Cyclic vinyl p-tolyl sulfilimines as chiral dienophiles: theoretical study on the stereoselectivity, Lewis acid catalysis, and solvent effects in their Diels-Alder reactions

The theoretical study reported in the present work deals with chiral cyclic vinyl sulfilimines and their reactivity as dienophiles in [4 + 2] cycloaddition reactions, using B3LYP/6-31G(d)//AM1 and B3LYP/6-31G(d)//B3LYP/6-31G(d) model chemistries. Consideration of Lewis acid catalysis, illustrated by BF(3), decreases the activation energies of the cycloaddition process while the charge transfer from the diene to the sulfilimine is augmented. The [4 + 2] cycloaddition reactions of sulfilimines with both furan and cyclopentadiene occur in the gas phase with endo stereoselectivity, which is more pronounced with the latter diene. Endo-exo energy differences in the gas phase with the B3LYP/6-31+G(d)//B3LYP/6-31+G(d), B3LYP/6-31G(d)//B3LYP/6-31G(d), and B3LYP/6-31G(d)//AM1 model chemistries are almost the same. Solvent effects are responsible for the inversion of the stereoselectivity in the reactions of sulfilimines with furan because of the great difference in the dipole moments in endo and exo approaches.     

Intra- and intermolecular 1,3-dipolar cycloaddition of sugar ketonitrones with mono-, di-, and trisubstituted dipolarophiles

The 1,3-dipolar cycloaddition of sugar ketonitrones is a useful synthetic procedure to build up nitrogenated quaternary centers in terms of scope (substrate, dipolarophile, inter- and intramolecular versions), yield, and regio- and stereoselectivity. The hybrid ONIOM (B3LYP/6-31G(d):AM1) theoretical method followed by single-point energy calculations at the B3LYP/6-31G(d) level adequately perform to model this cycloaddition for the relatively large ketosugar precursors commonly used.     

Substituent Effects on Site Selectivity (C=C vs C=N) in Heterocumulene-Heterodiene [4 + 2] Cycloadditions: Density Functional and Semiempirical AM1 Molecular Orbital Calculations

The effect of substituents on the site selectivity (C=C vs C=N) in the [4 + 2] cycloaddition between heterocumulenes (ketene imines) 2a-g with heterodienes (acroleines 9a-n and 4-acylfuran-2,3-diones 1a-d) is treated by semiempirical AM1 molecular orbital and density functional calculations using Becke's three-parameter hybrid method (B3LYP/6-31G). For some reactions calculations were also done at the B3LYP/6-31+G level of theory. For reaction of the oxa 1,3-dienes with ketene imines unsubstituted at the terminal carbon invariably addition across the C=C heterocumulene double bond has a lower activation energy than addition across the C=N double bond. Substitution of methyl or especially phenyl groups at the ketene imine C-terminus leads to a reversal of the respective activation energies. Incorporation of the oxa 1,3-diene system into the heterocyclic dione 1 substantially enhances the reactivity ( approximately 10 kcal mol(-1) lower activation energies) as compared to similarly substituted acroleins. At the DFT level of theory all reactions are found to proceed via a concerted asynchronous mechanism.     

Ab initio and DFT studies on the mechanism of the 1,3-dipolar cycloaddition reaction between nitrone and sulfonylethene chloride

The molecular mechanism for the 1,3-dipolar cycloaddition of nitrone with sulfonylethene chlorides has been studied using ab initio and DFT methods at the HF, MP2 and B3LYP levels together with the 6-31G* basis set. Relative rates, stereo and regioselectivity, have been analysed and discussed. For this cycloaddition four reactive channels associated with the formation of two pairs of diastereoisomeric regioisomers have been characterized. Analysis of the geometries of the corresponding transition structures shows that the cycloaddition takes place along a concerted but asynchronous mechanism. Activation energies as asynchronicity are dependent on the computation level. Thus, while HF calculations gave large barriers, MP2 calculations tend to underestimate them. DFT calculations gave reasonable values. These 1,3-dipolar cycloadditions present an endo stereoselectivity while the meta regioselectivity depends on the computational level. Thus, while HF and DFT calculations predict meta path, in agreement with the experimental results, MP2 calculation predict ortho regioselectivity. The frontier molecular orbitals analysis shows that the reaction is controlled by the (HOMO_dipole–LUMO_{dipolarophile}) interaction in agreement with the charge transfer analysis carried out at the transition structures. Inclusion of diffuse functions at the B3LYP/6-31+G* level increases the energy barriers about 4 kcal/mol, giving a similar endo/meta selectivity. Solvent effects have been taken into account, by means of self-consistent reaction field.     

