NHC-Catalyzed Benzylic Csp3-H Bond Activation of Alkylarenes and N-Benzylamines for the Synthesis of 3H-Quinazolin-4-ones: Experimental and Theoretical Study

An N-heterocyclic carbene catalyzed benzylic C-sp(3)-H bond activation of alkylarenes and N-benzylamines under metal-free conditions was developed. This organocatalyzed oxidative transformation afforded the corresponding carbonyl derivatives in good to excellent yields. A variety of alkylarenes and N-benzylamines were tolerated under the optimized reaction conditions. The established method was further extended to the synthesis of biologically important 3H-quinazolin-4-ones in good yields. For example, NPS 53574, a potent calcium receptor antagonist, was successfully synthesized by using this oxidative protocol. DFT studies show that the benzylic C-H bond activation proceeds through the nucleophilic attack of the free carbene on the benzylic carbon atom.