Mechanism and Origins of Ligand-Controlled Selectivities in [Ni(NHC)]-Catalyzed Intramolecular (5 + 2) Cycloadditions and Homo-Ene Reactions: A Theoretical Study

The mechanism and origins of selectivities in [Ni­(NHC)]-catalyzed intramolecular (5 + 2) cycloadditions and homo-ene reactions of vinylcyclopropanes (VCPs) and alkynes have been studied using density functional theory. The preferred mechanism involves oxidative alkyne–alkene cyclization to form a metallacyclopentene intermediate, in contrast to a cyclopropane cleavage pathway in the reaction with Rh­(I) catalysts. The selectivity between the (5 + 2) and homo-ene products is determined in the subsequent competing reductive elimination and β-hydride elimination steps. Two similar-sized N-heterocyclic carbene (NHC) ligands, SIPr and ItBu, yielded reversed product selectivity, favoring the (5 + 2) and homo-ene products respectively. This is attributed to the anisotropic steric environment of these NHC ligands, which positions the bulky substituents on the ligand toward different directions and leads to distinct steric control in the reductive elimination and β-hydride elimination transition states

Entropic Path Sampling: Computational Protocol to Evaluate Entropic Profile along a Reaction Path

Fleeting intermediates constitute dynamically stepwise mechanisms. They have been characterized in molecular dynamics trajectories, but whether these intermediates form a free energy minimum to become entropic intermediates remains elusively defined. We developed a computational protocol known as entropic path sampling to evaluate the entropic variation of reacting species along a reaction path based on an ensemble of trajectories. Using cyclopentadiene dimerization as a model reaction, we observed an entropy maximum along the reaction path which originates from an enhanced conformational flexibility as the reacting species enter into a flat energy region. As the reacting species further approach product formation, unfavorable entropic restriction fails to offset the potential energy drop, resulting in no free energy minimum along the post-TS pathway. Our results show that cyclopentadiene dimerization involves an entropy maximum that leads to dynamic intermediates with elongated lifetimes, but the reaction does not involve entropic intermediates

Mechanisms and Origins of Switchable Chemoselectivity of Ni-Catalyzed C(aryl)–O and C(acyl)–O Activation of Aryl Esters with Phosphine Ligands

Many experiments have shown that nickel with monodentate phosphine ligands favors the C­(aryl)–O activation over the C­(acyl)–O activation for aryl esters. However, Itami and co-workers recently discovered that nickel with bidentate phosphine ligands can selectively activate the C­(acyl)–O bond of aryl esters of aromatic carboxylic acids. The chemoselectivity with bidentate phosphine ligands can be switched back to C­(aryl)–O activation when aryl pivalates are employed. To understand the mechanisms and origins of this switchable chemoselectivity, density functional theory (DFT) calculations have been conducted. For aryl esters, nickel with bidentate phosphine ligands cleaves C­(acyl)–O and C­(aryl)–O bonds via three-centered transition states. The C­(acyl)–O activation is more favorable due to the lower bond dissociation energy (BDE) of C­(acyl)–O bond, which translates into a lower transition-state distortion energy. However, when monodentate phosphine ligands are used, a vacant coordination site on nickel creates an extra Ni–O bond in the five-centered C­(aryl)–O cleavage transition state. The additional interaction energy between the catalyst and substrate makes C­(aryl)–O activation favorable. In the case of aryl pivalates, nickel with bidentate phosphine ligands still favors the C­(acyl)–O activation over the C­(aryl)–O activation at the cleavage step. However, the subsequent decarbonylation generates a very unstable <i>t</i>Bu-Ni­(II) intermediate, and this unfavorable step greatly increases the overall barrier for generating the C­(acyl)–O activation products. Instead, the subsequent C–H activation of azoles and C–C coupling in the C­(aryl)–O activation pathway are much easier, leading to the observed C­(aryl)–O activation products

Stepwise versus Concerted Reductive Elimination Mechanisms in the Carbon–Iodide Bond Formation of (DPEphos)RhMeI₂ Complex

