Efficient and Scalable Synthesis of 3,4-Dihydroisoquinolin-1(2H)-ones by Benzylic Oxidation of Tetrahydroisoquinoline Derivatives using Cerium Ammonium Nitrate (CAN)

An efficient and scalable method for the synthesis of 3,4-dihydroisoquinolin-1(2H)-ones through benzylic oxidation of tetrahydroisoquinoline derivatives using a catalytic amount of cerium ammonium nitrate (CAN) and a stoichiometric amount of NaBrO3 as oxidants was developed. The reaction is significantly influenced by the substituent groups on the phenyl ring. While electron-withdrawing groups on the phenyl ring can lower the reactivities of the substrates, electron-donating groups on the phenyl ring can dramatically promote the oxidation rate.