Practical One‐Pot Multistep Synthesis of 2H‐1,3‐Benzoxazines Using Copper, Hydrogen Peroxide, and Triethylamine.

In this article, we describe simple one‐pot syntheses of 2H‐1,3‐benzoxazines from ketones utilizing an imino‐pyridine directing group (R1R2‐C=N−CH2‐Pyr), which promotes a Cu‐directed sp2 hydroxylation using H2O2 as oxidant and followed by an oxidative intramolecular C−O bond formation upon addition of NEt3. This synthetic protocol is utilized in the gram scale synthesis of the 2H‐1,3‐benzoxazine derived from benzophenone. Mechanistic studies reveal that the cyclization occurs via deprotonation of the benzylic position of the directing group to produce a 2‐azallyl anion intermediate, which is oxidized to the corresponding 2‐azaallyl radical before the C−O bond formation event. Understanding of the cyclization mechanism also allowed us to develop reaction conditions that utilize catalytic amounts of Cu. [ABSTRACT FROM AUTHOR]