Metal-Free Synthesis of Highly Substituted Pyridines by Formal [2+2+2] Cycloaddition under Mild Conditions

The synthesis of pyridines through direct intermolecular cycloaddition of alkynes and nitriles is a contemporary challenge in organic synthesis. A Brønsted acid mediated formal [2+2+2] cycloaddition of heteroalkynes and nitriles was developed that proceeds under mild conditions. This constitutes a modular approach to highly substituted pyridine cores. When 2+2+2=π: The synthesis of pyridines through direct intermolecular cycloaddition of alkynes and nitriles is a contemporary challenge in organic synthesis. A Brønsted acid mediated formal [2+2+2] cycloaddition of heteroalkynes and nitriles was developed that proceeds under mild conditions. This constitutes a modular approach to highly substituted, densely functionalized pyridine cores.