Conformational control of flexible molecules: design and synthesis of novel chiral 1,5-diaza-cis-decalins

Control of the conformational equilibria of 1,5-diaza-cis-decalins, a new class of chiral diamine ligands, has been investigated. Chiral 2,6- and 3,7-substituted derivatives of 1,5-diaza-cis-decalins were designed to stabilize the conformational form needed to chelate a lithium. These derivatives were synthesized in optically pure form starting from 1,5-diaza-cis-decalin. Due to the rigid and conformationally well-defined nature of these compounds, the potential of these compounds as chiral diamine ligands was investigated. Asymmetric lithiation-substitution reactions of N-Boc-pyrrolidine and N,N-diisopropyl-o-ethylbenzamide were performed using these ligands and up to 60% ee was obtained. For the latter substrate, results spanning a range from 32% ee (R) to 60% ee (S) were obtained (Delta ee = 92%) with 1,5-diaza-cis-decalin ligands differing only in the location of two methyl substituents. Unlike many other diamines that have been employed in asymmetric lithiation-substitution reactions, the limited conformational flexibility of the 1,5-diaza-cis-decalins is analogous to (-)-sparteine such that these results may permit the construction of structure-activity relationships.     

Molecular modeling of ring-chain equilibria for the ring-opening cross-metathesis of cis,cis-1,5-dimethyl-cycloocta-1,5-diene with ethylene at T=298.15 K

The molecular modeling of ring-opening cross-metathesis of cis,cis-1,5-dimethyl-cycloocta-1,5-diene (1,5-DM-COD), cis,cis-1,6-dimethyl-cycloocta-1,5-diene (1,6-DM-COD) and cis,cis-cycloocta-1,5-diene (COD) with ethylene (ethenolysis) at T=298.15 K using the B3LYP/6-31G(d,p) level of theory reveals that ring-chain equilibrium constants are dependent on the nature of cyclic diene. The ring-chain equilibria for the ethenolysis of 1,5-DM-COD is completely shifted to the formation of monomeric 2-methyl-hexa-1,5-diene.     

1. 5-环辛二烯-3, 7-二炔(C~8H~4)结构和光谱性质的理论研究

采用量子化学从头算方法研究了1,5-环辛二烯-3,7-二炔(C~8H~4)的结构和光谱性质,根据等键反应分析和自然键轨道方法研究了它的稳定性、成键情况和共轭性。结果表明1,5-环辛二烯-3,7-二炔(C~8H~4)分子为平面刚性结构,可能稳定存在。分子中C≡C键与C=C键存在一定程度的共轭,可能具有芳香性。     

Density functional theory study of ring-chain equilibria for the cross-metathesis of cyclohexene and cis,cis-cycloocta-1,5-diene with functionalized olefins

The computational modeling of ring-chain equilibria for the ring-opening cross-metathesis of cyclohexene (CH) with 1,2-dicarbomethoxy-ethylene (DCE), 1,4-dicarbomethoxy-but-2-ene (DCB) and ethylene at T = 298.15 K using the B3LYP/6-31G(d,p) level of theory revealed that CH and ring-opened products equilibrium is shifted towards the thermodynamically stable six-membered ring. The calculations demonstrated that carbonyl-containing olefins can completely drive the equilibrium in the cross-metathesis with cis,cis-cycloocta-1,5-diene (COD) towards the ring-opened products.     

A Quantum Chemical Study of N14 Cluster

Ab initio molecular orbital theory and density functional theory have been employed to study N₁₄ cluster with low spin at the HF/6-31G*, B3LYP/6-31G*, B3PW91/6-31G*, BP86/6-31G*, and BHLYP/6-31G* levels of theory. Twelve isomers were studied, including one previously investigated cage molecule. The most stable isomer of N₁₄ is a C _2h -symmetric molecule that contains two separated five-membered nitrogen rings connected by a —N=N—N=N— bridge. The second, third, and fifth most stable isomers each have one five-membered nitrogen ring. The theoretical results suggest that the five-membered nitrogen ring gives rise to a particularly stable structural unit, and the more side chains that the five-membered nitrogen ring links with, the less stable the structure will become.     

