Computational Assessment of the Mechanistic Journey in Chan-Lam-Based Arylation of Imidazoles.

Cu(II)-catalyzed C-N bond formation reactions remain one of most widely practiced and powerful protocols for the synthesis of value-added chemicals, bioactive molecules, and materials. Despite numerous experimental contributions, the overall mechanistic understanding of the C-N coupling reaction based on the Chan-Lam (CL) reaction methodology is still limited and underdeveloped, particularly with respect to the use of different substrates and catalytic species. Herein, we report an in-depth DFT-based study on the mechanism of N-arylation of imidazoles following Collman's experimental setup. Our findings unfold for the first time the ligand-based CL coupling catalyzed by the [Cu(II)(OH)TMEDA]2Cl2 complex. The transmetalation step with an energy span of 26.2 kcal mol-1 is rate-determining, while the subsequent disproportionation and reductive elimination are relatively facile (δE = 16.4 kcal mol-1) in comparison to the CL amination of secondary amines. The final oxidative catalyst regeneration results in the presence of O2, accompanying an energy span of 12.8 kcal mol-1, where hydrogen transfer from the coordinated water allows the reduction of superoxo linkage. Couplings performed in the presence of a combination of bidentate sp3-N ligands with single and double -(CH2)- spacer units afford a kinetically facile transformation (24.5 kcal mol-1). Furthermore, our results agree with the experimental outcomes of regioselective couplings of substituted imidazoles.

Mechanistic Avenues in the Chan-Lam-Based Etherification Reaction: A Computational Exploration.

Ongoing advances in CuII -catalyzed aerobic oxidative coupling reactions between arylboronic esters and diverse heteroatom nucleophiles have strengthened the development of the general Chan-Lam (CL)-based reaction protocol, including C-O bond formation methodologies. In-depth mechanistic understanding of CL etherification with specific emphasis on different reaction routes and their energetics are still lacking, even though the reaction has been experimentally explored. Here, we present a DFT-guided computational study to unravel the mechanistic pathways of CL-based etherification. The computational findings provide some interesting insights into the fundamental steps of the catalytic cycle, particularly the rate-determining transmetalation event. An aryl boronic ester-coordinated, methoxide-bridged CuII intermediate that acts as resting state undergoes transmetalation with an activation barrier of 20.4 kcal mol-1 . The energy spans of the remaining fundamental steps leading to the methoxylated product are relatively low. The minor p-cresol product requires an additional 14.2 kcal mol-1 energy span to surmount in comparison to the favored route. Hammett studies for the substituted aryl boronic esters reveal higher reaction turnovers for electron-rich aryl systems. The results agree with previously reported spectroscopic and kinetic observations. For a series of alcohol substrates, it was observed that, except for cyclohexanol, moderate to high etherification turnovers are predicted.

Mechanistic Avenues in the Chan-Lam-Based Etherification Reaction: A Computational Exploration.

Invited for the cover of this issue is the group of Koley and co-workers at the Indian Institute of Science Education and Research (IISER) Kolkata. The image depicts the industrial generation of the product from the available starting materials in a catalytic cycle. Read the full text of the article at 10.1002/chem.202302983.

Monomeric Magnesium Catalyzed Alkene and Alkyne Hydroboration.

In this work, two monomeric magnesium alkyl complexes (1 and 2) were prepared using bis(phosphino)carbazole framework and among them 1 has been used as a catalyst for hydroboration of alkenes and alkynes with pinacolborane (HBpin). A broad variety of aromatic and aliphatic alkenes and alkynes were efficiently reduced. Anti-Markovnikov regioselective hydroboration of alkenes and alkynes was achieved, which was confirmed by deuterium-labelling experiments. The work represents the first example of the use of magnesium in homogeneous catalytic hydroboration of alkene with broad substrate scope. Experimental mechanistic investigations and DFT calculations provided insights into the reaction mechanism. Finally, the hydroboration protocol was extended to terpenes.

