meso-2,3-dibromosuccinic acid as a temperature-dependent catalyst for the selective synthesis of syn and anti-highly functionalized tetrahydropyridines: experimental and theoretical study.

This study reports the flexible synthesis of syn-anti isomers of highly functionalized tetrahydropyridines under controlled temperature conditions. The present catalytic system employs cost-effective meso-2,3-dibromosuccinic acid in a one-pot, multicomponent process involving both aromatic aldehydes, anilines, and 1,3-dicarbonyl compounds to produce a structurally diverse tetrahydropyridines. The current catalyst, meso-2,3-dibromosuccinic acid, demonstrates a unique capability for selective synthesis of syn:anti tetrahydropyridine isomers. Unlike other reported catalysts, it enables exclusive formation of the syn isomer at low temperatures (5 °C) and allows tunable syn:anti ratios at moderate temperatures (25 °C). Moreover, at 65 °C, meso-2,3-dibromosuccinic acid exclusively yields the anti isomer highlighting its distinct advantage in controlling product selectivity. Other notable features of this method include simple work-up procedure, the absence of transition metal catalysts, high structural diversity of the products, and excellent product yields. Thermodynamics, kinetics, aromaticity, frontier orbitals, and