Mechanisms of Mn(V)-Oxo to Mn(IV)-Oxyl Conversion: From Closed-Cubane Photosystem II to Mn(V) Catalysts and the Role of the Entering Ligands.

The low activation barrier for O-O coupling in the closed-cubane Oxygen-Evolving Centre (OEC) of Photosystem II (PSII) requires water coordination with the Mn4 'dangler' ion in the Mn(V)-oxo fragment. This coordination transforms the Mn(V)-oxo complex into a more reactive Mn4(IV)-oxyl species, enhancing O-O coupling. This study explains the mechanism behind the coordination and indicates that in the most stable form of the OEC, the Mn4 fragment adopts a trigonal bipyramidal geometry but needs to transition to a square pyramidal form to be activated for O-O coupling. This transition stabilizes the Mn4 dxy orbital, enabling electron transfer from the oxo ligand to the dxy orbital, converting the oxo ligand into an oxyl species. The role of the water is to coordinate with the square pyramidal structure, reducing the energy gap between the oxo and oxyl forms, thereby lowering the activation energy for O-O coupling. This mechanism applies not only to the OEC system but also to other Mn(V)-based catalysts. For other catalysts, ligands such as OH- stabilize the Mn(IV)-oxyl species better than water, improving catalyst activation for reactions like C-H bond activation. This study is the first to explain the Mn(V)-oxo to Mn(IV)-oxyl conversion, providing a new foundation for Mn-based catalyst design.

Advancing Gold Redox Catalysis: Mechanistic Insights, Nucleophilicity-Guided Transmetalation, and Predictive Frameworks for the Oxidation of Aryl Gold(I) Complexes.

Gold redox catalysis, often facilitated by hypervalent iodine(III) reagents, offers unique reactivity but its progress is mainly hindered by an incomplete mechanistic understanding. In this study, we investigated the reaction between the gold(I) complexes [(aryl)Au(PR3 )] and the hypervalent iodine(III) reagent PhICl2 , both experimentally and computationally and provided an explanation for the formation of divergent products as the ligands bonded to the gold(I) center change. We tackled this essential question by uncovering an intriguing transmetalation mechanism that takes place between gold(I) and gold(III) complexes. We found that the ease of transmetalation is governed by the nucleophilicity of the gold(I) complex, [(aryl)Au(PR3 )], with greater nucleophilicity leading to a lower activation energy barrier. Remarkably, transmetalation is mainly controlled by a single orbital - the gold dx 2 -y 2 orbital. This orbital also has a profound influence on the reactivity of the oxidative addition step. In this way, the fundamental mechanistic basis of divergent outcomes in reactions of aryl gold(I) complexes with PhICl2 was established and these observations are reconciled from first principles. The theoretical model developed in this study provides a conceptual framework for anticipating the outcomes of reactions involving [(aryl)Au(PR3 )] with PhICl2 , thereby establishing a solid foundation for further advancements in this field.

Gold(I)-Catalyzed Intramolecular 7-endo-dig Cyclization of Triene-Yne Systems: New Access towards Azulenothiophenes.

We report the direct synthesis of new azulene derivatives through gold-catalyzed cyclization reactions. A five-membered ring as backbone in the applied triene-yne substrates turned out to be crucial to induce the 7-endo-dig cyclization mode necessary to trigger azulene formation. The obtained targets are of high interest due to their potential applications in different fields, like organic materials, medicine or cosmetics. UV/Vis spectra and cyclic voltammetry were measured, based on these the electronic properties were determined. Short two or three step sequences towards the applied starting materials make this approach synthetically highly attractive.

Factors Influencing the Chemoselectivity of Pd(OAc)2 -Catalyzed Cyclization Reactions Involving 1,6-Enynes as a Substrate and PhI(OAc)2 as a Reagent.

