Synthesis of Cyclic Enones via Direct Palladium-Catalyzed Aerobic Dehydrogenation of Ketones

Abstract

α,β-Unsaturated carbonyl compounds are versatile intermediates in the synthesis of pharmaceuticals and biologically active compounds. Here, we report the discovery and application of Pd(DMSO)2(TFA)2 as a catalyst for direct dehydrogenation of cyclohexanones and other cyclic ketones to the corresponding enones, using O2 as the oxidant. The substrate scope includes heterocyclic ketones and several natural-product precursors.

Aerobic Dehydrogenation of Cyclohexanone to Phenol Catalyzed by Pd(TFA)2/2-Dimethylaminopyridine: Evidence for the Role of Pd Nanoparticles

“…This reactivity bridges the gap between the homogeneous and heterogeneous catalytic dehydrogenation reactions. Pd(DMSO) 2 (TFA) 2 mediates selective dehydrogenation of cyclohexanones to cyclohexenones, 6 and mechanistic studies supported the involvement of a homogeneous catalyst. 7 Heterogeneous Pd catalysts, such as Pd/C, promote dehydrogenation of cyclohexenones to phenols under forcing conditions (e.g., 200 °C), 2a–d,3i but such catalysts are not active under the mild conditions used for the present reactions (cf.…”

Palladium-Catalyzed Aerobic Dehydrogenation of Cyclic Hydrocarbons for the Synthesis of Substituted Aromatics and Other Unsaturated Products

“…The time course data were fit to a simple A→B→C kinetic model in order to compare the relative rates of the two steps with the two different catalyst systems. 22 With the Pd(TFA) 2 /2-NMe 2 py catalyst, the first step is almost two-fold slower than the second step ( k 1 / k 2 = 0.61). The reaction also exhibited a significant non-zero concentration of cyclohexenone, however, arising from a kinetic burst of enone formation (see further discussion below).…”

“…A Pd(TFA) 2 /DMSO (1:2) catalyst system was identified that enabled efficient and chemoselective access to the monodehydrogenation products with O 2 as the sole oxidant. 22 Key differences between the phenol formation catalyst and the newly developed catalyst are the use of DMSO as a catalytic ligand, rather than a solvent, and the use of AcOH, EtOAc or toluene as solvent. 4-Substituted cyclohexanones, N -substituted piperidones, chromanones, as well as 5- and 7-membered cyclic ketones were smoothly converted to the α,β-unsaturated products (Scheme 13A).…”

Aerobic Dehydrogenation of Cyclohexanone to Cyclohexenone Catalyzed by Pd(DMSO)2(TFA)2: Evidence for Ligand-Controlled Chemoselectivity

“…9, 10 Finally, a Pd(DMSO) 2 (TFA) 2 catalyst enables selective dehydrogenation of cyclohexanones to cyclohexenones. 11 The reactions mediated by these catalysts provide compelling routes to substituted phenols and/or enones, and they serve as an important foundation for the development of other aerobic dehydrogenation methods. A number of related transformations, including reactions for the synthesis of aryl ethers and anilines from cyclohexanones and cyclohexenones, have been reported by other groups over the past year.…”