Engaging Diastereomeric syn- and anti-6-Bromo-4a-isopropyl-2-methyl-2,3,4,4a-tetrahydro-1H-carbazoles in Suzuki Coupling Reaction: Synthesis, Spectral Characterization and DFT Studies

Suzuki coupling reaction is one of the useful methods for carbon-carbon bond formation. In the present study, the aforementioned method is used to expand an aryl appendage on the indolenine nucleus of diastereomeric syn- and anti-6-bromo-4a-isopropyl-2-methyl-2,3,4,4a-tetrahydro-1H-carbazole analogs. Therefore, two sets of new diastereomeric Suzuki-coupled products (16 compounds) were prepared. For this, diastereomeric syn- and anti-6-bromo-4a-isopropyl-2-methyl-2,3,4,4a-tetrahydro-1H-carbazole analogs were treated with arylboronic acids in the presence of palladium catalyst under thermal catalysis. Structures of synthesized compounds were inferred using spectroscopic studies. DFT-based quantum chemical calculations were used to decipher structural attributes and stability of diastereomeric bromo-2,3,4,4a-tetrahydro-1H-carbazoles and their Suzuki-coupled products, which revealed chair conformation for methylcyclohexane ring of syn-compound while twist-boat conformation for diastereomeric anti-compound. syn-Compound was found more stable than its anti-isomer based on DFT-calculations. Also, results demonstrated agreement between experimental and theoretical chemical shift values in NMR spectra with some deviations. Thus, structural elucidation based on computational advances in combination with the spectroscopic method can provide a powerful method for studying and comparing the structural attributes of diastereomeric compounds.