Enantioselective oxidative biaryl coupling reactions catalyzed by 1,5-diazadecalin metal complexes

[reaction: see text]. Chiral 1,5-diaza-cis-decalins have been examined as ligands in the enantioselective oxidative biaryl coupling of substituted 2-naphthol derivatives. Under the optimal conditions employing a 1,5-diaza-cis-decalin copper(I) iodide complex with oxygen as the oxidant, rapid and highly selective couplings could be achieved (90-93% ee, 85% yield).     

Synthesis,Characterization and Theoretical Studies on a Thiocarbamide Derivative Containing Schiff Base Group

A thiocarbamide derivative containing Schiff base groups,1,5-bis[4-(dimethylamino)benzylidene]thiocarbonohydrazide,has been synthesized and characterized by elemental analysis,IR,1H NMR,UV and X-ray single-crystal diffraction.Density function theory(DFT) calculations at the B3LYP/6-31G* and PBE0/6-31G* levels for optimized geometries and electronic transition spectra have been performed.Comparative studies show that both B3LYP/6-31G* and PBE0/6-31G* methods can well reproduce the molecular structure,and the latter is more reliable than the former to simulate electronic spectra.NPA calculational results at the B3LYP/6-31G* level indicate the title compound to be a potential multidentate ligand to the metallic ions.Based on the vibrational analysis,thermodynamic properties at different temperatures have been obtained.     

A B3LYP study of the effects of phenyl substituents on 1,5-hydrogen shifts in 3-(Z)-1,3-pentadiene provides evidence against a chameleonic transition structure

The effects of one or two phenyl substituents on the activation enthalpy for a 1,5-hydrogen shift in 3-(Z)-1,3-pentadiene (1) and on the geometry of the transition structure (TS) have been investigated by B3LYP/6-31G calculations. The phenyl-substituent effects on the experimentally measured activation enthalpies are predicted to be sizable, spanning a range of nearly 10 kcal/mol. However, if differences between steric effects in the transoid isomers of the reactants are factored out by comparing the activation enthalpies in the cisoid conformers, the electronic components of the phenyl-substituent effects on both the barrier heights and the TS geometries are found to be quite modest in size. Unlike the TS in the Cope rearrangement, the TS for a 1,5-hydrogen shift in 1 is not highly variable in nature, and the reason the 1,5-hydrogen shift TS is not chameleonic is discussed.     

Synthesis and resolution of a novel chiral diamine ligand and application to asymmetric lithiation-substitution

A short, efficient synthesis of chiral 1,5-diaza-cis-decalins (7) is presented. In the lithiation of N-Boc pyrrolidine, the ligands with the smallest most electron rich R groups (Me > Et > CH2tBu > CH2CF3 approximately Bn) were most effective. In the asymmetric deprotonation/substitution of benzylic substrates, (R,R)-7 (R = Me, R' = H) conferred modest selectivity. The ready availability of both enantiomers of the 1,5-diaza-cis-decalins and the ability to tune steric and electronic properties renders these compounds an attractive new class of diamine ligands.     

Helices of boron-nitrogen hexagons and decagons. A theoretical study

Ab initio self-consistent field molecular orbital and density functional theory calculations have been performed on a series of helical boron-nitrogen structures comprised of fused hexagons and larger polygons. The presence of an even number N of rings in the boron-nitrogen [N]helicenes leads to the possibility of angular isomers. The electronic structure and stability of three isomeric nonhydrogenated boron-nitrogen helices were investigated at the HF/6-31G(d) and the B3LYP/6-31G(d) levels of theory. According to this study some of the initially assumed regular helical structures are unstable; two types of the isomeric structures convert to characteristically different equilibrium geometries. Electron density contours were calculated in order to interpret the existing bonding patterns.     

