Pd-Catalyzed Dearomative Functionalizations of Benzyl and Aryl Electrophiles

Dearomative functionalization is a powerful method to construct structurally complex alicyclic frameworks from simple and abundant aromatic molecules. Although a myriad of dearomative functionalizations have been reported so far, the reaction of electron-neutral arenes such as benzenes and naphthalenes are a still challenging issue due to their high aromatic stability, often requiring an excess amount of aromatic starting materials. Recently, we have developed catalytic dearomative functionalization of electron-neutral arenes by focusing on the unique reactivity of π-benzyl palladium catalysis. In this manuscript, we describe our endeavor to develop the dearomative C-C bond formations of benzyl alcohol derivatives, benzyl ammoniums, and bromoarenes. The dearomatized compound was transformed into various alicyclic skeletons by diverse derivatizations. Furthermore, we successfully achieved dearomative C-N bond formation with bromo(hetero)arenes, resulting in the synthesis of azaspirocycles. Utilizing the present methodology, the total synthesis of Cephalotaxus alkaloids with a unique complex polycyclic skeleton, has also been accomplished.