Palladium-Catalyzed para-C-H Arylation of Anilines with Aromatic Halides.

Controlling regioselectivity in C-H functionalizations is a key challenge in chemical method development. In arenes, functionalizations are most difficult to direct towards the C-H group furthest away from a substituent, in its para position. We herein demonstrate how the para-C-H arylation of anilines with non-activated aryl halides, elusive to date, is achieved by a base-assisted "metalla-tautomerism" approach. A proton is abstracted from the aniline substrate and replaced by an arylpalladium species, generated from the aryl halide coupling partner. In this step, the palladium is directed away from the N- to the tautomeric para-C-H position by a large phosphine ligand combined with a triphenylmethyl shielding group. The triphenylmethyl group is easily installed and removed, and can be recycled.

Germyliumylidene: A Versatile Low Valent Group 14 Catalyst.

Bis-NHC stabilized germyliumylidenes [RGe(NHC)2 ]+ are typically Lewis basic (LB) in nature, owing to their lone pair and coordination of two NHCs to the vacant p-orbitals of the germanium center. However, they can also show Lewis acidity (LA) via Ge-CNHC σ* orbital. Utilizing this unique electronic feature, we report the first example of bis-NHC-stabilized germyliumylidene [Mes TerGe(NHC)2 ]Cl (1), (Mes Ter=2,6-(2,4,6-Me3 C6 H2 )2 C6 H3 ; NHC= IMe4 =1,3,4,5-tetramethylimidazol-2-ylidene) catalyzed reduction of CO2 with amines and arylsilane, which proceeds via its Lewis basic nature. In contrast, the Lewis acid nature of 1 is utilized in the catalyzed hydroboration and cyanosilylation of carbonyls, thus highlighting the versatile ambiphilic nature of bis-NHC stabilized germyliumylidenes.

Isomerization of Functionalized Olefins by Using the Dinuclear Catalyst [PdI (µ-Br)(Pt Bu3 )]2 : A Mechanistic Study.

In a combined experimental and computational study, the isomerization activity of the dinuclear palladium(I) complex [PdI (µ-Br)(Pt Bu3 )]2 towards allyl arenes, esters, amides, ethers, and alcohols has been investigated. The calculated energy profiles for catalyst activation for two alternative dinuclear and mononuclear catalytic cycles, and for catalyst deactivation are in good agreement with the experimental results. Comparison of experimentally observed E/Z ratios at incomplete conversion with calculated kinetic selectivities revealed that a substantial amount of product must form via the dinuclear pathway, in which the isomerization is promoted cooperatively by two palladium centers. The dissociation barrier towards mononuclear Pd species is relatively high, and once the catalyst enters the energetically more favorable mononuclear pathway, only a low barrier has to be overcome towards irreversible deactivation.

Computational Investigation of Multifaceted Cationic Rearrangement and Stereo- and Regioselectivity in the Formation of Dysideanone's Analogues.

Mechanistic studies of regiodivergent arylations of cycloalkanols to furnish enantioenriched dysideanone's analogues are performed by employing density functional theory (DFT) calculations (B3LYP-D3(SMD)/6-311++G**//B3LYP-D3/6-31+G** level of theory). On the basis of our calculations, remote γ'-C-H arylation is preferred for unsubstituted carbinol 1, an outcome from combined factors like carbocationic stability, less steric hindrance during C-C coupling, and facile dearomatization. Meanwhile, in the presence of dimethyl substituent 1Me, regioselective γ-arylation is favored by 3.4 kcal/mol, and both findings are in agreement with the reported experimental observations. Most importantly, we concur that the barrier associated with the formation of carbocation 6 and its substituted analogues correlates with the C-H arylation outcomes. Furthermore, the ß-arylation route remains unlikely for all the reaction pathways explored in this study.

