Oxidative Pd(II)-Catalyzed C-H Bond Activation Route to Carbazoles

Significance

The Pd-catalyzed synthesis of ­substituted carbazoles via direct aromatic C-H activation at ambient temperature is presented. The optimal reaction conditions were identified as Pd(OAc)₂ as catalyst in the presence of PhI(OAc)₂ as a stoichiometric oxidant using toluene as solvent. In several cases, AcOH was used as an additive. Simple alkyl, benzyl and allyl groups on ­nitrogen were all well tolerated, as well as a more complex N-glycoside. The reaction is also amenable to a wide range of groups on both aromatic rings, although electron-rich substrates were found to undergo reaction faster than electron-­deficient analogues. A tandem reaction was also demonstrated whereby 3 was first iodinated at the para-position as expected and the resulting intermediate underwent C-H activation-cyclization in one pot to give 4, allowing for further functionalization through a well-precedented Suzuki cross-coupling reaction.