Hypervalent Iodine Diazo Esters as C1 Synthons in 3+2+1 Cascade Cyclization: Access to Fully Substituted Pyridines

Fully substituted pyridines are important cores in natural products, functional materials, and pharmaceuticals. Building such a motif usually requires multiple steps, a transition metal as a catalyst, and external additives. Herein, a 3+2+1 cascade annulation has been developed to synthesize fully substituted pyridines. Hypervalent iodine diazo reagents as highly reactive C1 synthons react with enaminones, leading to a series of fully substituted pyridines in up to 85% yields for 28 examples under catalyst- and additive-free conditions at room temperature. This protocol features easily available substrates and is simple in operation. The versatility of the protocol was showcased by carrying out scale-up synthesis and late-stage transformation of the products.