Si(II) Cation-Promoted Formation of an Abnormal NHC-Bound Silylene and a cAAC-Silanyl Radical Ion.

The reaction of amidinatosilylene LSi(:)Cl [L = PhC(NtBu)2] with N-heterocyclic carbene IAr [:C{N(Ar)CH}2, where Ar = 2,6-iPr2C6H3] and NaOTf in tetrahydrofuran (THF) facilely afforded a silicon(II) cation [LSi(:)-aIAr]+OTf- (1+OTf-), where IAr isomerizes to abnormal N-heterocyclic carbene aIAr, coordinating to the silicon(II) center. Its Ge homologue, [LGe(:)-aIAr]+OTf- (2+OTf-), was also accessed via the same protocol. For the formation of 1+, we propose that an in situ-generated Si(II) cation [LSi(:)]+ under the treatment of LSi(:)Cl with NaOTf may isomerize IAr in THF. In contrast, the replacement of IAr with cyclic alkyl(amino) carbene (cAAC) furnished a cAAC-silanyl radical ion [LSi(H)-cAAC]•+(LiOTf2)- [3•+(LiOTf2)-], which may undergo an abstraction of the H radical from THF. All of the products were characterized by nuclear magnetic resonance spectroscopy, electron paramagnetic resonance, and X-ray crystallography, and their bonding scenarios were investigated by density functional theory calculations. These studies provide new perspective on carbene-silicon chemistry.

N-Heterocyclic Carbene-Stabilized Germa-acylium Ion: Reactivity and Utility in Catalytic CO2 Functionalizations.

The first acceptor-free heavier germanium analogue of an acylium ion, [RGe(O)(NHC)2]X (R = MesTer = 2,6-(2,4,6-Me3C6H2)2C6H3; NHC = IMe4 = 1,3,4,5-tetramethylimidazol-2-ylidene; X = (Cl or BArF = {(3,5-(CF3)2C6H5)4B}), was isolated by reacting [RGe(NHC)2]X with N2O. Conversion of the germa-acylium ion to the first solely donor-stabilized germanium ester [(NHC)RGe(O)(OSiPh3)] and corresponding heavier analogues ([RGe(S)(NHC)2]X and [RGe(Se)(NHC)2]X) demonstrated its classical acylium-like behavior. The polarized terminal GeO bond in the germa-acylium ion was utilized to activate CO2 and silane, with the former found to be an example of reversible activation of CO2, thus mimicking the behavior of transition metal oxides. Furthermore, its transition-metal-like nature is demonstrated as it was found to be an active catalyst in both CO2 hydrosilylation and reductive N-functionalization of amines using CO2 as the C1 source. Mechanistic studies were undertaken both experimentally and computationally, which revealed that the reaction proceeds via an N-heterocyclic carbene (NHC) siloxygermylene [(NHC)RGe(OSiHPh2)].

Cyclic (Alkyl)(Amino)Carbene-Stabilized Aluminum and Gallium Radicals Based on Amidinate Scaffolds.

Neutral, mononuclear aluminum and gallium radicals, stabilized by cyclic (alkyl)(amino)carbene (cAAC), were synthesized. LMCl2 upon reduction with KC8 in the presence of cAAC afforded the radicals LMCl(cAAC), where L = PhC(NtBu)2 and M = Al (1), Ga (2). The radicals were characterized by X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and mass spectrometry. EPR, SQUID measurement, and computational calculations confirmed paramagnetism of the radicals with unpaired spin mainly on cAAC.

Saturated N-Heterocyclic Carbene Based Thiele's Hydrocarbon with a Tetrafluorophenylene Linker.