Reductive elimination is the key bond formation process of organometallic reactions. Goldberg and co-workers recently revealed an unprecedented competition of parallel stepwise reductive elimination pathways for the carbon–iodide bond formation of (DPEphos)­RhMeI2 complex. To understand the controlling factors that differentiate the concerted and stepwise pathways, we performed density functional theory (DFT) calculations to elucidate the mechanistic details. The competing stepwise pathways were identified as the anionic and zwitterionic stepwise pathways. The anionic pathway involves the direct SN2 attack of the external iodide anion to the methyl group, leading to the observed carbon–iodide bond formation. Alternatively, heterolytic Rh–I bond cleavage generates the cationic (DPEphos)­RhMeI+ intermediate, and the subsequent SN2 attack of the iodide anion to the methyl group occurs via the zwitterionic transition state. In comparison with the stepwise reductive elimination pathways, the classic concerted pathways require significantly higher barriers. This is due to the energy penalty associated with the orientation change of the methyl group during the classic three-centered reductive elimination. The energy required for this orientation change is highly related to the hybrization of carbon; thus, the selectivity for the stepwise reductive elimination pathways can be switched if the C­(sp2) or C­(sp) group participates in the carbon–iodide bond formation

Mechanism and Origins of Selectivity in Ru(II)-Catalyzed Intramolecular (5+2) Cycloadditions and Ene Reactions of Vinylcyclopropanes and Alkynes from Density Functional Theory

The mechanism, solvent effects, and origins of selectivities in Ru­(II)-catalyzed intramolecular (5+2) cycloaddition and ene reaction of vinylcyclopropanes (VCPs) and alkynes have been studied using density functional theory. B3LYP/6-31G­(d)/LANL2DZ optimized structures were further evaluated with the M06 functional, 6-311+G­(2d,p) and LANL2DZ basis sets, and the SMD solvent model. The favored mechanism involves an initial ene-yne oxidative cyclization to form a ruthenacyclopentene intermediate. This mechanism is different from that found earlier with rhodium catalysts. The subsequent β-hydride elimination and cyclopropane cleavage are competitive, determining the experimental selectivity. In <i>trans</i>-VCP, the cyclopropane cleavage is intrinsically favored and leads to the (5+2) cycloaddition product. Although the same intrinsic preferences occur with the <i>cis-</i>VCP, an unfavorable rotation is required in order to generate the <i>cis</i>-double bond in seven-membered ring product, which reverses the selectivity. Acetone solvent is found to facilitate the acetonitrile dissociation from the precatalyst, destabilizing the resting state of the catalyst and leading to a lower overall reaction barrier. In addition, the origins of diastereoselectivities when the allylic hydroxyl group is <i>trans</i> to the bridgehead hydrogen are found to be the electrostatic interactions. In the pathway that generates the favored diastereomer, the oxygen lone pairs from the substituent are closer to the cationic catalyst center and provide stabilizing electrostatic interactions. Similar pathways also determine the regioselectivities, that is, whether the more or less substituted C–C bond of cyclopropane is cleaved. In the <i>trans</i>-1,2-disubstitued cyclopropane substrate, the substituent from the cyclopropane is away from the reaction center in both pathways, and low regioselectivity is found. In contrast, the cleavage of the more substituted C–C bond of the <i>cis</i>-1,2-disubstituted cyclopropane has steric repulsions from the substituent, and thus higher regioselectivity is found

Benchmark Study of Density Functional Theory Methods in Geometry Optimization of Transition Metal–Dinitrogen Complexes

The current benchmark study is focused on determining the most precise theoretical method for optimizing the geometry of transition metal–dinitrogen complexes. To accomplish this goal, seven density functional (DF) methods from five distinct classes of density functional theory (DFT) have been selected, including B3LYP-D3(BJ), BP86-D3(BJ), PBE0-D3(BJ), ωB97X-D, M06, M06-L, and TPSSh-D3(BJ). These DFs will be utilized with the Karlsruhe basis set (def2-SVP). To carry out this benchmark study, a total of forty-two structurally diverse transition metal–dinitrogen compounds with experimentally known X-ray data have been selected from the Cambridge Crystallographic Data Centre (CCDC). Based on a comparison of the theoretical data with experimental values (X-ray) of the selected transition metal–dinitrogen compounds, statistical parameters such as root-mean-square deviation (RMSD) and N–N and M–N bond lengths are obtained to evaluate the performance of the seven chosen DFs. According to the obtained results, among all DFT methods used in the study, Minnesota functionals (M06 and M06-L) and TPSSh-D3(BJ) show good performance, with lower RMSD values. This suggests that these three methods are the most reliable for optimizing the geometry of transition metal–dinitrogen complexes. Based on the absolute errors of the N–N and M–N bond lengths relative to the X-ray data, further analysis is conducted, and it is determined that M06-L is the best functional for optimizing the geometry of transition metal–dinitrogen compounds. Additionally, the influence of using a high-level basis set (def2-TZVP) compared to def2-SVP on the calculated RMSD among the seven chosen methods is found to be negligible

