Frame-shifted synthesis of oligoheterocycles as a platform for sustainable molecular design

Chemists need to develop reliable strategies that leverage abundant feedstocks to speed up the production of vital medicines, agrochemicals, and materials. Oligoheterocyclic compounds are one class of molecules that span each of these disciplines. Cross-coupling strategies are commonly used to assemble oligoheterocycles; however, these transformations can be challenging and often rely on costly precious metal catalysts and building blocks derived from unsustainable feedstocks and supply chains. Here, we present a synthetic strategy for iterative construction of oligoheterocycles that leverages sustainable building blocks designed around carbon atoms of high oxidation states. By utilizing feedstocks from the base of the chemical supply chain, we generate bifunctional building blocks that chemoselectively engage with a variety of reaction partners through simple condensation manifolds. Adopting this approach has led to novel scaffolds previously inaccessible by conventional means, which exemplifies sustainable design strategies and enables democratization of chemical synthesis.