Carbolines are a class of nitrogen-containing heterocycles that fall into four isomeric categories. Because of their similarity, their syntheses have great potential to be modular. We have previously described a transition metal-catalyzed cyclotrimerization strategy for the synthesis of beta-carbolines, and can now extended this methodology to the alpha-isomer. Using a cyanamide functional group as the key linchpin in the synthesis, we will describe two parallel strategies for the synthesis of these molecules: a step-wise sequence involving Rh(I)-catalysis and a second strategy involving tandem Pd(0)-catalysis. We will first describe a short five-step synthesis of the cyanamide precursor, which reacts iodoarenes to produce 2-substituted alpha-carbolines.  We will then report the optimization of the reaction conditions for these two methods, including the effects on the isolated yield due to changes in solvent, ligand, temperature, stoichiometry, and reaction length. We will also report a detailed substrate scope that examines the impact on the overall yield of electron-withdrawing or electron-donating substituents on the iodoarene. Key differences and similarities between the efficiencies of the two cyclotrimerization pathways will also be discussed.<br/>

Transition-metal-catalyzed synthesis of 2-substituted alpha-carbolines

2019 Spring National Meeting

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