[Co(TPP)]-Catalyzed Formation of Substituted Piperidines

Radical cyclization via cobalt(III)–carbene radical intermediates is a powerful method for the synthesis of (hetero)cycles. Building on the recently reported synthesis of N-heterocyclic pyrrolidines catalyzed by Co(II) porphyrins, we herein report the [Co(TPP)]-catalyzed formation of desirable six membered N heterocyclic piperidines, directly from linear aldehydes. Piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)-porphyrin-catalyzed formation of pyrrolidines, piperidines and linear alkenes. The calculations show that the alkenes are unlikely to be formed through 1,2-HAT. Instead, the calculations are consistent with a pathway involving benzyl radical formation followed by radical rebound ring-closure to form the piperidines. Competitive 1,5-HAT from the beta-position to the benzyl radical explains the formation of linear alkenes.