It is well documented in the literature that 1,6-enynes are cyclized using PhI(OAc)2 (PIDA) in the presence of Pd(OAc)2 as a catalyst to yield cyclopropyl ketones. In contrast, it has been reported that when 1,6-enynes are substituted by a hydroxy group at the α-position to the alkyne, the chemoselectivity of the cyclization reaction is altered, and polycyclic oxa-heterocycles are formed. This suggests that the hydroxy substituent plays a crucial role in changing the mechanism of the reaction. The aim of this study is to use density functional theory (DFT) calculations at the SMD/M06-D3/def2TZVP//SMD/M06/SDD,6-31G(d) level of theory to shed light on the reason for this change by investigating the detailed mechanistic aspects of these transformations. This study demonstrates that the electronic nature of the Pd catalyst changes from π-philicity to oxophilicity during the catalytic cycle, and this change plays an essential role in controlling the chemoselectivity of the cyclization reactions. In addition, it was found that (1) the hypervalent iodine reagent PIDA serves not only as an oxidant for the oxidation of Pd(II) to Pd(IV), but also as a nucleophile that drives the acetoxypalladation step of the reaction, (2) the oxidation of Pd(II) to Pd(IV) by the iodonium ion [PhIOAc]+ occurs via an interesting mechanism involving coordination of [PhIOAc]+ to the Pd(II) centre, followed by a twist in the hypervalent iodine, and (3) Pd π-complexes are not very susceptible to oxidation. (4) A Pd(II) complex can be six coordinate if the Pd centre is partially oxidized.

Dipole-Transmissive 1,3-Dipolar Cycloadditions for the Rapid Construction of Polycyclic N-Heterocycles: Synthetic and Mechanistic Investigations.

The investigation of distinctive dipole-transmissive dipolar cycloaddition (DTDC) methodology and the formalisation of this concept is reported. A DTDC procedure was able to be developed by taking advantage of the structural complementarity of azide and diazoalkane 1,3-dipoles. Intramolecular azide-alkene 1,3-DCs followed by spontaneous dipole transmission upon work-up furnished intermediate α-diazoisoindole and α-diazoisoquinoline substrates bearing the key secondary diazoalkane 1,3-dipole. N-Derivatisation of the intermediate α-diazoisoindole and α-diazoisoquinolines with a tethered secondary dipolarophile followed by a subsequent 1,3-DC allowed for rapid construction of a range of functionalised polycyclic N-heterocycles. Integrated experimental and theoretical studies established requirements for product formation and revealed the likely mechanistic basis of divergent reactivity observed.

Understanding the Influence of Donor-Acceptor Diazo Compounds on the Catalyst Efficiency of B(C6 F5 )3 Towards Carbene Formation.

Diazo compounds have been largely used as carbene precursors for carbene transfer reactions in a variety of functionalization reactions. However, the ease of carbene generation from the corresponding diazo compounds depends upon the electron donating/withdrawing substituents either side of the diazo functionality. These groups strongly impact the ease of N2 release. Recently, tris(pentafluorophenyl)borane [B(C6 F5 )3 ] has been shown to be an alternative transition metal-free catalyst for carbene transfer reactions. Herein, a density functional theory (DFT) study on the generation of carbene species from α-aryl α-diazocarbonyl compounds using catalytic amounts of B(C6 F5 )3 is reported. The significant finding is that the efficiency of the catalyst depends directly on the nature of the substituents on both the aryl ring and the carbonyl group of the substrate. In some cases, the boron catalyst has negligible effect on the ease of the carbene formation, while in other cases there is a dramatic reduction in the activation energy of the reaction. This direct dependence is not commonly observed in catalysis and this finding opens the way for intelligent design of this and other similar catalytic reactions.

Lewis Acid Assisted Brønsted Acid Catalysed Decarbonylation of Isocyanates: A Combined DFT and Experimental Study.

An efficient and mild reaction protocol for the decarbonylation of isocyanates has been developed using catalytic amounts of Lewis acidic boranes. The electronic nature (electron withdrawing, electron neutral, and electron donating) and the position of the substituents (ortho/meta/para) bound to isocyanate controls the chain length and composition of the products formed in the reaction. Detailed DFT studies were undertaken to account for the formation of the mono/di-carboxamidation products and benzoxazolone compounds.

A Rare Alder-ene Cycloisomerization of 1,6-Allenynes.

Thermally induced cycloisomerization reactions of 1,6-allenynes gives α-methylene-γ-lactams via intramolecular Alder-ene reactions. The mechanism is supported by computational and deuterium labelling studies. This thermal, non-radical method enables the discovery of a hitherto unknown route that proceeds via a divergent mechanism distinct from the previous [2+2] cycloisomerization manifold.

Discovery of Periodinane Oxy-Assisted (POA) Oxidation Mechanism in the IBX-Controlled Oxidative Dearomatization of Pyrroles Mediated by Acetic Acid.

