Franziska Schoenebeck

Solvent Effect on Palladium‐Catalyzed Cross‐Coupling Reactions and Implications on the Active Catalytic Species

Suzuki coupling of the bifunctional substrate 1 using [Pd(2)(dba)(3)]/PtBu(3) gives selectivity for C-Cl in nonpolar solvents but for C-OTf in polar solvents. The results of computational and experimental studies suggest that the catalytically active species in polar solvents under conditions employing coordinating additives is inconsistent with monoligated [Pd(PtBu(3))]. Instead, the data are consistent with an anionic palladium complex as the active species.

Redox Reactions in Palladium Catalysis: On the Accelerating and/or Inhibiting Effects of Copper and Silver Salt Additives in Cross‐Coupling Chemistry Involving Electron‐rich Phosphine Ligands

Challenging a catalytic cycle: Pd(0) catalysts are readily oxidized by Cu and Ag salts to give dinuclear Pd(I) complexes and Cu(I) or Ag(I) cubanes (see scheme). The reactivities of the resulting Pd(I) dimers are consistent with several observations of additive effects in cross-coupling chemistry. The results indicate the possibility for alternative catalytic cycles involving dinuclear Pd(I) complexes over the currently accepted synergistic cycles involving Pd(0)/Pd(II) intermediates and Cu or Ag.

On the role of anionic ligands in the site-selectivity of oxidative C–H functionalization reactions of arenes

The replacement of an acetate ligand for carbonate leads to a reversal in site-selectivity in the Pd-mediated C–H oxidative coupling of benzo[h]quinoline with 1,3-dimethoxybenzene. This report describes Density Functional Theory studies designed to elucidate the origin of this selectivity change. These studies focused on two key mechanistic steps: C–H activation and C–C bond-forming reductive elimination. We considered monometallic and bimetallic reaction pathways for acetate and carbonate conditions. The favored C–H activation pathway proceeds via a concerted metalation deprotonation (CMD) mechanism, independent of the nature of anionic ligand (acetate versus carbonate). The predicted selectivity is ortho/para for the C–H activation for both the acetate and carbonate-ligated Pd complexes. Further, we determined that the reductive elimination step is greatly facilitated by the coordination of benzoquinone (by ΔΔG‡ ∼ 20 kcal mol−1) and is predicted to be meta–meta selective with both anionic ligands. Overall, the DFT studies indicate that the anionic ligand does not induce a mechanism change at the elementary steps, and the predicted selectivity at all steps is equivalent for carbonate and acetate, no matter whether a dinuclear or mononuclear pathway is considered. These studies lead us to propose that the role of the anionic ligand is to control which step of the mechanism is overall selectivity-determining. This proposal has been tested experimentally using appropriately designed experiments. Notably, the insoluble base MgO as an acid trap under acetate conditions (with the aim of making the C–H insertion step less reversible), gave rise to predominant ortho/para selectivity in the presence of acetate, in analogy to the results previously seen under carbonate conditions.

A Computational Study of the Origin of Stereoinduction in NHC-Catalyzed Annulation Reactions of α,β-Unsaturated Acyl Azoliums.

The origin of stereoselectivity of NHC-catalyzed annulation reactions of ynals and stable enols was studied with Density Functional Theory. The data suggest that the C-C bond formation is the stereo-determining step. Only the deprotonated pathway (containing an oxy anion and overall neutral species) was found to give rise to discrimination of the competing stereoisomers. This is due predominantly to electrostatic repulsion of the β-stabilizing enolate functionality with the π-cloud of the aryl group in the NHC-catalyst.

Electron Transfer to Benzenes by Photoactivated Neutral Organic Electron Donor Molecules

Simple organic electron donors, composed solely of the elements carbon, hydrogen, and nitrogen, upon photoactivation, reduce ground-state benzene rings to their radical anions by electron transfer (DMF=dimethylformamide)

Computational Ligand Design for the Reductive Elimination of ArCF3 from a Small Bite Angle PdII Complex: Remarkable Effect of a Perfluoroalkyl Phosphine

To date only three ligands are known to trigger the challenging reductive elimination of ArCF3 from Pd(II). We report the computational design of a bidentate trifluoromethylphosphine ligand that although exhibiting a generally ineffective small bite angle is predicted to give facile reductive elimination. Our experimental verification gave quantitative formation of ArCF3 at 80u2009°C within 2u2005h. This highlights the distinct effect of P-CF3 in organometallic reactivity and constitutes a proof-of-principle study of computational reactivity design.

Reductive Elimination of ArCF3 from Bidentate PdII Complexes: A Computational Study

The reductive eliminations of ArCF(3) from Pd(II) complexes bearing small- and large-bite-angle phosphane ligands have been investigated using computational methods. QM/QM and QM/MM studies were applied and complemented with CP2K molecular dynamics investigations. The ligand substituents were varied and a decomposition analysis was performed to allow us to gain insights into the steric and electronic properties of the ligands. The greater reactivity of Xantphos-derived (Xantphos=4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) complexes in the reductive elimination of ArCF(3) is primarily due to the lower repulsive effect of the phoshine substituents in the transition state than in the reactant complex, combined with the increased electronic interaction in the transition state. For DPPE (1,2-bis(diphenylphosphino)ethane), the steric effect of the ligand substituents is greater in the transition state, leading to a higher reaction barrier overall for reductive elimination. There is no direct correlation of the reactivity with the bite angle of the reactant complexes. Only for complexes with large ligand substituents may the bite angle of the Pd complexes be used as a guide for reactivity.

Tandem nucleophilic addition/oxy-2-azonia-Cope rearrangement for the formation of homoallylic amides and lactams: total synthesis and structural verification of motuporamine G.

In the presence of a Lewis acid, β,γ-unsaturated ketones and oximes or imines undergo nucleophilic addition to produce zwitterion intermediates, and subsequent oxy-2-azonia-Cope rearrangements give homoallylic amides. In the case of 2-vinylcycloalkanones, the process results in ring enlargement, providing a novel route to 9- to 16-membered lactams. The preparative significance of this protocol was evidenced by a short synthesis of macrocyclic alkaloid motuporamine G. The stereochemistry-defining step of this oxy-azonia-Cope rearrangement was further studied computationally. Despite a high-energy preequilibrium in the formation of zwitterionic intermediates, the [3,3]-sigmatropic step is the rate- and product-determining step. Chairlike transition states are generally preferred over boatlike ones.

Trifluoromethylation of Ketones and Aldehydes with Bu3SnCF3

The (trifluoromethyl)stannane reagent, Bu3SnCF3, was found to react under CsF activation with ketones and aldehydes to the corresponding trifluoromethylated stannane ether intermediates at room temperature in high yield. Only a mildly acidic extraction (aqueous NH4Cl) is required to release the corresponding trifluoromethyl alcohol products. The protocol is compatible with acid-sensitive functional groups.