New Approach for Determining the Conformational Features of Pseudorotating Ring Molecules Utilizing Calculated and Measured NMR Spin−Spin Coupling Constants

A new method is developed to determine the most stable conformations of puckered rings by a comparison of measured and calculated SSCCs (DORCO:  determination of ring conformations). The DORCO method extensively uses the ring puckering coordinates to express the properties of a pseudorotating puckered ring. In the case of NMR spin−spin coupling constants (SSCCs) J, this leads to an extension of the Karplus relationship to puckered rings. For five-membered rings with puckering coordinates q and φ, the Karplus relationships adopt the form nJ(q,φ) or nJ(φ). It is shown in this paper that functions 3J(HCCH)(φ) calculated with coupled perturbed density functional theory for a parent molecule can also be used for derivatives of the parent molecule and help to determine their conformational probability distribution function ρ(φ). For this purpose, the DORCO procedure is developed to use functions nJ(φ) of the parent molecule in connection with measured SSCCs of the substituted compound. DORCO was tested for tetrahydrofuran and two of its derivatives. The most stable conformations were determined by an accuracy of 4% or better

Mechanism of the Diels−Alder Reaction Studied with the United Reaction Valley Approach: Mechanistic Differences between Symmetry-Allowed and Symmetry-Forbidden Reactions

The unified reaction valley approach (URVA) was used to investigate the mechanism of the reaction between ethene and 1,3-butadiene. The reaction valley was explored using different methods (Hartree−Fock, second-order Møller−Plesset perturbation theory, density functional theory (B3LYP), coupled cluster theory (CCSD(T)), and the basis sets 3-21G, 6-31G(d), and 6-311G(d,p). Results were analyzed by characterizing normal modes, the reaction path vector, and the curvature vector in terms of generalized adiabatic modes associated with internal parameters that are used to describe the reaction complex. The Diels−Alder reaction possesses three transition states (TS), where TS1 and TS3 correspond to bifurcation points of the reaction path, at which a Cs-symmetrical reaction complex converts into two C2-symmetrical reaction complexes. The activation enthalpy at 298 K is 23.5 kcal/mol according to calculations and corrected experimental data. It is determined by a symmetry-supported charge-transfer step, which is followed by a spin-recoupling and a bond formation step. Energy dissipation is strong in the exit channel. Mode selective rate enhancement seems to be not possible for symmetry-allowed reactions, which are characterized by a collective change of many internal coordinates of the reaction complex. Manipulation of the reaction barrier or the reaction mechanism (from concerted to nonconcerted) is only possible in the charge-transfer step. Contrary to opposite claims, aromaticity plays only a minor role for the TS energy

The Role of the HOOO^- Anion in the Ozonation of Alcohols: Large Differences in the Gas-Phase and in the Solution-Phase Mechanism

The mechanism of the ozonation of isopropyl alcohol was investigated for the gas and the solution phase using second-order many body perturbation theory and density functional theory (DFT) with the hybrid functional B3LYP and a 6-311++G(3df,3pd) basis set. A careful analysis of calculated energies (considering thermochemical corrections, solvation energies, BSSE corrections, the self-interaction error of DFT, etc.) reveals that the gas-phase mechanism of the reaction is dominated by radical or biradical intermediates while the solution-phase mechanism is characterized by hydride transfer and the formation of an intermediate ion pair that includes the HOOO- anion. The product distribution observed for the ozonation in acetone solution can be explained on the basis of the properties of the HOOO- anion. General conclusions for the ozonation of alcohols and the toxicity of ozone (inhaled or administered into the blood) can be drawn

Mechanism Investigation on Direct Conversion of Methane over a Mononuclear Rh-ZSM‑5 Catalyst: Multiple Roles of CO

In the present contribution, we investigated possible reaction mechanisms for the direct conversion of methane into methanol and acetic acid over a mononuclear rhodium species anchored on a zeolite support (Rh-ZSM-5) by density functional theory (DFT) calculations. To elucidate the role of CO, we systematically compared the reaction mechanisms in the absence/presence of CO. The most favored mechanism is shown to be via a CO-assisted oxygen activation, and the formation of the CO–O bond is found to be the rate-determining step. It is clearly shown from our calculations that the presence of CO will promote the formation of a more active Rh-oxo species, which can easily catalyze the conversion of methane so that the direct transformation of methane can be achieved under mild conditions. Apart from forming a stable catalytic precursor and promoting the formation of the active Rh-oxo species, CO can also be directly involved in the reaction, resulting in the formation of acetic acid