The synthesis of a SIPr [1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene] derived Kekulé diradicaloid with a tetrafluorophenylene spacer (3) has been described. Two synthetic routes have been reported to access 3. The cleavage of C-F bond of C6 F6 by SIPr in the presence of BF3 led to double C-F activated compound with two tetrafluoro borate counter anions (2), which upon reduction by lithium metal afforded 3. Alternatively, 3 can be directly accessed in one step by reacting SIPr with C6 F6 in presence of Mg metal. Compounds 2 and 3 were well characterized spectroscopically and by single-crystal X-ray diffraction studies. Experimental and computational studies support the cumulenic closed-shell singlet state of 3 with a singlet-triplet energy gap (ΔES-T ) of 23.7 kcal mol-1 .

Computational Exploration of Mechanistic Avenues in C-H Activation Assisted Pd-Catalyzed Carbonylative Coupling.

The detailed mechanism of the intermolecular Pd-catalyzed carbonylative coupling reaction between aryl bromides and polyfluoroarenes relying on C(sp2)-H activation was investigated using state-of-the-art computational methods (SMD-B3LYP-D3(BJ)/BS2//B3LYP-D3/BS1). The mechanism unveils the necessary and important roles of a slight excess of carbon monoxide: acting as a ligand in the active catalyst state, participating as a reactant in the carbonylation process, and accelerating the final reductive elimination event. Importantly, the desired carbonylative coupling route follows the rate-limiting C-H activation process via the concerted metalation-deprotonation pathway, which is slightly more feasible than the decarboxylative route leading to byproduct formation by 1.2 kcal/mol. The analyses of the free energies indicate that the choice of base has a significant effect on the reaction mechanism and its energetics. The Cs2CO3 base guides the reaction toward the coupling route, whereas carbonate bases such as K2CO3 and Na2CO3 switch toward an undesired decarboxylative path. However, K3PO4 significantly reduces the C-H activation barrier over the decarboxylation reaction barrier and can act as a potential alternative base. The positional influence of a methoxy substituent in bromoanisole and different substituent effects in polyfluoroarenes were also considered. Our results show that different substituents impose significant impact on the desired carbonylative product formation energetics. Considering the influence of several ligands leads to the conclusion that other phosphine and N-heterocyclic carbene, such as P nBuAd2 and IMes, can be used as an efficient alternative than the experimentally reported P tBu3 ligand exhibiting a clear preference for C-H activation (ΔΔ⧧ GLS) by 7.1 and 10.9 kcal/mol, respectively. We have also utilized the energetic span model to interpret the experimental results. Moreover, to elucidate the origin of activation barriers, energy decomposition analysis calculations were accomplished for the critical transition states populating the energy profiles.

Donor Stabilized Diatomic Gr.14 E2 (E = C-Pb) Molecule D-E2-D (D = NHC, aNHC, NNHC, NHSi, NHGe, cAAC, cAASi, cAAGe): A Theoretical Insight.

Quantum chemical calculations have been carried out to explore the detailed electronic structure and bonding scenario in various bis-donor stabilized E2 compounds (E = C-Pb). Our computational findings reveal that the thermodynamic stabilities of the E2 core gradually decrease as we move down the group. A linear D-E-E'-D framework is observed for C2 systems, while the heavier group 14 analogues possess trans-bent geometries. Consideration of few compounds as viable targets for synthesis is suggested by their corresponding calculated formation energies. In addition, the thermodynamic stabilities of C2 systems notably increase with the saturation of the donor ring framework and are even more pronounced for boron-substituted saturated NHD ligand. QTAIM calculations affirmed that the covalent nature of E-E' bonds shifts toward the donor-acceptor region as one traverses from top to bottom along group 14. The E-D and E'-D bonds in the C2 systems have covalent nature, whereas those in Si2-Pb2 systems are characterized by donor-acceptor bonds. In addition, we have computed proton affinities and vertical ionization potentials (VIPs) of these compounds. An excellent correlation was obtained between calculated VIPs and orbital energies of HOMOs. Furthermore, in the present study, we also explored the effect of bis-donors in the stabilization of heterodiatomic SiC compounds. Our calculations indicate that a typical bonding description of the SiC(D)2 compounds should be represented by a combination of a classical double bond between C-D with significant donor-acceptor interaction in Si-D, i.e., D → Si═C═D. The SiC(D)2 systems are found to be less stable than the corresponding dicarbon compounds C2(D)2, but they show significant stabilization compared to the corresponding disilicon systems Si2(D)2.

