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-1H-pyrido[4,3-b]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.