Palladium-catalyzed aerobic alpha,beta-dehydrogenation of carbonyl compounds: Method development and mechanistic study

α,β-Unsaturated carbonyl compounds are versatile intermediates in the synthesis of pharmaceuticals and biologically active molecules. The research described herein focuses on the development and mechanistic study of Palladium catalysts for direct aerobic dehydrogenation of ketones and aldehydes to afford the corresponding α,β-unsaturated carbonyl compounds. The discovery and application of a novel aerobic dehydrogenation catalyst, Pd(DMSO)2(TFA)2, led to selective dehydrogenation of various cyclohexanone derivatives to afford cyclohexenone products that are of synthetic interest. A complementary Pd(TFA)2/4,5-diazafluorenone catalyst was developed for α,β-dehydrogenation of acyclic ketones and aldehydes, with useful applications in preparing unsaturated heterocyclic carbonyl compounds. Characterization of the solution-phase structure of the Pd(DMSO)2(TFA)2 catalyst by NMR spectroscopy suggested that the bis-DMSO ligation to PdII was favorable under the catalytic conditions. Further kinetic studies of Pd(DMSO)2 (TFA)2-catalyzed dehydrogenation of cyclohexenone revealed that the DMSO ligands kinetically control the selectivity of dehydrogenation.;A fundamental study of the influence of O2 on the acetoxylation of (π-allyl)Pd complexes is also detailed. The fact that O2 is capable of promoting reductive C-O bond formation of (π-allyl)Pd complexes has important implications in understanding the interaction between Pd and O2 and provides a basis for development of Pd-catalyzed aerobic allylic acetoxylation of alkenes.