(<i>N</i>,<i>N</i>-Dimethylaminoxy)trifluorosilane: Strong, Dipole Moment Driven Changes in the Molecular Geometry Studied by Experiment and Theory in Solid, Gas, and Solution Phases

(N,N-Dimethylaminoxy)trifluorosilane, F3SiONMe2 (1), was prepared by the reaction of LiONMe2 with SiF4 in Me2O at −96 °C as a colorless, air-sensitive liquid, which was identified by gas-phase IR spectroscopy and NMR spectroscopy of the nuclei 1H, 13C, 15N, 17O, 19F, and 29Si. The gas-phase geometry of 1, as determined by electron diffraction analysis refined in Cs symmetry, is influenced by weak attractive interactions between Si and N:  Si···N 2.273(17) Å, Si−O−N 94.3(9)°, [Si−O 1.619(8) Å, N−O 1.479(7) Å, O−Si−Fin-plane 104.1(10)°, O−Si−Fout-of-plane 111.8(10)°]. X-ray diffraction analysis of 1 reveals that intramolecular Si···N interactions are much stronger in the solid state than in the gas phase:  Si···N 1.963(1) Å, Si−O−N 77.1(1)° [Si−O 1.639(1) Å, N−O 1.508(1) Å, O−Si−Fin-plane 102.5(1)°, O−Si−Fout-of-plane 118.0(1)° and 120.1(1)°]. Using measured NMR chemical shifts in C6D6 solution, the geometry of 1 in solution was determined with the NMR/ab initio/DFT-IGLO method to fall between that of the gas-phase geometry and the geometry in the solid state. MP2 and DFT calculations reveal that electrostatic interactions between 1 and the surrounding medium increase with the dielectric constant ε since mutual charge polarization enhances the molecular dipole moment from 4 to more than 6 D, which implies a compression of the Si−O−N angle and the Si···N distance. Since electrostatic attraction between N and Si supports these changes, the increase in molecular energy upon reduction of the Si···N distance is small and compensated by the gain of stabilizing intermolecular interactions. The analysis of the calculated electron density distribution shows that the main aspects of bonding in 1 are not changed in the solid state and that the Si···N attraction is not of covalent nature, but rather due to strong electrostatic and dipole interactions

Insights into the Mechanism of Metal-Catalyzed Transformation of Oxime Esters: Metal-Bound Radical Pathway vs Free Radical Pathway

Controlling of radical reactivity by binding a radical to the metal center is an elegant strategy to overcome the challenge that radical intermediates are “too reactive to be selective”. Yet, its application has seemingly been limited to a few strained-ring substrates, azide compounds, and diazo compounds. Meanwhile, first-row transition-metal-catalyzed (mainly, Fe, Ni, Cu) transformations of oxime esters have been reported recently in which the activation processes are assumed to follow free-radical mechanisms. In this work, we show by means of density functional theory calculations that the activation of oxime esters catalyzed by Fe­(II) and Cu­(I) catalysts more likely affords a metal-bound iminyl radical, rather than the presumed free iminyl radical, and the whole process follows a metal-bound radical mechanism. The as-formed metal-bound radical intermediates are an Fe­(III)-iminyl radical (Stotal = 2, SFe = 5/2, and Siminyl = −1/2) and a Cu­(II)-iminyl radical (Stotal = 0, SCu = 1/2, and Siminyl = −1/2). The discovery of such novel substrates affording metal-bound radical intermediates may facilitate the experimental design of metal-catalyzed asymmetric synthesis using oxime esters to achieve the desired enantioselectivity

(<i>N</i>,<i>N</i>-Dimethylaminoxy)trifluorosilane: Strong, Dipole Moment Driven Changes in the Molecular Geometry Studied by Experiment and Theory in Solid, Gas, and Solution Phases

