Photo-Induced Pyridylic C(sp³)-H Alkylation with Unactivated Alkenes Enabled by Hydrogen Atom Transfer/Lewis Acid Cocatalysis

Radical hydroalkylation of alkenes represents an ideal approach for C(sp³)-C(sp³) bond formation. However, radical precursors have been substantially limited due to the sluggish nature of less electrophilic carbon-centered radicals to participate in addition step toward unactivated alkenes. Herein, we demonstrate that this inherent limitation can be overcome by the use of a Lewis acid catalyst. This cocatalytic system enables the hitherto elusive radical C(sp³)-C(sp³) bond formation between pyridylacetates and unactivated alkenes to generate medically relevant valuable products. Computational studies support that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate-determining radical addition step.