Catalytic Dehydrative Benzylation Using Benzyl Alcohols in Water

We developed a Pd(0)/TPPMS-catalyzed benzylation of a variety of nucleophiles using benzyl alcohols in water. In the first section of this account, we demonstrate that π-benzylpalladium species enable an N-benzylation/benzylic C-H benzylation cascade applicable to a wide range of aromatic amines, affording the corresponding dibenzylated products. The initially formed N-benzylated intermediates can react with π-benzylpalladium complexes to generate bis(π-benzyl)palladium intermediates. In this process, the nucleophilic η1-σ-benzyl ligand attacks the electrophilic η3-π-benzyl ligand to form a new benzylic C-C bond. In the second section, we apply this catalytic system to the N-benzylation reaction via the borrowing hydrogen methodology. Because electron-deficient nucleophiles such as 2-aminopyridines are unreactive toward the electrophilic π-benzylpalladium intermediate, Tsuji-Trost-type benzylation does not proceed. Instead, the palladium species reacts with benzyl alcohol, initiating a borrowing hydrogen process through dehydrogenation. In the third section, we demonstrate the direct use of benzylic alcohols in a multicomponent reaction of isatoic anhydrides with amines in water, providing an efficient synthetic route to a series of 2-arylquinazolinones.