密度泛函方法研究气相胞嘧啶的互变异构化

By comparing the ready experimental results with the calculated results obtained at 7 basis sets and 3 theoretical levels, respectively, for the tautomeric form Cyt1 of cytosine, the relatively accurate B3LYP/6-311+G** theoretical method to study the tautomerism of cytosine was chosen. The ground-state structures of 8 tautomers of cytosine were fully optimized at B3LYP/6-311+G** level, and the tautomerism of 6 relatively stable tautomers of cytosine was studied. The frequency analysis was performed on all the optimized structures. For the ground state geometries, all the calculated frequencies are real; for the transition-state geometries, there is only one imaginary frequency for each structure. Detailed Intrinsic Reaction Coordination calculations were carried out to guarantee the optimized transition-state structures being connected to the related tautomers. All the energies given include the zero-point energy corrections. The theoretical results can give a reasonable interpretation for the experimental results.     

A cornucopia of cycloadducts: theoretical predictions of the mechanisms and products of the reactions of cyclopentadiene with cycloheptatriene

The potential cycloaddition reactions between cyclopentadiene and cycloheptatriene have been explored theoretically. B3LYP/6-31G was used to locate the transition states, intermediates, and products for concerted pathways and stepwise pathways passing through diradical intermediates. Interconversions of various cycloadducts through sigmatropic shifts were also explored. CASPT2/6-31G single point calculations were employed to obtain independent activation energy estimates. MM3 was also used to compute reaction energetics. Several bispericyclic cycloadditions in which two cycloadducts are linked by a sigmatropic shift have been identified. B3LYP predicts, in line with frontier molecular orbital predictions, that the [6+4] cycloaddition is the favored concerted pathway, but an alternative [4+2] pathway is very close in energy. By contrast, CASPT2 predicts that a [4+2] cycloaddition is the preferred pathway. B3LYP predicts that the lowest energy path to many of the cycloadducts will involve diradical intermediates, whereas CASPT2 predicts that each of the products of orbital symmetry allowed reactions will be reached most readily by closed shell processes-concerted cycloadditions and sigmatropic shift rearrangements of cycloadducts.     

Imidazo[1,2-a]pyrazine-3,6-diones derived from alpha-amino acids: a theoretical mechanistic study of their formation via pyrolysis and silica-catalyzed process

Imidazo[1,2-a]pyrazine-3,6-diones are unusual compounds composed of three alpha-amino acid fragments. These bicyclic amidines (BCAs) form under high temperatures or with the use of strong dehydrating reagents. We gave insight into the mechanisms of BCA formation via gas-phase pyrolytic and silica-catalyzed reactions of glycine (Gly) and alpha-aminoisobutyric acid (AIB) with related diketopiperazines (DKPs), using quantum chemical calculations. The entire process requires four steps: (1) O-acylation of DKP with free or silica-bonded amino acid, (2) acyl transfer from the oxygen to the nitrogen atom, (3) intramolecular condensation of the N-acyl DKP into a cyclol, and (4) elimination of water. To study step (1) at silica surface (modeled by H7Si8O12-OH cluster), we employed two-level ONIOM calculations (AM1:UFF, B3LYP/3-21G:UFF and B3LYP/6-31G(d):UFF); all gas-phase reactions were studied at the AM1, B3LYP/3-21G and B3LYP/6-31G(d) levels. The catalytic effect of silica was observed for both Gly and AIB: the activation energy in the O-acylation at the surface was lower by more than 9 kcal mol(-1) as compared to the gas-phase process. Contrary to the exothermic O-acylation, the gas-phase transfer reaction (step 2) was exothermic in both cases, but more favorable for Gly. The cyclocondensation of N-acylated DKPs into BCAs (steps 3 and 4) is endothermic for Gly and exothermic for AIB.     