Highly Chemoselective, Transition-Metal-Free Transamidation of Unactivated Amides and Direct Amidation of Alkyl Esters by N–C/O–C Cleavage

The amide bond is one of the most fundamental functional groups in chemistry and biology and plays a central role in numerous processes harnessed to streamline the synthesis of key pharmaceutical and industrial molecules. Although the synthesis of amides is one of the most frequently performed reactions by academic and industrial scientists, the direct transamidation of tertiary amides is challenging due to unfavorable kinetic and thermodynamic contributions of the process. Herein, we report the first general, mild, and highly chemoselective method for transamidation of unactivated tertiary amides by a direct acyl N–C bond cleavage with non-nucleophilic amines. This operationally simple method is performed in the absence of transition metals and operates under unusually mild reaction conditions. In this context, we further describe the direct amidation of abundant alkyl esters to afford amide bonds with exquisite selectivity by acyl C–O bond cleavage. The utility of this process is showcased by a broad scope of the method, including various sensitive functional groups, late-stage modification, and the synthesis of drug molecules (>80 examples). Remarkable selectivity toward different functional groups and within different amide and ester electrophiles that is not feasible using existing methods was observed. Extensive experimental and computational studies were conducted to provide insight into the mechanism and the origins of high selectivity. We further present a series of guidelines to predict the reactivity of amides and esters in the synthesis of valuable amide bonds by this user-friendly process. In light of the importance of the amide bond in organic synthesis and major practical advantages of this method, the study opens up new opportunities in the synthesis of pivotal amide bonds in a broad range of chemical contexts

How Tethers Control the Chemo- and Regioselectivities of Intramolecular Cycloadditions between Aryl-1-aza-2-azoniaallenes and Alkenes

Cationic 1-aza-2-azoniaallenes react intermolecularly with terminal alkenes to give 1,5-substituted (3 + 2)-cycloadducts, but intramolecular reactions lead to either 1,5- or 1,4-substituted (3 + 2)-cycloadducts or (4 + 2)-cycloadducts, depending on the tether length. DFT calculations and distortion/interaction analyses show that the (CH₂)₃ tether prevents the reacting partners from aligning efficiently to give 1,5-substituted (3 + 2)-cycloadducts, and the 1,4-regioselectivity dominates. With the (CH₂)₂ tether, the (3 + 2) cycloaddition is disfavored due to the forming four-membered ring in the transition state, and the (4 + 2) cycloaddition prevails

How Doped MoS₂ Breaks Transition-Metal Scaling Relations for CO₂ Electrochemical Reduction

Linear scaling relationships between the adsorption energies of CO₂ reduction intermediates pose a fundamental limitation to the catalytic efficiency of transition-metal catalysts. Significant improvements in CO₂ reduction activity beyond transition metals require the stabilization of key intermediates, COOH* and CHO* or COH*, independent of CO*. Using density functional theory (DFT) calculations, we show that the doped sulfur edge of MoS₂ satisfies this requirement by binding CO* significantly weaker than COOH*, CHO*, and COH*, relative to transition-metal surfaces. The structural basis for the scaling of doped sulfur edge of MoS₂ is due to CO* binding on the metallic site (doping metal) and COOH*, CHO*, and COH* on the covalent site (sulfur). Linear scaling relations still exist if all the intermediates bind to the same site, but the combined effect of the two binding sites results in an overall deviation from transition-metal scaling lines. This principle can be applied to other metal/<i>p</i>-block materials. We rationalize the weak binding of CO* on the sulfur site with distortion/interaction and charge density difference analyses