Reagent for Introducing Base-Stabilized Phosphorus Atoms into Organic and Inorganic Compounds.

The cyclic alkyl(amino) carbene (cAAC) stabilized monoanionic phosphorus atom in the form of lithium phosphinidene [cAACPLi(THF)2]2 (1) has been isolated as a molecular species and characterized by single crystal X-ray structure analysis. Furthermore, the structure and bonding of compound 1 has been investigated by theoretical methods. The utilization of the lithium phosphinidene as a phosphorus transfer reagent for a wide range of organic and inorganic substrates has been investigated. Herein, we report on the preparation of fascinating compounds containing P-C, P-Si, P-Ge, and P-P bonds using a single step with a base-stabilized phosphorus atom.

Mechanistic Exploration of the Transmetalation and Reductive Elimination Events Involving PdIV -Abnormal NHC Complexes in Suzuki-Miyaura Coupling Reactions: A DFT Study.

A comprehensive DFT (M06-L-D3(SMD)/BS2//M06-L/BS1 level) investigation has been carried out to explore in detail the mechanism of the transmetalation and reductive elimination reactions of abnormal N-heterocyclic carbene (aNHC) palladium(IV) complexes within the framework of Suzuki-Miyaura cross-coupling reactions. Emphasis was placed on the role of base and the effect of countercations on the critical transmetalation and reductive elimination events involving palladium(IV) complexes. Of the two competing roles of the base, the route involving boronate formation followed by halide exchange prevails over that of direct halide exchange for the intermediates [PdIV (aNHC)(OMe)2 Cl]- Na+ (pathway A), [PdIV (aNHC)(OMe)(Cl)2 ]- Na+ (pathway B), and [PdIV (aNHC)Cl3 ]- Na+ (pathway C) emanating from the oxidative addition reaction. The results of the calculations are in accordance with our previous theoretical findings of favorable energetics for palladium intermediates incorporating two coordinated methoxy groups. The negative role played by the countercation in the transmetalation step is mainly due to the overstabilization of the pre-transmetalation intermediate, which is in line with experimental kinetic results. The anionic complexes exhibit greater affinity for the transmetalation and reductive elimination reactions than the neutral variants.

Computational Investigation of Carbene-Phosphinidenes: Correlation between 31P Chemical Shifts and Bonding Features to Estimate the π-Backdonation of Carbenes.

Detailed investigations of the electronic structure and bonding scenario in different carbene-phosphinidenes have been presented using state-of-the-art computational methods (BP86/def2-TZVPP//BP86/def2-SVP). We have endeavored to find the correlation of the calculated 31P chemical shifts with different bonding parameters of compounds to access the relative π-acceptor strengths of the carbenes. 31P chemical shifts exhibit a weak correlation with σ-polarizations of Ccarb-P bonds toward phosphorus; however excellent correlations are obtained in the case of π-polarizations of Ccarb-P bonds toward the carbene carbon (Ccarb) and NPA charges on phosphorus atoms. 31P chemical shifts also show excellent correlations with the electron densities and energy densities of Ccarb-P bonds at BCPs, as suggested by QTAIM calculations. Moreover, EDA-NOCV analysis is implemented to gain brief insight into the bonding scenario in this class of compounds. Good correlation exists between the interaction energies between the carbene and PPh fragments and 31P chemical shifts. Additionally, we have investigated the correlations of calculated 31P chemical shifts with different bonding parameters of the corresponding free carbenes. The bonding scenario in different carbene-substituted phosphinidenes is also explored to see how the bonding situation depends on various substituents on phosphinidenes. The other substituted carbene-phosphinidenes show correlations similar to those of carbene-phenylphosphinidenes.

