pt‐catalyzed isomerization of 3 to 3′ occurring before the intermolecular nucleophilic addition . Nevertheless, PtCl 2 is not able to promote the carbocyclization of the allenes 1 b – d in an efficient manner under our reaction conditions .…”

When Indoles Meet Allene and its Derivatives

“…In a different approach, Muñoz & Alonso reported the first tandem process for the platinum catalyzed carbocyclization/nucleophilic addition of N ‐indolylallenes 140 with indoles, accessing the challenging 2,3'‐bisindolylmethane skeleton 141 (Scheme 31a). [ 73 ] This methodology takes one step forward the gold‐catalyzed cyclization of N ‐indolylallenes, that is not able to undergo the intermolecular nucleophilic addition. However, first investigations showed poor conversions and scope limitations with products 142a and 142b (like 96 obtained under gold catalysis, see Scheme 23) obtained as major or only products when deactivated indoles were used.…”

Recent Advance on the Synthesis of 3,3'-Bisindolylmethane Derivatives under Transition-Metal-Free Catalytic Conditions

“…In addition, the generation of the stoichiometric chemical and metallic wastes could cause serious environmental issues, which was not suitable with the development of modern sustainable chemistry. [25][26][27][28][29][30][31][32][33] Bisindolylmethanes (BIMs) and trisindolylmethanes (TIMs) were well reviewed by Shiri et al [34] in 2010, in which they summarized the various approaches to BIMs and TIMs, including 3,3'-BIMs, 2,2'-BIMs, 2,3'-BIMs and TIMs.…”