Decarboxylative Addition of Propiolic Acids with Indoles to Synthesize Bis(indolyl)methane Derivatives with a Pd(II)/LA Catalyst

Exploring new protocols for efficient organic synthesis is crucial for pharmaceutical developments. The present work introduces a Pd­(II)/LA-catalyzed (LA: Lewis acid) decarboxylative addition reaction for the synthesis of bis­(indolyl)­methane derivatives. The presence of Lewis acid such as Sc­(OTf)3 triggered Pd­(II)-catalyzed decarboxylative addition of propiolic acids with indoles to offer the bis­(indolyl)­methane derivatives in moderate to good yields, whereas neither Pd­(II) nor Lewis acid alone was active for this synthesis. The catalytic efficiency of Pd­(OAc)2 was highly dependent on the Lewis acidity of the added Lewis acid, that is, a stronger Lewis acid provided a higher yield of the bis­(indolyl)­methane derivatives. Meanwhile, this Pd­(II)/LA-catalyzed decarboxylative addition reaction showed good tolerance toward versatile electron-rich or -deficient substituents on the indole skeleton and on the benzyl ring of propiolic acids. The studies on the in situ 1H NMR kinetics of this Pd­(II)/Sc­(III) catalysis disclosed the formation of a transient vinyl-Pd­(II)/Sc­(III) intermediate generated by the pyrrole addition to the alkynyl-Pd­(II)/Sc­(III) species after decarboxylation, which was scarcely observed before.