Asymmetric methods for the synthesis of atropisomeric β-carbolines | Poster Board #1712

Atropisomerism is a form of dynamic chirality that is most commonly observed in biaryl systems. This form of chirality has been harnessed in drug discovery and chemical biology for the design of functional molecules with great success. Our group has shown that β-carbolines substituted with an aryl group at the 1-position exhibit atropisomerism with barriers to rotation greater than 30 kcal/mol. We now report initial results on the asymmetric synthesis of these molecules. Our strategy makes use of a six-step synthesis of a diyne precursor which undergoes a rhodium-catalyzed [2+2+2] cyclotrimerization reaction with an exogenous nitrile to form both the β-carboline and the atropisomeric axis in the process. We will describe our optimization of this reaction with respect to concentration, solvent, and stoichiometry, as well as report our initial results at asymmetric induction using a chiral ligand.