Enabling reactivity of neutral aminyl radicals in polycyclic heterocycle synthesis

Tertiary aliphatic amines are a privileged functional group in pharmaceuticals. For example, 51% of FDA approved nervous system drugs possess a tertiary aliphatic amine. However, there is only one neurologic agent with this functionality disposed at a ring junction. This imbalanced representation of structural space likely points to a need for more efficient strategies for the synthesis of these compounds, rather than an inherent problem with these structures as drug agents. We have devised a general strategy to potentially access a variety of such compounds using radical cascade reactions of N-centered radicals. In this seminar, a successful example of our approach that employs neutral dialkyl aminyl radicals will be discussed in the context of our efforts toward the total syntheses of the plant alkaloids daphniyunnine C and daphnicyclidin A.