Chiral nitrogen-containing heterocycles continue to present opportunities for new asymmetric synthetic methodology. We previously introduced a manganese-mediated radical-ionic annulation pathway for construction of pyrrolidines by addition of 3-chloropropyl iodide to chiral N-acylhydrazones. Radical addition is followed by an SN2-type cyclization. Now we report related radical-polar crossover reactions in which the leaving group is present in the hydrazone radical acceptor, providing access to 2-alkylpyrrolidines and 2-alkylpiperidines depending on proximity between nucleophile and leaving group. Various iodides, including primary iodides, are used as radical precursors, and the reactions are achieved with excellent stereocontrol to afford common substructures of many biologically active natural products.

Mn-mediated radical-polar crossover annulation employing a leaving group in the N-acylhydrazone radical acceptor

249th National Meeting (2015)

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