(N,N-Dimethylaminoxy)trifluorosilane, F3SiONMe2 (1), was prepared by the reaction of LiONMe2 with SiF4 in Me2O at −96 °C as a colorless, air-sensitive liquid, which was identified by gas-phase IR spectroscopy and NMR spectroscopy of the nuclei 1H, 13C, 15N, 17O, 19F, and 29Si. The gas-phase geometry of 1, as determined by electron diffraction analysis refined in Cs symmetry, is influenced by weak attractive interactions between Si and N:  Si···N 2.273(17) Å, Si−O−N 94.3(9)°, [Si−O 1.619(8) Å, N−O 1.479(7) Å, O−Si−Fin-plane 104.1(10)°, O−Si−Fout-of-plane 111.8(10)°]. X-ray diffraction analysis of 1 reveals that intramolecular Si···N interactions are much stronger in the solid state than in the gas phase:  Si···N 1.963(1) Å, Si−O−N 77.1(1)° [Si−O 1.639(1) Å, N−O 1.508(1) Å, O−Si−Fin-plane 102.5(1)°, O−Si−Fout-of-plane 118.0(1)° and 120.1(1)°]. Using measured NMR chemical shifts in C6D6 solution, the geometry of 1 in solution was determined with the NMR/ab initio/DFT-IGLO method to fall between that of the gas-phase geometry and the geometry in the solid state. MP2 and DFT calculations reveal that electrostatic interactions between 1 and the surrounding medium increase with the dielectric constant ε since mutual charge polarization enhances the molecular dipole moment from 4 to more than 6 D, which implies a compression of the Si−O−N angle and the Si···N distance. Since electrostatic attraction between N and Si supports these changes, the increase in molecular energy upon reduction of the Si···N distance is small and compensated by the gain of stabilizing intermolecular interactions. The analysis of the calculated electron density distribution shows that the main aspects of bonding in 1 are not changed in the solid state and that the Si···N attraction is not of covalent nature, but rather due to strong electrostatic and dipole interactions

Table_1_Chemoselectivity in Gold(I)-Catalyzed Propargyl Ester Reactions: Insights From DFT Calculations.DOCX

Au-catalyzed propargyl ester reactions have been investigated by a comprehensive density functional theory (DFT) study. Our calculations explain the experimental observed chemoselectivity of Au-catalyzed propargyl ester reactions very well by considering all possible pathways both in the absence and presence of 1,2,3-triazole (TA). The “X-factor” of TA is disclosed to have triple effects on this reaction. First of all, it can stabilize and prevent rapid decomposition of the Au catalyst. Secondly, the existence of TA promotes the nucleophilic attack and alters the chemoselectivity of this reaction. Moreover, TA acts as a “relay” to promote the proton transfer.</p

Elucidating Structures of Complex Organic Compounds Using a Machine Learning Model Based on the ¹³C NMR Chemical Shifts

We present a protocol that combines the support vector machine (SVM) model with accurate 13C chemical shift calculations at the xOPBE/6-311+G­(2d,p) level of theory, denoted as SVM-M (i.e., SVM for magnetic property). We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence. Of particular significance is that, by utilizing the dual role of the decision values in SVM, the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue (i.e., “is a given structure correct or incorrect?”) and the comparison-based problem (i.e., “which structure is more likely to be correct or wrong among several candidate structures?”). A significantly high success rate has been reached (i.e., ∼100% on a set of 760 sample molecules with 15928 13C chemical shifts), which makes the SVM-M protocol a powerful tool for routine applications in structural and stereochemical assignments, as well as in detecting mis-assignments, for complex organic compounds, including natural products

Elucidating Structures of Complex Organic Compounds Using a Machine Learning Model Based on the ¹³C NMR Chemical Shifts

We present a protocol that combines the support vector machine (SVM) model with accurate 13C chemical shift calculations at the xOPBE/6-311+G­(2d,p) level of theory, denoted as SVM-M (i.e., SVM for magnetic property). We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence. Of particular significance is that, by utilizing the dual role of the decision values in SVM, the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue (i.e., “is a given structure correct or incorrect?”) and the comparison-based problem (i.e., “which structure is more likely to be correct or wrong among several candidate structures?”). A significantly high success rate has been reached (i.e., ∼100% on a set of 760 sample molecules with 15928 13C chemical shifts), which makes the SVM-M protocol a powerful tool for routine applications in structural and stereochemical assignments, as well as in detecting mis-assignments, for complex organic compounds, including natural products