The 2-iodoxybenzoic acid (IBX)-controlled oxidative dearomatization of pyrroles occurs very slowly (or not all) in many organic solvents, including DMSO in which IBX is soluble. Interestingly, although IBX is only partially soluble in acetic acid, this solvent mediates the pyrrole oxidative dearomatization. With the aid of density functional theory (DFT) calculations, we have discovered a new mode of reactivity, termed the periodinane oxy-assisted (POA) oxidation mechanism, which explains this observation.

Site-Selective Csp3-Csp/Csp3-Csp2 Cross-Coupling Reactions Using Frustrated Lewis Pairs.

The donor-acceptor ability of frustrated Lewis pairs (FLPs) has led to widespread applications in organic synthesis. Single electron transfer from a donor Lewis base to an acceptor Lewis acid can generate a frustrated radical pair (FRP) depending on the substrate and energy required (thermal or photochemical) to promote an FLP into an FRP system. Herein, we report the Csp3-Csp cross-coupling reaction of aryl esters with terminal alkynes using the B(C6F5)3/Mes3P FLP. Significantly, when the 1-ethynyl-4-vinylbenzene substrate was employed, the exclusive formation of Csp3-Csp cross-coupled products was observed. However, when 1-ethynyl-2-vinylbenzene was employed, solvent-dependent site-selective Csp3-Csp or Csp3-Csp2 cross-coupling resulted. The nature of these reaction pathways and their selectivity has been investigated by extensive electron paramagnetic resonance (EPR) studies, kinetic studies, and density functional theory (DFT) calculations both to elucidate the mechanism of these coupling reactions and to explain the solvent-dependent site selectivity.

Computational Study of Bridge Splitting, Aryl Halide Oxidative Addition to PtII , and Reductive Elimination from PtIV : Route to Pincer-PtII Reagents with Chemical and Biological Applications.

Density functional theory computation indicates that bridge splitting of [PtII R2 (µ-SEt2 )]2 proceeds by partial dissociation to form R2 Pta (µ-SEt2 )Ptb R2 (SEt2 ), followed by coordination of N-donor bromoarenes (L-Br) at Pta leading to release of Ptb R2 (SEt2 ), which reacts with a second molecule of L-Br, providing two molecules of PtR2 (SEt2 )(L-Br-N). For R=4-tolyl (Tol), L-Br=2,6-(pzCH2 )2 C6 H3 Br (pz=pyrazol-1-yl) and 2,6-(Me2 NCH2 )2 C6 H3 Br, subsequent oxidative addition assisted by intramolecular N-donor coordination via PtII Tol2 (L-N,Br) and reductive elimination from PtIV intermediates gives mer-PtII (L-N,C,N)Br and Tol2 . The strong σ-donor influence of Tol groups results in subtle differences in oxidative addition mechanisms when compared with related aryl halide oxidative addition to palladium(II) centres. For R=Me and L-Br=2,6-(pzCH2 )2 C6 H3 Br, a stable PtIV product, fac-PtIV Me2 {2,6-(pzCH2 )2 C6 H3 -N,C,N)Br is predicted, as reported experimentally, acting as a model for undetected and unstable PtIV Tol2 {L-N,C,N}Br undergoing facile Tol2 reductive elimination. The mechanisms reported herein enable the synthesis of PtII pincer reagents with applications in materials and bio-organometallic chemistry.

Gold-Catalyzed Annulation of 1,8-Dialkynylnaphthalenes: Synthesis and Photoelectric Properties of Indenophenalene-Based Derivatives.

A simple gold-catalyzed annulation of 1,8-dialkynylnaphthalenes utilizing a cationic gold catalyst was developed. Such a peri-position of two alkynyl substituents has not been studied in gold catalysis before. Dependent on the substrate, the reactions either follow a mechanism involving vinyl cation intermediates or involve a dual gold catalysis mechanism which in an initial 6-endo-dig-cyclization generates gold(I) vinylidene intermediates that are able to insert into C-H bonds. Indenophenalene derivatives were obtained in moderate to high yields. In addition, the bidirectional gold-catalyzed annulation of tetraynes provided even larger conjugated π-systems. The optoelectronic properties of the products were also investigated.

Photochemical Activation of a Hydroxyquinone-Derived Phenyliodonium Ylide by Visible Light: Synthetic and Mechanistic Investigations.