苯并氧化呋咱稳定性和异构化的DFT和ab initio研究

运用B3LYP/6-31G(d)密度泛函理论（DFT）方法对苯并氧化呋咱、邻二亚硝基苯及其间的异构化反应进行了计算研究。结果表明,苯并氧化呋咱的分子总能量比邻二亚硝基苯的低;由苯并氧化呋咱异构为邻二亚硝基苯的正向反应活化能（Ea+=51.0kJ/mol）,与文献实测值（58.6kJ/mol）较接近,而其逆向反应活化能（Ea-=4.6kJ/mol）很小,从而揭示了苯并氧化呋咱比邻二亚硝基苯更稳定·此外,进行了HF/3-21G、HF/6-31G(d)和MP2/6-31G(d)//6-31G(d)水平下相应的计算,发现B3LYP-DFT的结果较abinitio为优。谐振动频率的B3LYP/6-31G(d)计算还支持了邻二亚硝基苯为苯并氧化呋咱“自-自”互变重排反应的中间体。     

哒嗪裂解反应机理的密度泛函理论研究

利用密度泛函理论(DFT)方法, 以哒嗪为煤的模型化合物, 在(U)B3LYP/6-31G(d,p)水平下计算了标题化合物的键布居数和键裂解能, 并对其热解机理进行了探讨. 在(U)B3LYP/6-311++G(d,p)水平下计算了热解过程中各物种的单点能, 并对总能量进行了校正. 结果表明, 标题物N-N键的布居数和裂解能均最小, 且各键裂解能随温度变化不大, 热解最终产物为HCN和乙炔, NH₃可能是HCN经过二次转换得到的. 采用过渡态理论计算了300~1900 K温度范围内热解的速率常数, 求得lnk与1/T的线性关系.     

吡啶-BH~3相互作用复合物的理论研究

对吡啶-BH~3复合物分别用MP2/6-31+G^*和B3LYP/6-31+G^*进行理论计算以预测该复合物的构型及解离能，得到四种构型，在MP2优化构型基础上作CCSD/6-31+G^*单点能量计算以验证MP2与B3LYP结果的可靠性，然后用B3LYP作振动频率分析，计算了各构型的垂直电离势，最后用更大基组作单点能量计算和自然键轨道(NBO)分析。结果表明，N-B直接相连的构型最稳定，其解离能为141.50kJ/mol,MP2和B3LYP对N-H接近的构型结果相关较大，另外两种构型稳定性介于二者之间，解离能分别为15.18kJ/mol,14.06kJ/mol(MP2/6-31+G^*)。     

Theoretical Study of Mechanism and Regioselectivity of 1,3-dipolar Cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] Nitrilimine with Dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate

The mechanism and regioselectivity of 1,3-dipolar cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] nitrilimine with dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate were investigated using activation energy calculations and density functional theory-based re-activity indexes. The reaction proceeds by an asynchronous concerted mechanism. The calculations are performed at the B3LYP/6-31G(d) level of theory and the obtained results are in agreement with experimental outcome.     

单重态二溴卡宾和甲醛环加成反应的量化研究

采用量子化学密度泛函理论,研究了单重态二溴卡宾和甲醛环加成反应的机理.在B3LYP/6-31G*基组水平上,优化得到了反应途径上反应物、过渡态、中间体和产物的几何构型;计算并考察了四种可能反应途径势能面上各驻点的构型参数、振动频率和能量;通过振动分析对过渡态和中间体构型进行了确认.计算结果表明,二溴卡宾和甲醛反应有四条反应通道,其中c反应通道(即0°-0°型)控制步骤的活化能仅为13.7 kJ·mol－1,反应容易进行.     

Transition structures of diastereoselective 1,3-dipolar cycloadditions of nitrile oxides to chiral homoallylic alcohols

Transition structures of the 1,3-dipolar cycloaddition of substituted nitrile oxides with chiral homoallylic alcohols were explored with density functional theory (B3LYP/6-311+G(d,p)+CPCM(dichloromethane)//B3LYP/6-31+G(d)). The diastereoselectivity observed in these reactions was explained. The anti product is favored in both the thermal and magnesium-mediated reactions. Selectivity is predicted to increase in the presence of magnesium, in agreement with experimental results. The energetics of the magnesium-mediated reaction are similar to those previously found for allylic alcohols. [structure: see text].     

A theoretical study of the structure and vibrations of 2,4,6-trinitrotolune

Theoretical calculations of the structure, internal rotations and vibrations of 2,4,6-trinitrotolune, TNT, in the gas phase were performed at the B3LYP/6-31G* and B3LYP/6-311+G** levels of theory. Two genuine energy minimum structures were found. In both structures the 4-nitro group is planar to the phenyl ring, while the 2,6-nitro groups are slightly out of plane with the phenyl ring due to steric interaction with the methyl group. The two structures are related by internal rotations of the methyl and 2, or 6-nitro group. The lowest energy route for interconversion between them is a concerted motion of the methyl group and 2 or 6 nitro group in a ‘cog wheel’ type of mechanism. The geometry of the low energy structure A is closest to that observed in the crystal structures of TNT, where all three nitro groups are out of plane with the phenyl ring. FTIR and Raman spectra of solid TNT and ¹³C, ¹⁵N enriched TNT are presented and assigned with the help of the B3LYP/6-311+G** calculations on A. The lower level B3LYP/6-31G* calculation fails to predict the correct vibrational coupling between the nitro and phenyl groups. The B3LYP/6-311+G** calculation gives a good prediction of the nitro vibrations and the isotopic shifts observed for TNT isotopomers.     

