Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights

Radical-radical couplings are mostly nearly diffusion-controlled processes. Therefore, the selective cross-coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if the radicals have different lifetimes and if they are generated at equal rates, cross-coupling will become the dominant process. This high cross-selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this Review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes, and various examples of PRE-mediated radical-radical couplings in synthesis are summarized. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer-lived than the other transient radical, the PRE operates and high cross-selectivity is achieved. This important point expands the scope of PRE-mediated radical chemistry. The Review is divided into two parts, namely 1) the coupling of persistent or longer-lived organic radicals and 2) "radical-metal crossover reactions"; here, metal-centered radical species and more generally longer-lived transition-metal complexes that are able to react with radicals are discussed-a field that has flourished recently.

The Persistent Radical Effect in Organic Synthesis

Understanding the mechanisms of chemical reactions, especially catalysis, has been an important and active area of computational organic chemistry, and close collaborations between experimentalists and theorists represent a growing trend. This Perspective provides examples of such productive collaborations. The understanding of various reaction mechanisms and the insight gained from these studies are emphasized. The applications of various experimental techniques in elucidation of reaction details as well as the development of various computational techniques to meet the demand of emerging synthetic methods, e.g., C–H activation, organocatalysis, and single electron transfer, are presented along with some conventional developments of mechanistic aspects. Examples of applications are selected to demonstrate the advantages and limitations of these techniques. Some challenges in the mechanistic studies and predictions of reactions are also analyzed.

Computational Organic Chemistry: Bridging Theory and Experiment in Establishing the Mechanisms of Chemical Reactions

ConspectusWe present a new and efficient strategy for the atom-economic transformation of both alkynes and allenes to allylic functionalized structures via a Rh-catalyzed isomerization/addition reaction which has been developed in our working group. Our methodology thus grants access to an important structural class valued in modern organic chemistry for both its versatility for further functionalization and the potential for asymmetric synthesis with the construction of a new stereogenic center. This new methodology, inspired by mechanistic investigations by Werner in the late 1980s and based on preliminary work by Yamamoto and Trost, offers an attractive alternative to other established methods for allylic functionalization such as allylic substitution or allylic oxidation. The main advantage of our methodology consists of the inherent atom economy in comparison to allylic oxidation or substitution, which both produce stoichiometric amounts of waste and, in case of the substitution reaction, require pre...

Branching Out: Rhodium-Catalyzed Allylation with Alkynes and Allenes

Hydrofunctionalisation and difunctionalisation of dienes, allenes, and alkynes are widely utilized in the synthesis of valuable allylic compounds. In the past decades, asymmetric catalysis has emerged as one of the most attractive fields in organic synthesis. Recently, the asymmetric versions of hydrofunctionalisation and difunctionalisation reactions have become powerful and compelling tools to afford enantiopure allylic compounds, appealing to a large range of chemists. Various metal complexes modified with a large number of chiral ligands and several chiral organocatalysts have been developed to promote the hydrofunctionalisation and difunctionalisation reactions and expand substrate scope. This review provides an overview of this field, and aims at summarizing the chiral ligand used in this area of research. A detailed discussion of the development of these reactions and the general reaction mechanisms is provided.

Asymmetric synthesis of allylic compounds via hydrofunctionalisation and difunctionalisation of dienes, allenes, and alkynes.

Previously we reported the redox-neutral atom economic rhodium catalyzed coupling of terminal alkynes with carboxylic acids using the DPEphos ligand. We herein present a thorough mechanistic investigation applying various spectroscopic and spectrometric methods (NMR, in situ-IR, ESI-MS) in combination with DFT calculations. Our findings show that in contrast to the originally proposed mechanism, the catalytic cycle involves an intramolecular protonation and not an oxidative insertion of rhodium in the OH bond of the carboxylic acid. A σ-allyl complex was identified as the resting state of the catalytic transformation and characterized by X-ray crystallographic analysis. By means of ESI-MS investigations we were able to detect a reactive intermediate of the catalytic cycle.

