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

Abstract

The dehydrogenation of cyclohexanones affords cyclohexenones or phenols via removal of one or two equivalents of H2, respectively. We recently reported several PdII catalyst systems that effect aerobic dehydrogenation of cyclohexanones with different product selectivities. Pd(DMSO)2(TFA)2 is unique in its high chemoselectivity for the conversion of cyclohexanones to cyclohexenones, without promoting subsequent dehydrogenation of cyclohexenones to phenols. Kinetic and mechanistic studies of these reactions reveal the key role of the dimethylsulfoxide (DMSO) ligand in controlling this chemoselectivity. DMSO has minimal kinetic influence on the rate of Pd(TFA)2-catalyzed dehydrogenation of cyclohexanone to cyclohexenone, while it strongly inhibits the second dehydrogenation step, conversion of cyclohexenone to phenol. These contrasting kinetic effects of DMSO provide the basis for chemoselective formation cyclohexenones.

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

“…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. Table 1).…”

“…We recently investigated the mechanism of the Pd(DMSO) 2 (TFA) 2 -catalyzed oxidative dehydrogenation of cyclohexanone, 7 and the results support a catalytic cycle in which cyclohexanone undergoes reversible coordination to Pd II , followed by turnover-limiting cleavage of the α-C–H bond (Scheme 2). The resulting PdII-enolate intermediate undergoes rapid β–H elimination to afford the cyclohexenone product and a Pd II -hydride.…”

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

“…For example, our results show that homogeneous and nanoparticle catalysts show different selectivity for the conversion of cyclohexanones to cyclohexenones versus phenols. 28,29 The work of Lemaire, 16,46 together with non-oxidative catalytic applications by Liu and Li, 64 demonstrates the utility of heterogeneous Pd catalysts in related applications. The development of new catalyst systems in future studies will undoubtedly play an important role in continued expansion of this field.…”

“…28 The cyclohexanone-to-cyclohexenone step exhibited only minor rate dependence on DMSO (Scheme 16A); however, high product yield was obtained only in the presence of DMSO. Rapid formation of Pd black and catalyst deactivation occurred in the absence of DMSO.…”

Intramolecular hydrogen transfer reactions catalyzed by pentamethylcyclopentadienyl rhodium and cobalt olefin complexes: Mechanistic studies

“…[12,13] In a series of elegant studies the authors demonstrated Pd II salts coupled with O 2 as the oxidant (acceptor) to be an effective system for the aerobic dehydrogenation of cyclic ketones to generate α,β unsaturated ketones and phenols. [14]…”