Silanylidene and Germanylidene Anions: Valence-Isoelectronic Species to the Well-Studied Phosphinidene.

The reduction of TipMCl3 (Tip=2,4,6-triisopropylphenyl) (M=Si, Ge) with KC8 in the presence of cyclic alkyl(amino) carbene (cAAC) afforded the acyclic silanylidene and germanylidene anions in the form of potassium salt [K(cAAC)MTip]2 (M=Si (1); Ge (2)). The silanylidene and germanylidene anions are valence-isoelectronic to the well-studied phosphinidene and are a new class of acyclic anions of Group 14. Compounds 1 and 2 were isolated and well characterized by NMR and single-crystal X-ray structure analysis. Furthermore, the structure and bonding of compounds 1 and 2 was investigated by computational methods.

Two Structurally Characterized Conformational Isomers with Different C-P Bonds.

The cyclic alkyl(amino) carbene (cAAC) bonded chlorophosphinidene (cAAC)P-Cl (2/2') was isolated from the direct reaction between cAAC and phosphorus trichloride (PCl3 ). Compound 2/2' has been characterized by NMR spectroscopy and mass spectrometry. 31 P NMR investigations [δ≈160 ppm (major) and δ≈130 ppm (minor)] reveal that there are two different P environments of the P-Cl unit. X-ray single-crystal determination suggests a co-crystallization of two conformational isomers of (cAAC)P-Cl (2/2'); the major compound possessing a cAAC-PCl unit with CcAAC -P 1.75 Å. This C-P bond length is very close to that of (NHC)2 P2 [NHC=N-heterocyclic carbene]. The residual density can be interpreted as a conformational isomer with a shorter CcAAC -P bond similar to a non-conjugated phosphaalkene [R-P=CR2 ]. Our study shows an unprecedented example of two conformational isomers with different Ccarbene -element bonds. Additionally, Br (3c/3c'), I (4c/4c'), and H (5c/5c') analogues [(Me2 -cAAC)P-X; X=Br (3), I (4), H (5)] of 2c/2c'[(Me2 -cAAC)P-Cl] were also synthesized and characterized by NMR spectroscopy suggesting similar equilibrium in solution. The unique property of cAAC and the required electronegativity of the X (X=Cl, Br, I, and H) atom play a crucial role for the existence of the two isomers which were further studied by theoretical calculations.

DFT Study on C-F Bond Activation by Group 14 Dialkylamino Metalylenes: A Competition between Oxidative Additions versus Substitution Reactions.

The C-F bond activation of pentafluoropyridine (PFP) by group 14 dialkylamino metalylenes has been studied employing DFT calculations. Emphasis is placed on the group 14 central atom (M = SiII, GeII, and SnII) and substituents (-NMe2, -NiPr2, -Cl, -NH2, and -PH2) dependent switching of oxidative addition to the metathesis/substitution reaction route, using state-of-the-art theoretical methods (M062X/def2-QZVP(SMD)//M062X/def2-TZVP) to provide a systematic classification of the individual mode of reactions. Moreover, an energy decomposition analysis (EDA) is implemented to get a brief insight into the physical factors that control the activation barriers originating via the different mode of reactions, viz., oxidative addition and metathesis routes. The key finding is that the distortion of PFP is the principal guiding factor in the oxidative addition reaction, while distortions imposed on both the PFP and metalylenes are inevitable toward the origin of the metathesis reaction barrier. The preferable oxidative addition reaction over metathesis of substituted silylenes can be explained on the basis of electron concentration and the HOMO-LUMO gap between the reacting substrates. However, the dramatic switch between oxidative addition and metathesis reaction in substituted germylenes depends on both the electronic and steric nature of the substituents. Similar observations are also noted for the reactivity of substituted stannylenes.