Mechanistic Investigations of the Rhodium Catalyzed Propargylic CH Activation

To develop more active catalysts for the rhodium-catalyzed addition of carboxylic acids to terminal alkynes furnishing anti-Markovnikov Z enol esters, a thorough study of the rhodium complexes involved was performed. A number of rhodium complexes were characterized by NMR, ESI-MS, and X-ray analysis and applied as catalysts for the title reaction. The systematic investigations revealed that the presence of chloride ions decreased the catalyst activity. Conversely, generating and applying a mixture of two rhodium species, namely, [Rh(DPPMP)2][H(benzoate)2] (DPPMP=diphenylphosphinomethylpyridine) and [{Rh(COD)(μ2-benzoate)}2], provided a significantly more active catalyst. Furthermore, the addition of a catalytic amount of base (Cs2CO3) had an additional accelerating effect. This higher catalyst activity allowed the reaction time to be reduced from 16 to 1–4 h while maintaining high selectivity. Studies on the substrate scope revealed that the new catalysts have greater functional-group compatibility.

Development of an improved rhodium catalyst for z-selective anti-markovnikov addition of carboxylic acids to terminal alkynes.

Rhodium diphosphine complexes: a case study for catalyst activation and deactivation

As the workhorses for many applications, neutral dimeric μ2-X-bridged diphosphine rhodium complexes of the type [{Rh(diphosphine)(μ2-X)}2] (X=Cl, OH) are usually prepared in situ by the addition of diphosphine ligands to the rhodium complex [{Rh(diolefin)(μ2-X)}2] (diolefin=cyclooctadiene (cod) or norbornadiene (nbd)) or [{Rh(monoolefin)2(μ2-Cl)}2] (monoolefin=cyclooctene (coe) or ethylene (C2H4)). The in situ procedure has been investigated for the diphosphines 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), 5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole (SEGPHOS), 5,5′-bis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxole (DM-SEGPHOS), 5,5′-bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-4,4′-bi-1,3-benzodioxole (DTBM-SEGPHOS), 2,2′-bis(diphenylphosphino)-1,1′-dicyclopentane (BICP), 1-[2-(diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (PPF-PtBu2), 1,1′-bis(diisopropylphosphino)ferrocene (DiPPF), 1,2-bis(diphenylphosphino)ethane (DPPE), 1,2-bis(o-methoxyphenylphosphino)ethane (DIPAMP), 4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxalane (DIOP), 1,2-bis(2,5-dimethylphospholano)benzene (Me-DuPHOS), 1,4-bis(diphenylphosphino)butane (DPPB), and 1,3-bis(diphenylphosphino)propane (DPPP); the resulting complexes have been characterized by 31P NMR spectroscopy and, in most cases, also by X-ray analysis. Depending on the diphosphine ligand, the solvent, the temperature, and the rhodium precursor, species other than the desired one [{Rh(diphosphine)(μ2-X)}2] are formed, for example, [(diolefin)Rh(μ2-Cl)2Rh(diphosphine)], [Rh(diphosphine)(diolefin)]+, [Rh(diphosphine)2]+, and [Rh(diphosphine)(diolefin)(Cl)]. The results clearly show that the in situ method commonly applied for precatalyst preparation cannot be regarded as an optimal strategy for the formation of such neutral [{Rh(diphosphine)(μ2-X)}2] complexes.

Antje Meißner

Papers

Mechanistic Investigations of the Rhodium Catalyzed Propargylic CH Activation

Development of an improved rhodium catalyst for z-selective anti-markovnikov addition of carboxylic acids to terminal alkynes.

Rhodium diphosphine complexes: a case study for catalyst activation and deactivation

In Situ Synthesis of Neutral Dinuclear Rhodium Diphosphine Complexes [{Rh(diphosphine)(μ2‐X)}2]: Systematic Investigations

Halide bridged trinuclear rhodium complexes and their inhibiting influence on catalysis