Chao-Xian Yan

Insights into the Diels–Alder Reaction between 3-Vinylindoles and Methyleneindolinone without and with the Assistance of Hydrogen-Bonding Catalyst Bisthiourea: Mechanism, Origin of Stereoselectivity, and Role of Catalyst

The Diels-Alder reaction between 3-vinylindoles and methyleneindolinone can proceed both under catalyst-free conditions and with bisthiourea as the catalyst. The reaction with bisthiourea is much faster and results in higher stereoselectivity of the product. The reaction mechanism, origin of stereoselectivity, and role of the catalyst were elaborated based on quantum mechanical calculations and theoretical methods of reactivity indices, NCI, QTAIM, and distortion/interaction models. In the uncatalyzed reaction, the two C-C bonds that are formed undergo conversion from noncovalent to covalent bonding via a concerted asynchronous mechanism. The weak intermolecular interactions formed in the transition state play important roles. The difference between the interaction and distortion energies is responsible for the stereoselectivity. In the catalyzed reaction, bisthiourea induces both the diene and dienophile to approach it via weak intermolecular interactions, which greatly lowers the energy barrier of the reaction and leads to the product with excellent stereoselectivity. The possible pathways of this reaction were explored, which suggested that the formation of the two C-C bonds goes through either a stepwise or concerted asynchronous mechanism. These results detail the reaction mechanism and shed light on both the significant role of the bisthiourea catalyst and the origin of stereoselectivity for this type of Diels-Alder reaction and related ones.

Cooperative halogen bonds in V-shaped H3N·X1X2·X3Y (X1, X2, X3 = Cl and Br; Y = F, Cl and Br) complexes

A series of V-shaped molecular complexes formed by NH3, X1X2 and X3Y (X1, X2, X3 = Cl, Br; Y = F, Cl, Br) molecules via two halogen bonds (i.e., N⋯X1 and X2⋯X3 interactions) have been investigated at the MP2/aug-cc-pVTZ level of theory to obtain their optimized geometries, stretching modes and interaction energies. Molecular electrostatic potential was used to illustrate how X1 and X2 act as the halogen bond donor and acceptor in N⋯X1 and X2⋯X3 interactions, respectively. The evaluation of the binding distances, interaction energies and the electron density at the bond critical points of the halogen bonds reveals the existence of cooperativity between the two halogen bonds. Subsequently, the concepts of pair interaction and pairwise non-additive contributions to the total interaction energy, and the cooperativity factor were further employed to assess the cooperativity. The formation mechanisms of these complexes were analyzed based on the contour maps of the Laplacian (∇2ρ) of electron density. Energy decomposition analysis suggests that electrostatic force is the main net contribution to the stability of these complexes. The work would provide valuable insights into the design of related halogen-bonded complexes.

Mechanism of selective C–H cyanation of 2-phenylpyridine with benzyl nitrile catalyzed by CuBr: a DFT investigation

The mechanism of selective C–H cyanation of 2-phenylpyridine catalyzed by CuBr was investigated using the DFT method at the B3LYP/6-31+G(d,p) level, and the integral equation formalism polarized continuum model (IEFPCM) was applied to simulate the solvent effect. The computational results suggested that 2-phenylacetonitrile can convert into benzoyl cyanide under O2 conditions via two paths (a and b), and also, 2-phenylacetonitrile can first react with the O2− anion to yield 2-hydroxy-2-phenylacetonitrile, and then 2-hydroxy-2-phenylacetonitrile goes through oxidative dehydrogenation to yield benzoyl cyanide via four different paths (c, d, e and f). The other part reaction of the conversion of 2-phenylpyridine to 2-(pyridin-2-yl)-benzonitrile catalyzed by CuBr can go through three paths (g, h and i) which involve the coordination of CN− and the N atom of 2-phenylpyridine with Cu cations, and then the processes of addition and oxydehydrogenation reactions lead to the final product 2-(pyridin-2-yl)benzonitrile. In addition, another path (j) without the participation of CuBr could also occur. The results could provide valuable insights into these types of interactions and related ones.

