Mechanism and Origins of Site-Selectivity of Template-Directed C-H Insertion of Quinolines

The template-directed C-H insertion of alpha,beta-unsaturated esters into quinoline was interrogated by using computational quantum chemistry. An energetically viable mechanism for this complex multistep transformation was elucidated, with attention paid throughout to conformational flexibility and alternative ligand binding modes. The selectivity was found to correlate with distortion from a tetrahedral geometry for the carbon atom involved in C-H insertion, a parameter that can be applied to future template design.

Automated summary

The template-directed C-H insertion of alpha,beta-unsaturated esters into quinoline was studied using computational quantum chemistry. A feasible mechanism for this complex transformation was elucidated, taking into account conformational flexibility and alternative ligand binding modes. The selectivity was found to be correlated with distortion from a tetrahedral geometry, which can guide future template design.