Catalytic, Regioselective Hydrocarbofunctionalization of Unactivated Alkenes with Diverse C–H Nucleophiles

Reactions
that forge carbon–carbon (C–C) bonds are
the bedrock of organic synthesis, widely used across the chemical
sciences. We report a transformation that enables C–C bonds
to be constructed from two classes of commonly available starting
materials, alkenes and carbon–hydrogen (C–H) bonds.
The reaction employs a palladium­(II) catalyst and utilizes a removable
directing group to both control the regioselectivity of carbopalladation
and enable subsequent protodepalladation. A wide range of alkenes
and C–H nucleophiles, including 1,3-dicarbonyls, aryl carbonyls,
and electron-rich aromatics, are viable reaction partners, allowing
Michael-type reactivity to be expanded beyond α,β-unsaturated
carbonyl compounds to unactivated alkenes. Applications of this transformation in drug
diversification and natural product total synthesis are described.
Stoichiometric studies support each of the proposed steps in the catalytic
cycle.