We have identified and extensively investigated the photochemical activation and reaction of a hydroxyquinone-derived phenyliodonium ylide in the presence of visible light using experiment and theory. These studies revealed that in its photoexcited state this iodonium is capable of facilitating a range of single-electron transfer (SET) processes, including hydrogen atom transfer (HAT), a Povarov-type reaction, and atom-transfer radical addition chemistry. Where possible, we have employed density functional theory (DFT) to develop a more complete understanding of these photoinduced synthetic transformations.

Oxidation of Electron-Deficient Phenols Mediated by Hypervalent Iodine(V) Reagents: Fundamental Mechanistic Features Revealed by a Density Functional Theory-Based Investigation.

Hypervalent iodine (HVI) compounds are efficient reagents for the double oxidative dearomatization of electron-rich phenols to o-quinones. We recently reported that an underexplored class of iodine(V) reagents possessing bidentate bipyridine ligands, termed Bi(N)-HVIs, could dearomatize electron-poor phenols for the first time. To understand the fundamental mechanistic basis of this unique reactivity, density functional theory (DFT) was utilized. In this way, different pathways were explored to determine why Bi(N)-HVIs are capable of facilitating these challenging transformations while more traditional hypervalent species, such as 2-iodoxybenzoic acid (IBX), cannot. Our calculations reveal that the first redox process is the rate-determining step, the barrier of which hinges on the identity of the ligands bound to the iodine(V) center. This crucial process is composed of three steps: (a) ligand exchange, (b) hypervalent twist, and (c) reductive elimination. We found that strong coordinating ligands disfavor these elementary steps, and, for this reason, HVIs bearing such ligands cannot oxidize the electron-poor phenols. In contrast, the weakly coordinating triflate ligands in Bi(N)-HVIs allow for the kinetically favorable oxidation. It was identified that trapping in situ-generated triflic acid is a key role played by the bidentate bipyridine ligands in Bi(N)-HVIs as this serves to minimize the decomposition of the ortho-quinone product.

Bidentate Nitrogen-Ligated I(V) Reagents, Bi(N)-HVIs: Preparation, Stability, Structure, and Reactivity.

Hypervalent iodine(V) reagents are a powerful class of organic oxidants. While the use of I(V) compounds Dess-Martin periodinane and IBX is widespread, this reagent class has long been plagued by issues of solubility and stability. Extensive effort has been made for derivatizing these scaffolds to modulate reactivity and physical properties but considerable room for innovation still exists. Herein, we describe the preparation, thermal stability, optimized geometries, and synthetic utility of an emerging class of I(V) reagents, Bi(N)-HVIs, possessing datively bound bidentate nitrogen ligands on the iodine center. Bi(N)-HVIs display favorable safety profiles, improved solubility, and comparable to superior oxidative reactivity relative to common I(V) reagents. The highly modular synthesis and in situ generation of Bi(N)-HVIs provides a novel and convenient screening platform for I(V) reagent and reaction development.

Computational Investigation into the Mechanistic Features of Bromide-Catalyzed Alcohol Oxidation by PhIO in Water.

Iodosobenzene (PhIO) is known to be a potent oxidant for alcohols in the presence of catalytic bromide in water. In order to understand this important and practical oxidation process, we have conducted density functional theory studies to shed light on the reaction mechanism. The key finding of this study is that PhIO is not the reactive oxidant itself. Instead, the active oxidant is hypobromite (BrO-), which is generated by the reaction of PhIO with bromide through an SN2-type reaction. Critically, water acts as a cocatalyst in the generation of BrO- through lowering the activation energy of this process. This investigation also demonstrates why BrO- is a more powerful oxidant than PhIO in the oxidation of alcohols. Other halide additives have been reported experimentally to be less effective catalysts than bromide-our calculations provide a clear rationale for these observations. We also examined the effect of replacing water with methanol on the ease of the SN2 reaction, finding that the replacement resulted in a higher activation barrier for the generation of BrO-. Overall, this work demonstrates that the hypervalent iodine(III) reagent PhIO can act as a convenient and controlled precursor of the oxidant hypobromite if the right conditions are present.

Tris(pentafluorophenyl)borane-Catalyzed Carbenium Ion Generation and Autocatalytic Pyrazole Synthesis-A Computational and Experimental Study.