Benzyl alcohol-ammonia (1:1) cluster structure investigated by combined IR-UV double resonance spectroscopy in jet and ab initio calculation

Laser-induced fluorescence excitation and IR-UV double resonance spectroscopy have been used to determine the hydrogen-bonded structure of benzyl alcohol-ammonia (1:1) cluster in a jet-cooled molecular beam. In addition,ab initio quantum chemical calculations have been performed at HF/6-31G and HF/6-31G(d,p) levels for different ground state equilibrium structures of the cluster to correlate the calculated OH and NH frequencies and their intensities with experimental results. The broad red-shifted OH-stretching mode in the IR-UV double resonance spectrum suggests strong hydrogen bonding between the hydroxyl hydrogen and the lone pair of the ammonia nitrogen. The position and intensity distribution of the calculated NH and OH modes for the minimum-energy gauche form at HF/6-31G level have better correlation with the experimental results compared to other calculated ground state equilibrium conformers. These results lead to the conclusion that the minimum energy gauche form of the cluster is populated in the jet-cooled condition.     

1,5-Diamino-1H-1,2,3,4-tetrazolium picrate: X-ray molecular and crystal structures and ab initio MO calculations

The crystal and molecular structures of 1,5-diamino-1H-1,2,3,4-tetrazolium picrate (DATP) were determined by X-ray diffraction analysis. The tetrazolium cation in DATP has a structure with protonated N4 atom of the ring. Two amino groups in the cation are found to be rather different. The 5-amino group lies in the plane of the tetrazole ring and valence angles around the N atom are close to 120°, which indicates sp² hybridization of atomic orbital of the nitrogen atom. In contrast, valence angles around the N atom of the 1-amino group are close to tetrahedral angle, which suggests sp³ hybridization. The exocyclic C-N bond in the cation is substantially shorter than that in 1,5-diaminotetrazole. The obtained results indicate a conjugation between the π-system of the tetrazole ring and the 5-amino group. The results of ab initio calculations of electronic structure and relative stability for various tautomeric forms of protonated 1,5-diaminotetrazole using MP2/6-31G* and B3LYP/6-31G* levels of theory are in a good agreement with X-ray data and show that there are differences in σ-electron overlap populations for the C-N bonds in the cation in DATP, while π-electrons are delocalized.     

A computational investigation on the sequential rearrangement mechanism of 2-allyl-2,4,5-hexatrienaldehyde involving [1,5]-hydrogen migration and 8pi-electrocyclization

The sequential rearrangement reaction mechanism of the 2-allyl-2,4,5-hexatrienaldehyde has been studied at the unrestricted Becke three-parameter hybrid functional combined with Lee-Yang-Parr correlation functional (UB3LYP)/6-31G**, Complete Active Space Self-Consistent Field (CAS (8,8))/6-31G**, Configuration Interaction with Single and Double Excitations (CISD)//UB3LYP/6-31G** and the second-order perturbation theory based on the CASSCF reference wave function (CASPT2)//CAS(8,8)/6-31G** levels. Two pathways have been found to be involved for this reaction. The first pathway includes four processes of the rotation of the C3--C4 single bond, the stepwise [2 + 2] cycloaddition, the [1,5]-hydrogen migration, and the ring opening isomerization, while the second pathway undergoes only two processes of the [1,5]-hydrogen migration and the 8pi-electrocyclization. The calculation results indicate that the second pathway is favorable, in good agreement with the recent experimental observation. The whole reaction is stepwise and strong exothermic.     

(CH2)2N和(CH3)2NH+的密度泛函理论计算

用密度泛函理论UB3LYP／6-31G（d,p）方法研究了二甲胺自由基（CH3）2N及其质子化离子（CH3）2NH 的构象和超精细结构．在由构象研究得到的两种自由基的最稳定结构上,用密度泛函的UB3LYP和UB3PW91方法及从头计算的UHF、UMP2（FULL）方法计算了α-质子、β-质子和N核上的超精细偶合常数A（Hα）、A（Hβ）和A（N）结果表明：两种自由基中甲基内旋转的位垒均很低,分别为0．46kJ·mol-1（（CH3）2NH ）和2．6kJ·mol-1（（CH3）2N）．UB3LYP／6-31G（d,p）和UB3PW91／6-31G（d,p）计算的A（Hα）、A（Hβ）和A（N）与ESR实验结果符合得很好,UMP2／6-31G（d,p）方法的计算值与实验值符合得也较好．     

Tautomeric equilibria of pyridoxal-5'-phosphate (vitamin B6) and 3-hydroxypyridine derivatives: a theoretical study of solvation effects

