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

Abstract

An N‐heterocyclic carbene catalyzed benzylic Csp³–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.