In recent years, metal-free organic synthesis using triarylboranes as catalysts has become a prevalent research area. Herein we report a comprehensive computational and experimental study for the highly selective synthesis of N-substituted pyrazoles through the generation of carbenium species from the reaction between aryl esters and vinyl diazoacetates in the presence of catalytic tris(pentafluorophenyl)borane [B(C6 F5 )3 ]. DFT studies were undertaken to illuminate the reaction mechanism revealing that the in situ generation of a carbenium species acts as an autocatalyst to prompt the regiospecific formation of N-substituted pyrazoles in good to excellent yields (up to 81 %).

Computational Analysis of Mesomerism in para-Substituted mer-NCN Pincer Platinum(II) Complexes, Including its Relationships with Hammett σp Substituent Parameters.

Density Functional Theory studies of square-planar PtII pincer structures, (4-Z-NCN)PtCl ([4-Z-NCN]- =[4-Z-2,6-(Me2 NCH2 )2 C6 H2 -N,C,N]- , Z=H, NO2 , CF3 , CO2 H, CHO, Cl, Br, I, F, SMe, SiMe3 , tBu, OH, NH2 , NMe2 ), enable characterisation of mesomerism for the pincer-Pt interaction. Relationships between Hammett σp substituent parameters of Z and DFT data obtained from NBO6 and AOMix computation are used to probe the interaction of the 5dyz orbital of platinum with π-orbitals of the arene ring. Analogous computation for 2,6-(Me2 CH2 )2 C6 H3 Z (Z=H, CF3 , CHO, Cl, Br, I, F, SMe, SiMe3 , tBu, OH, NH2 ) and (4-H-NCN)PtZ allows an estimation of the relative substituent effects of "(CH2 NMe2 )2 PtZ" on π-delocalisation in the pincer system.

DFT-Based Comparison between Mechanistic Aspects of Amine and Alcohol Oxidation Mediated by IBX.

Density functional theory was utilized to investigate plausible mechanisms for amine and alcohol oxidation by an iodine(V) hypervalent reagent (IBX). In this contribution, we found that amine and alcohol oxidation both proceed by similar mechanisms. The reactions initiate from ligand exchange to give four coordinate intermediates followed by a redox process giving an iodine(III) species and oxidized substrates. Interestingly, for both the ligand-exchange and the redox steps a hypervalent twist is required for the reaction to proceed via an energetically more accessible route. The ligand-exchange process was found to be mediated by a proton-shuttling agent such as water, a second IBX, or a second substrate. While the ligand-exchange step for both amine and alcohol occurs with almost identical activation energy (particularly when water is considered as the shuttling agent), the redox step for the amine takes place with much lower activation energy than that for the alcohol. Finally, we ascertained that five coordinate amide iodine(V) complexes are unreactive toward redox reactions due to the fact that in such cases two electrons from the coordinated amide are required to occupy a 3c-4e σ* orbital which is too high in energy to be reachable.

Mechanistic investigation into phenol oxidation by IBX elucidated by DFT calculations.

Density functional theory (DFT) at the SMD/M06-2X/def2-TZVP//SMD/M06-2X/LANL2DZ(d),6-31G(d) level was used to explore the regioselective double oxidation of phenols by a hypervalent iodine(v) reagent (IBX) to give o-quinones. The oxidative dearomatization commences with the ligand exchange between IBX and phenol, yielding a phenolate complex, followed by the first redox process, which reduces iodine(v) to iodine(iii). Both the processes (the ligand exchange and the first redox reaction) were found to be mediated by a less stable isomer of iodine(v) species. We found that although the first redox process preferentially proceeds via an associative pathway, an electron withdrawing substituent on the phenol ring decreases its accessibility. The inspection of the electronic structure of the redox transition state indicates that the phenolate involved in the iodine(v) reduction has some phenoxenium character. The intrinsic stability of a phenoxenium ion is calculated to be highly sensitive to the substituent on the phenol ring. Since the electron withdrawing substituents considerably decrease the stability of the phenoxenium, they render the iodine(v) to iodine(iii) reduction energy consuming. Once the first redox step has completed, a catechol-iodine(iii) complex is formed, from which the second redox process produces the final o-quinone product via a carboxylate-assisted transition structure. This transition structure gains stability by hydrogen bond interaction between the catechol OH and carboxylate group. Such an interaction results in the phenolate not having any phenoxenium character in the transition structure, thus making the activation barrier to the second redox step independent from the substituent on the phenol ring.