Cross-Dehydrogenative Coupling of Heterocyclic Scaffolds with Unfunctionalized Aroyl Surrogates by Palladium(II) Catalyzed C(sp²)‑H Aroylation through Organocatalytic Dioxygen Activation

Abstract

Cross-dehydrogenative coupling of biorelevant heterocyclic scaffolds with arylmethanes for aroylation during Pd­(II)-catalyzed C­(sp²)-H activation has been achieved through dioxygen activation by NHPI. Mass spectrometry and ¹H NMR based kinetic isotope effect studies revealed C–H bond activation as the rate-determining step. Radical scavenging experiments indicated a radical pathway. The ¹H NMR of an aliquot of reaction mixture and in situ trapping with 2-aminothiophenol revealed the formation of aldehyde during aerobic oxidation of the arylmethanes. The reaction has broad scope for different variations of the aroyl source and the directing group that includes benzothiazole, benzooxazole, pyridine, quinoxaline, pyrimidine, and azoarene. The benzylic methylene moiety was found to be the source of the aroyl carbon with the benzyl ether moiety being the most preferred followed by the carbonyl group of aryl aldehyde and the aryl methane. However, the ease of availability of aryl methanes makes them the most attractive as an aroyl source. A time dependent selective mono- and bis-aroylation can be achieved. The 1,3-diarylpyrimidines exhibited regioselective aroylation of the 2-phenyl moiety irrespective of the absence or presence of any substitutent (electron withdrawing or electron donating) in the 3-phenyl moiety. For unsymmetrical azoarenes, selective aroylation took place in the phenyl moiety bearing the substituent