Direct Use of Benzylic Alcohols for Multicomponent Synthesis of 2‐Aryl Quinazolinones Utilizing the π‐Benzylpalladium(II) System in Water
Hidemasa Hikawa, Taku Nakayama, M. Takahashi, Shoko Kikkawa, Isao Azumaya
Abstract
Abstract We demonstrate the direct use of benzylic alcohols for a multicomponent reaction of readily available isatoic anhydrides with amines in water, which is a synthetic route for the direct construction of a series of 2‐aryl quinazolinones. This one‐pot synthetic method involves the dehydrative N‐benzylation of in situ generated anthranilamides followed by an amide‐directed benzylic C−H amination process utilizing the π‐benzylPd(II) system. Comparison of independent rate measurements using benzyl alcohol and its deuterated form gave a kinetic isotope effect of 3.5. Therefore, the benzylic C−H bond is cleaved in the rate‐determining step. We successfully carried out a gram‐scale reaction in 85% yield with simplified product isolation. magnified image