Linear σ-hole⋯CO⋯σ-hole intermolecular interactions between carbon monoxide and dihalogen molecules XY (X, Y = Cl, Br)

Carbon monoxide can interact with two dihalogen molecules XY (X, Y=Cl, Br) in the form of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complex, and their nature and characteristics were investigated at MP2/aug-cc-pVDZ level without and with counterpoise method, together with single point calculations at CCSD(T)/aug-cc-pVDZ level. The optimized geometries, stretching modes and interaction energies of a series of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complexes were obtained and discussed. The cooperativity in these complexes was evaluated. EDA analyses reveal that the electrostatic interaction is the dominant net driving force in each trimer, but the contributions of other interactions like exchange, dispersion and polarization interactions are also important. QTAIM and NCI analyses confirm the existence of attractive halogen-bonding interactions. Additionally, EDDMF analysis was employed for the component dimers of these trimers, which indicates that the formation of halogen-bonding interactions is closely related to the charge shift and the rearrangement of electronic density in the formation of these complexes. The results would provide valuable insight into for these linear halogen bonds.

Quantitative relationships between bond lengths, stretching vibrational frequencies, bond force constants, and bond orders in the hydrogen-bonded complexes involving hydrogen halides

To uncover the correlation between the bond length change and the corresponding stretching frequency shift of the proton donor D–H upon hydrogen bond formation, a series of hydrogen-bonded complexes involving HF and HCl which exhibit the characteristics of red-shifted hydrogen bond were investigated at the MP2/aug-cc-pVTZ, M062X/aug-cc-pVTZ, and B3LYP/aug-cc-pVTZ(GD3) levels of theory with CP optimizations. A statistical analysis of these complexes leads to the quantitative illustrations of the relations between bond length and stretching vibrational frequency, between bond length and bond force constant, between stretching vibrational frequency and bond force constant, between bond length and bond order for hydrohalides in a mathematical way, which would provide valuable insights into the explanation of the geometrical and spectroscopic behaviors during hydrogen bond formation.

Chiral bisoxazoline catalyzed decarboxylative aldol reactions between β-carbonyl acids and trifluoroacetaldehyde hemiacetals as well as trifluoroacetaldehyde: the mechanism, the origin of enantioselectivity and the role of a catalyst

Chiral bisoxazoline can catalyze the decarboxylative aldol reactions between β-carbonyl acids and trifluoroacetaldehyde hemiacetals as well as trifluoroacetaldehyde but with quite different enantioselectivities, in which the reaction involving trifluoroacetaldehyde hemiacetal results in excellent enantioselectivity (95% ee) while that involving trifluoroacetaldehyde results in poor enantioselectivity (28% ee). To uncover their differences, quantum mechanical calculations together with theoretical methods of global reactivity indexes, QTAIM, NCI and distortion/interaction models were applied to these two reactions; the reaction mechanism, the origin of enantioselectivity and the role of bisoxazoline were investigated in detail. For the reaction with 95% ee, it undergoes the processes of decomposition of trifluoroacetaldehyde hemiacetal, nucleophilic addition, decarboxylation and enol–keto tautomerization of the product, and the nucleophilic addition is the rate- and stereo-determining step. Both the distortion energy and weak intermolecular interactions are responsible for the enantioselectivity. For the reaction with 28% ee, it goes through the processes of nucleophilic addition, decarboxylation and enol–keto tautomerization of the product. Chiral bisoxazoline plays a crucial role in increasing the nucleophilicity of β-carbonyl acid in the reaction leading to 95% ee, while such a role is not observed in the reaction resulting in 28% ee. The calculated ee values are in good agreement with the experimental results. The results shown here will provide valuable insights into the understanding of these types of reactions, the design of highly efficient organocatalysts, and related asymmetric reactions.

Fenamic acid crystal with two asymmetric units (Z′ = 2): why Z′ = 2 rather than Z′ = 1

Two molecules with different conformations appear in the asymmetric unit of fenamic acid crystal (Z′ = 2). The two conformations have higher energies, and they dimerize via asymmetric O–H⋯O hydrogen bonds. For the predicted crystal (Z′ = 1), the symmetric O–H⋯O hydrogen bonds form between the lower energy conformers. Quantum mechanical calculations were carried out to elaborate the existence of higher energy conformers and their special arrangements. The asymmetric O–H⋯O hydrogen bonds in the crystal (Z′ = 2) are even stronger than the symmetric O–H⋯O hydrogen bonds in the predicted crystal (Z′ = 1), which is an important reason that the crystal with Z′ = 2 is observed. Additionally, intricate intermolecular interactions, that is, many adjacent molecules interacting with the substituted and unsubstituted benzene groups of higher energy conformers, also come into play, and these interactions cooperate and stabilize the conformers. A comparison of these intermolecular interactions in the crystal (Z′ = 2) with those in the predicted crystal (Z′ = 1) was made. The potential factors holding the two higher energy conformers together as a packing motif have been discussed in detail. We expect that the results could shed light on the understanding of the origin of the Z′ = 2 structure and other higher Z′ structures.