Theoretical investigation of enolborane addition to alpha-heteroatom-substituted aldehydes. Relevance of the Cornforth and polar Felkin-Anh models for asymmetric induction

The addition of enolborane nucleophiles to chiral alpha-heteroatom-substituted aldehydes (CH(3)CH(X)CHO, X = F, Cl, OMe, SMe, NMe(2), and PMe(2)) was investigated using density functional theory by means of B3LYP/6-31G(d) calculations, with particular emphasis on determining the relevance of the polar Felkin-Anh and Cornforth models for asymmetric induction in these reactions. The relative energy of the polar Felkin-Anh and Cornforth transition-state structures is found to depend on the nature of the alpha-heteroatom substituent, with electronegative substituents (F, OMe, Cl) favoring Cornforth structures, while less electronegative substituents (PMe(2), SMe, NMe(2)) favor polar Felkin-Anh structures. These transition-state preferences are correlated with the relative energy of the corresponding rotamer of the uncomplexed reactant aldehyde, indicating that the transition states are particularly sensitive to the conformation of the aldehyde. The proposed Nu --> sigma*(C-X) interaction that forms the basis of the polar Felkin-Anh model appears to be insignificant in reactions with enolborane nucleophiles. The calculated transition-state structures for the addition of E- and Z-enolborane nucleophiles to 2-methoxypropanal predict a diastereofacial selectivity that is in good agreement with the experimentally determined values.     

Theoretical Study on the Tautomerization Reaction of Formamide to Formamidic Acid Encapsulated in a Nano-sized Molecular Container

The hybrid calculations with ONIOM(B3LYP/6-31G*:AM1) method were carried out on the tautomerization reaction of formamide to formamidic acid in the microcontainer-encapsulated state. The free-state tautomerization process was also investigated with B3LYP/6-31G**//B3LYP/6-31G* method for the purpose of comparison. Bare tautomerization, H2O-assisted(single-H2O or multiple-H2O) and self-assisted mechanisms were all taken into consideration for the encapsulated state. The results show that only bare tautomerization and single-H2O catalysis mechanisms are possible to the encapsulated for-mamide tautomerization owing to the container's size confinement effect. Geometrical changes in the complexed container and guest molecules are discussed to deeply understand the complex's structural properties. The bare tautomerization barrier in the encapsulated state increases by 23.826 kJ/mol, ac-counting for 12% of the corresponding total energy barrier in the free state, and the increased values for the single-H2O catalysis process are 12.958 kJ/mol, accounting for 16% of the corresponding total energy barrier, respectively. This finding suggests that the encapsulation can make the tautomerization process slightly difficult.     

A computational study of the cycloaddition of thiobenzophenone S-methylide to thiobenzophenone

The cycloaddition of thiobenzophenone S-methylide to thiobenzophenone, an experimentally well-known reaction, was studied, using (U)HF/3-21G* for finding stationary points and (U)B3LYP/6-31G*//(U)HF/3-21G* single-point calculations for energies. Some optimizations were performed by (U)B3LYP/ 6-31G* to check the reliability of the calculations. The comparison of the concerted pathways and stepwise reactions via C,C-biradicals and C,S-zwitterions showed that the formation of a tetraphenyl-substituted C,C-biradical and its ring closure to 4,4,5,5-tetraphenyl-1,3-dithiolane constitutes the energetically most probable pathway of product formation, despite the fact that the regioisomeric 2,2,4,4-tetraphenyl-substituted product is more favorable by 17 kcal mol(-1). Model calculations on bond dissociation energies showed that (U)B3LYP with various basis sets overestimates radical stabilization, whereas CBS-QB3 closely reproduced experimental values. Results with the BLYP functional are similar to those with B3LYP. The consequences of the overestimation of radical stability for the cycloaddition mechanism involving biradicals are discussed. Thiobenzophenone S-methylide, if not captured by a dipolarophile, dimerizes to 2,2,3,3-tetraphenyl-1,4-dithiane. Calculation disclosed likewise a tetraphenyl-substituted C,C-biradical as intermediate.     

