From 3-Acyl-2-methylindoles to γ-Carbolines: Li-Promoted Cycloaddition Reaction and Its Quantum Chemical Study.

A one-pot cycloaddition strategy for obtaining γ-carbolines under mild conditions was developed. The reaction represents a new approach to the annulation of a pyridine ring to an indole core. Treating 2-methyl-3-benzoylindoles with lithium diisopropyl amide leads to the elimination of a proton from the 2-methyl group. The organolithium compounds generated were found to react with nitriles. The resulting 4,5-dihydro-1-pyrido[4,3-]indol-1-ols undergo spontaneous water elimination to give the corresponding γ-carbolines. The applicability of this reaction for the synthesis of isoquinolines has been shown. For the first time, a lithium atom was found to be part of an eight-centered polycyclic transition state according to a detailed DFT PCM/DFT/B3LYP/6-311++G(d,p) and ab initio PCM/MP2//HF/6-311++G(d,p) quantum chemical study.