Mechanism of C−F Reductive Elimination from Palladium(IV) Fluorides

The first systematic mechanism study of C−F reductive elimination from a transition metal complex is described. C−F bond formation from three different Pd(IV) fluoride complexes was mechanistically evaluated. The experimental data suggest that reductive elimination occurs from cationic Pd(IV) fluoride complexes via a dissociative mechanism. The ancillary pyridyl-sulfonamide ligand plays a crucial role for C−F reductive elimination, likely due to a κ^3 coordination mode, in which an oxygen atom of the sulfonyl group coordinates to Pd. The pyridyl-sulfonamide can support Pd(IV) and has the appropriate geometry and electronic structure to induce reductive elimination

Two Metals Are Better Than One in the Gold Catalyzed Oxidative Heteroarylation of Alkenes

We present a detailed study of the mechanism for oxidative heteroarylation, based on DFT calculations and experimental observations. We propose binuclear Au(II)–Au(II) complexes to be key intermediates in the mechanism for gold catalyzed oxidative heteroarylation. The reaction is thought to proceed via a gold redox cycle involving initial oxidation of Au(I) to binuclear Au(II)–Au(II) complexes by Selectfluor, followed by heteroauration and reductive elimination. While it is tempting to invoke a transmetalation/reductive elimination mechanism similar to that proposed for other transition metal complexes, experimental and DFT studies suggest that the key C–C bond forming reaction occurs via a bimolecular reductive elimination process (devoid of transmetalation). In addition, the stereochemistry of the elimination step was determined experimentally to proceed with complete retention. Ligand and halide effects played an important role in the development and optimization of the catalyst; our data provides an explanation for the ligand effects observed experimentally, useful for future catalyst development. Cyclic voltammetry data is presented that supports redox synergy of the Au···Au aurophilic interaction. The monometallic reductive elimination from mononuclear Au(III) complexes is also studied from which we can predict a ~ 15 kcal/mol advantage for bimetallic reductive elimination

Photoinitiated oxidative addition of CF3I to gold(I) and facile aryl-CF3 reductive elimination.

Herein we report the mechanism of oxidative addition of CF3I to Au(I), and remarkably fast Caryl-CF3 bond reductive elimination from Au(III) cations. CF3I undergoes a fast, formal oxidative addition to R3PAuR (R = Cy, R = 3,5-F2-C6H4, 4-F-C6H4, C6H5, 4-Me-C6H4, 4-MeO-C6H4, Me; R = Ph, R = 4-F-C6H4, 4-Me-C6H4). When R = aryl, complexes of the type R3PAu(aryl)(CF3)I can be isolated and characterized. Mechanistic studies suggest that near-ultraviolet light (λmax = 313 nm) photoinitiates a radical chain reaction by exciting CF3I. Complexes supported by PPh3 undergo reversible phosphine dissociation at 110 °C to generate a three-coordinate intermediate that undergoes slow reductive elimination. These processes are quantitative and heavily favor Caryl-I reductive elimination over Caryl-CF3 reductive elimination. Silver-mediated halide abstraction from all complexes of the type R3PAu(aryl)(CF3)I results in quantitative formation of Ar-CF3 in less than 1 min at temperatures as low as -10 °C

Reductive elimination of alkylamines and ethers: reactions of bisphosphine-ligated palladium(II) complexes

The reductive elimination reactions detailed in this dissertation provide experimental insight into the mechanism of reductive elimination to form the C(sp3)-N bond of benzylamines and the C(sp3)-O bond of benzyl ethers. The stereochemical outcome of the reaction indicates an ionic pathway, but the process lacks many of the effects of electronic and solvent perturbations that typically signal an ionic intermediate. We propose that reductive elimination from benzylpalladium(II) amido and aryloxide complexes occurs by dissociation of the amido or aryloxide ligand, followed by nucleophilic attack on the benzyl ligand. The proposed ionic mechanism is more akin to the reductive elimination reactions that occur from high-valent Pt(IV) and Ni(III) complexes than reductive elimination reactions that occur from other Pd(II) complexes. Our data indicate that substantial differences exist between reductive eliminations to form the C(sp3) bonds in ethers and amines from palladium(II). We prepared alkylpalladium(II) amido complexes to study the C(sp3)-N reductive elimination reaction from complexes containing a non-benzylic hydrocarbyl ligand. We investigated a series of alkylpalladium amido complexes and observed reductive elimination occurs from bisphosphine-ligated neopentylpalladium amido complexes in low yield. Reductive elimination from neopentylpalladium amido complexes occurs most likely by a concerted reductive elimination reaction, and is favored by the increased steric bulk of the neopentyl ligand. We also investigated azametallacyclic palladium complexes with a norbornyl hydrocarbyl ligand, and observed reductive elimination occurs to form a norbornyl indoline product. We found that the yield was slightly improved over neopentylpalladium complexes, but that the yield of reductive elimination was low. Finally we investigated non-metallacyclic complexes containing a norbornyl hydrocarbyl ligand. We discovered that reductive elimination occurs in moderate yield, and the reductive elimination product ratio indicates a balance between a concerted and an ionic mechanism. The data presented in this dissertation demonstrate that C(sp3)-N reductive elimination from benzylpalladium(II) and alkylpalladium(II) complexes can occur. We propose an ionic mechanism for the formation of benzylamines and benzyl ethers by reductive elimination from benzylpalladium(II) complexes. Reductive elimination from neopentyl and metallacyclicpalladium(II) complexes likely occurs by a concerted mechanism, demonstrating the importance of steric bulk and metal geometry, respectively. Finally, reductive elimination from non-metallacyclic norbornylpalladium(II) complexes indicates that a concerted and ionic mechanism may occur simultaneously. Although the yield of the alkylamine products is low, the observation that C(sp3)-N reductive elimination occurs from the alkylpalladium complexes provides the first step toward developing a synthetically useful reaction for the formation of C(sp3)-heteroatom bonds from low-valent group 10 complexes without the addition of an oxidant