二氯亚甲基锗烯与乙烯环加成反应机理的理论研究

The mechanism of a cycloaddition reaction between singlet dichloromethylene germylene and ethylene has been investigated with B3LYP/6-31G＊ method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies for the involved conformations were calculated by CCSD（T）//B3LYP/6-31G＊ method. On the basis of the surface energy profile obtained with CCSD（T）// B3LYP/6-31G＊ method for the cycloaddition reaction between singlet dichloromethylene germylene and ethylene, it can be predicted that the dominant reaction pathway is that an intermediate INT1 is firstly formed between the two reactants through a barrier-free exothermic reaction of 61.7 kJ/mol, and the intermediate INT1 then isomerizes to an active four-membered ring product P2.1 via a transition state TS2, an intermediate INT2 and a transition state TS2.1, in which energy barriers are 57.7 and 42.2 kJ/mol, respectively.     

Semiempirical PM5 molecular orbital study on chlorophylls and bacteriochlorophylls: comparison of semiempirical, ab initio, and density functional results

The semiempirical PM5 method has been used to calculate fully optimized structures of magnesium-bacteriochlorin, magnesium-chlorin, magnesium-porphin, mesochlorophyll a, chlorophylls a, b, c(1), c(2), c(3), and d, and bacteriochlorophylls a, b, c, d, e, f, g, and h with all homologous structures. Hartree-Fock/6-31G* ab initio and density functional B3LYP/6-31G* methods were used to optimize structures of methyl chlorophyllide a, chlorophyll c(1), and methyl bacteriochlorophyllides a and c for comparison. Spectroscopic transition energies of the chromophores and their 1:1 or 1:2 solvent complexes were calculated with the Zindo/S CIS method. The self-consistent reaction field model was used to estimate solvent shifts. The PM5 calculations predict planar structure of the porphyrin ring and central position of the four coordinated magnesium atoms in all pigments studied, in accord with the experimental, ab initio, and density functional results, a significant improvement as compared to the older semiempirical PM3 approach. Only small differences in PM5 and B3LYP/6-31G* or Hartree-Fock/6-31G* minimum energy geometries of the reference molecules were observed. Calculations show that in 1:1 solvent complexes, where the magnesium atom is five coordinated, the magnesium atom is shifted out of the plane of the porphyrin ring towards the solvent molecule, while the hexa coordinated 1:2 complexes are again planar. The PM5 method gives atomic charges that are comparable with those obtained from the Hartree-Fock/6-31G* and B3LYP/6-31G* calculations. The single point ZINDO/S CIS calculations with PM5 minimum energy structure gave excellent correlations between calculated and experimental transition energies of the chlorophylls and bacteriochlorophylls studied. Such correlations may be used for prediction of transition energies of the chromophores in protein binding sites. Calculations also predict existence of dark electronic states below the main Soret absorption band in all chromophores studied. The results suggest that the semiempirical PM5 method is a fairly reliable and computationally efficient method in predicting molecular parameters of porphyrin-like molecules.     

Thioformaldehyde S-methylide and thioacetone S-methylide: an ab initio MO study of structure and cycloaddition reactivity

The mechanisms of cycloaddition of thioformaldehyde S-methylide and thioacetone S-methylide, as models for an alkyl-substituted ylide, to thioformaldehyde and thioacetone, as well as to ethene as a model for a C=C double bond have been studied by ab initio calculations. Restricted and unrestricted B3LYP/6-31G* calculations were performed for the geometries of ground states, transition structures, and intermediates. Although basis sets with more polarization functions were tested, the 6-31G* basis set was applied throughout. Single-point CASPT2 calculations are reported for analysis of the unsubstituted system. The stabilities of structures with high biradical character seem to be overestimated by DFT methods in comparison to CASPT2. The general trends of the results are independent of the level of theory. Thioformaldehyde adds to thioformaldehyde S-methylide without activation energy, and the activation energies for two-step biradical pathways to 1,3-dithiolane are low. C,S biradicals are more stable than C,C biradicals. The two-step cycloaddition is not competitive with the concerted cycloaddition. Methyl substitution in the 1,3-dipole and the dipolarophile does not change the mechanistic relationships. TSs for the concerted formation of the regioisomeric cycloadducts of thioacetone Smethylide and thioacetone were located. Concerted addition remains the preferred reaction. The reactivity of the C=S double bond is high relative to that of the C=C double bond.