Quaternary Carbons from Amines and Acids

C-C coupling method that uses amines and carboxylic acids, which are among the most broadly available building blocks in vendor catalogs. Our method achieves the coupling of tertiary carbon centers to access dense carbon architectures including from complex pharmaceutical and natural product substrates. Preactivation of both the amine and acid functional groups enables an iron catalyst to unite the carbon-based building blocks under reducing conditions, which were identified using high-throughput experimentation. Extensive electron paramagnetic resonance measurements highlight the intermediacy of radicals and the spin state transformation of iron during the reaction. Our amine-acid coupling establishes a method for navigating chemical space that complements the current toolbox of carbon-carbon bond-forming reactions.