Mechanistic and computational studies of oxidatively-induced aryl-CF3 bond formation at palladium

This article describes the rational design of 1st generation systems for oxidatively-induced Aryl– CF3 bond-forming reductive elimination from PdII. Treatment of (dtbpy)PdII(Aryl)(CF3) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridium triflate) afforded the isolable PdIV intermediate (dtbpy)PdIV(Aryl)(CF3)(F)(OTf). Thermolysis of this complex at 80 °C resulted in Aryl–CF3 bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this PdIV species proceeds via pre-equilibrium dissociation of TfO− followed by Aryl–CF3 coupling. DFT calculations reveal that the transition state for Aryl–CF3 bond formation involves the CF3 acting as an electrophile with the Aryl ligand acting as a nucleophilic coupling partner. These mechanistic considerations along with DFT calculations have facilitated the design of a 2nd generation system utilizing the tmeda (N,N,N’,N’-tetramethylethylenediamine) ligand in place of dtbpy. The tmeda complexes undergo oxidative trifluoromethylation at room temperature

Synthesis of Cyclopropanes via Organoiron Methodology: Preparation of \u3cem\u3erac\u3c/em\u3e-Dysibetaine Cpa

The cyclopropane containing betaine, rac-dysibetaine CPa, was prepared from (1-methoxycarbonylpentadienyl)-Fe(CO)2PPh3+ by nucleophilic addition of nitromethane anion followed by oxidatively induced reductive elimination

Carbon(sp3)-fluorine bond-forming reductive elimination from palladium(IV) complexes.

The development of transition-metal-catalyzed reactions for the formation of CF bonds has been an area of intense research over the past decade.[1–3] Traditionally, the CF coupling step of these sequences has proven challenging because of the high kinetic barrier for CF bond-forming reductive elimination from most transition-metal centers.[1] Our approach to address this challenge has involved the use of PdII catalysts in conjunction with F+-based oxidants. Since 2006, a variety of PdII-catalyzed reactions of F+ reagents have been developed to introduce fluorine at both C(sp2 ) and C(sp3 ) centers.[4–6] These transformations have been proposed to proceed through CF bond-forming reductive elimination from transient, highly reactive PdIV alkyl/aryl fluoride intermediate

Interplay of water and a supramolecular capsule for catalysis of reductive elimination reaction from gold.

Supramolecular assemblies have gained tremendous attention due to their ability to catalyze reactions with the efficiencies of natural enzymes. Using ab initio molecular dynamics, we identify the origin of the catalysis by the supramolecular capsule Ga4L612- on the reductive elimination reaction from gold complexes and assess their similarity to natural enzymes. By comparing the free energies of the reactants and transition states for the catalyzed and uncatalyzed reactions, we determine that an encapsulated water molecule generates electric fields that contributes the most to the reduction in the activation free energy. Although this is unlike the biomimetic scenario of catalysis through direct host-guest interactions, the electric fields from the nanocage also supports the transition state to complete the reductive elimination reaction with greater catalytic efficiency. However it is also shown that the nanocage poorly organizes the interfacial water, which in turn creates electric fields that misalign with the breaking bonds of the substrate, thus identifying new opportunities for catalytic design improvements in nanocage assemblies

New Reactivity of High Oxidation State Palladium Complexes.

New methodology involving Pd-mediated catalysis that proposes Pd(II/IV) mechanisms has exploded over the past decade. Despite the implication of Pd(IV) intermediates prior to bond-forming C–X reductive elimination in these catalytic reactions, the reported organometallic Pd(IV) complexes in the literature primarily underwent C–C bond-forming reductive elimination. The goal of this dissertation was to design systems to study C–X reductive elimination from observable Pd(IV) complexes. In addition to reductive elimination reactions from Pd(IV), we sought to explore other organometallic reactions at Pd(IV) centers such as C–H activation. The first data chapter presents a detailed mechanistic study of C–O and C–C bond-formation from isolable PdIV complexes. A variety of complexes were synthesized to explore how electronic factors, activation parameters, solvent effects and additive effects are involved in/influence C–O reductive elimination from a PdIV center. Additionally, we identified a system that yielded competing C–O and C–C reductive elimination from PdIV. Therefore, we conducted mechanistic studies to probe C–C bond formation from PdIV; we were able to propose a mechanism for this transformation as well. Chapter 3 investigates sp2 versus sp3-C–X bond formation from PdIV complexes. Interestingly, in all of the systems that were studied, sp3-C–X bond formation out competes sp2 reductive elimination. This chapter presents novel examples of sp3-C–F, C–N and C–O reductive elimination from PdIV in addition to sp3-C–Cl bond-formation. These reactions represent the first examples of high yielding sp3-C–X reductive elimination from PdIV. Lastly, the mechanistic insights gained from these studies lead us to examine systems for sp3-C–X bond-formation that do not use the oxidant to deliver the desired functionality. Next, Chapter 4 of this thesis describes the development a ligand system to explore C–H activation directly at a PdIV center. We designed a complex where reductive elimination is slow and C–H activation is observed. This enabled us to compare the selectively of C–H activation at a PdIV center versus a PdII center. Finally, the thesis concludes with a discussion of the future for the development of PdIV chemistry.Ph.D.ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91616/1/racowski_1.pd