Modular Synthesis of Benzocyclobutenes via Pd(II)-Catalyzed Oxidative [2+2] Annulation of Arylboronic Acids with Alkenes

Benzocyclobutenes (BCBs) are highly valuable compounds in organic synthesis, medicinal chemistry, and materialsscience. However, catalytic modular synthesis of functionalized BCBs from easily accessible starting materials remains limited. Wereport herein an efficient synthesis of diversely functionalized BCBs by a Pd(II)-catalyzed formal [2+2] annulation betweenarylboronic acids and alkenes in the presence ofN-fluorobenzenesulfonimide (NFSI). An intermolecular carbopalladation followedby palladium oxidation, intramolecular C(sp2)-H activation by a transient C(sp3)-Pd(IV) species, and selective carbon-carbon(C-C) bond-forming reductive elimination from a high-valentfive-membered palladacycle is proposed to account for the reactionoutcome. Kinetically competent oxidation of alkylPd(II) to alkylPd(IV) species is important to avoid the formation of a Heckadduct. The reaction forges two C-C bonds of the cyclobutene core and is compatible with a wide range of functional groups. Nochelating bidentate directing group in the alkene part is needed for this transformation

Automated summary

In this study, an efficient synthesis of diversely functionalized benzocyclobutenes (BCBs) was reported. The synthesis was achieved through a Pd(II)-catalyzed formal [2+2] annulation between arylboronic acids and alkenes in the presence of N-fluorobenzenesulfonimide (NFSI). The reaction mechanism was also proposed.