The interplay of polar effects in controlling the selectivity of radical reactions

Radical reactivity is a powerful tool for molecular construction that often provides bond-forming strategies and retrosynthetic disconnections complementary to those available through ionic and metal-mediated approaches. Understanding reactivity and selectivity patterns in radical chemistry is crucial to harness and develop the full potential of open-shell species in synthetic settings. Polar effects operate at the transition-state level of all radical reactions and have important implications in controlling their outcomes. The recognition of the key factors that respond to polar effects can be used to understand reactivity trends and also to rationally enhance (or mute) the intrinsic reactivity of specific molecular sites over others. These features render radical reactivity easy to predict and, therefore, programmable. In this Review we highlight some of the key underlining mechanistic features associated with polar effects and we accompany our discussion with representative synthetic examples. Polar effects permeate radical chemistry and control the outcome of radical reactions. This Review discusses important types of polar effects and how their interplay has been used in the synthesis and late-stage modification of complex molecules. The discussion covers hydrogen-atom transfer, halogen-atom transfer and homolytic aromatic substitution.