Toward the ABCD Core of the Calyciphylline A-Type Daphniphyllum Alkaloids: Solvent non-Innocence in Neutral Aminyl Radical Cyclizations.

The Daphniphyllum alkaloids remain an attractive target in the synthetic community because of their unique framework and promising biological activities. We have shown that the ABC core of the calyciphylline A-type alkaloids can be rapidly accessed via the tandem cyclization of a neutral aminyl radical with a polarized cyclic olefin. Deuterium labeling experiments and reactions omitting a tin hydride reagent suggest that the solvent is the major source of the terminating hydrogen atom in the cyclization cascade. Incorporation of an internal alkyne in the radical pathway was tolerated in the reaction, and it provided the necessary atoms to enable completion of the D ring of the calyciphylline A-type alkaloids.