The tautomeric equilibria of a series of 3-hydroxypyridine derivatives including pyridoxal-5'-phosphate (PLP), the active form of vitamin B(6), have been studied using density functional calculations (B3LYP/6-311+G//B3LYP/6-31G) in the gas phase and in different solvents. Three different approaches, namely continuum, discrete, and hybrid (combined discrete/SCRF), were employed to investigate the effects of solvation on the tautomeric equilibria. In all cases, the neutral hydroxy form is significantly more stable than the zwitterionic oxo form (by 43-56 kJ mol(-)(1)) in the gas phase. The tautomeric energies reduce substantially in the presence of a polarizable dielectric medium. However, the neutral form is calculated to be the dominant form in nonpolar and aprotic polar solvents. On the other hand, a reversal of tautomeric equilibrium, in favor of the zwitterionic form, is predicted in an aqueous medium. This study highlights the role of both water molecules and bulk solvent effect in influencing the tautomeric equilibria of the PLP related compounds. A combination of explicit microsolvation and continuum reaction field is required to account fully for the energetic effect of aqueous solvation. The tautomeric free energy differences (deltaG(298)) of PLP in the gas phase and in aprotic polar (epsilon = 40) and aqueous media are predicted to be 47, 22, and -29 kJ mol(-)(1), respectively.     

Theoretical study on the hydrogen bonding of five-membered heteroaromatics with water

The hydrogen-bonding ability of five-membered heteroaromatic molecules containing one chalcogen and two heteroatoms with nitrogen in addition to chalcogen, respectively, have been analyzed using density functional and molecular orbital methods through adduct formation with water. The stabilization energies for all the adducts are established at B3LYP/6-31+G* and MP2/6-31+G* levels after correcting for the basis set superposition error by using the counterpoise method and also corrected for zero-point vibrational energies. A natural bond orbital analysis at B3LYP/6-31+G* level and natural energy decomposition analysis at HF/6-31+G* using MP2/6-31+G* geometries have been carried out to understand the nature of hydrogen-bonding interaction in monohydrated heterocyclic adducts. Nucleus-independent chemical shift have been evaluated to understand the correlation between hydrogen bond formation and aromaticity.     

Theoretical studies on the S-N interactions in sulfoximine

The potential energy surface of sulfoximines has been searched using ab initio MO and Density Functional Calculations. The electronic structures of the isomers of sulfoximine have been studied using HF/6-31+G*, MP2(full)/6-31+G* and B3LYP/6-31+G* levels. Final energies of these molecules have been calculated at the high accuracy G2 and CBS-Q levels. Though a formal SN double bond is generally considered between sulfur and nitrogen in these systems, theoretical studies do not show any π interaction between them. S-N rotational barriers, bond dissociation energies, atomic charge analysis, and NBO analysis all indicate only a single bond across S-N with a very strong ionic interaction.     

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^*)。     

氮笼N12的量子化学研究

采用量子化学从头算方法研究了7个氮笼N₁₂,其中包括以前文献中研究过的两个氮笼N₁₂.在RHF/6-31G^*理论水平下进行全构型优化、振动频率分析和热化学计算.计算结果表明,7个结构均是势能面上的局域极小点.N₁₂(D_3d)是所有7个笼状异构体中最稳定的.能量分析表明,如果这些分子能够被合成,将会成为潜在的高能量密度材料.     

Spectroscopic analysis of 2-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-ylimino)-2-(4-nitro-phenyl) acetonitrile

The optimized geometry and vibrational frequencies of 2-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-ylimino)-2-(4-nitro-phenyl) acetonitrile (DOPNA) were obtained by ab initio DFT/B3LYP level with complete relaxation in the potential energy surface using 6-31G and 6-311G basis sets. The Fourier-transform infrared (FT-IR) spectrum of DOPNA has been recorded in the region 4000-400 cm(-1). The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR spectrum. The calculated frequencies are in comparable agreement with the experimental frequencies. The calculated energy span between the HOMO and the LUMO of DOPNA is 2.94 and 2.87eV by B3LYP/6-31G and B3LYP/6-311G, respectively.