On the mechanism of the Au(I)-mediated addition of alkynes to anthranils to furnish 7-acylindoles

Indole is a very common structural motif in alkaloids with a remarkable history in pharma industry. In the continuous search for more direct and efficient access to these valuable structures, a new and rather elegant approach was found by Jin and coworkers, which involved a gold(I)-mediated addition of alkynes onto anthralins. This approach selectively furnishes 7-acylindoles in a rather expeditious way, and it has been shown to be compatible with a large range of decorated reactants, both at the alkyne side and at the anthralin side. We studied the mechanism of this reaction with a set of different alkynes, including disubstituted ones, to establish similarities and differences between them and to aid in the elucidation of key steps in the reaction pathway. The observed regioselectivity seems to be connected to the irreversible formation of a key alpha-imino gold carbene intermediate, common to all reaction profiles, through the initial regioselective nucleophilic attack of the anthranil N atom onto the alkyne fragment.

Automated summary

Indole is a common structural motif in alkaloids and has significant importance in the pharmaceutical industry. A new and elegant approach using gold(I) as a catalyst has been discovered to efficiently synthesize 7-acylindoles, and it is compatible with a wide range of reactants. The mechanism study reveals that the regioselectivity is related to the formation of an α-imino gold carbene intermediate.