FMO Analysis Research Articles

DFT study of the mechanism and stereoselectivity of the 1,3-dipolar cycloaddition between pyrroline-1-oxide and methyl crotonate

A theoretical study of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition reaction between methyl crotonate and pyrroline-1-oxide has been carried out using density functional theory (DFT) at the B3LYP/6-31G(d) level of theory. The reaction has been followed by performing transition state optimization, calculations of intrinsic reaction coordinate and activation energies; the molecular mechanism of the reactions is concerted and asynchronous. The regio- and exo/endo-selectivity have been explained in terms of frontier molecular orbital interactions, local and global electrophilicity and nucleophilicity indices and an analysis of the Wiberg bond indices in the transition state. The FMO analysis and DFT-based reactivity indices showed that the regioselectivity of this reaction is controlled by the HOMOdipole–LUMOdipolarophile interaction. The activation parameters indicated favoured endo approach along the meta-pathway in agreement with the experimental results. The molecular mechanism of the 1,3-dipolar cycloaddition reaction between pyrroline-1-oxide and methyl crotonate is theoretically investigated by DFT method at the B3LYP/6-31G* level. The transition states corresponding to the possible stereoisomeric pathways along regioisomeric reaction channels were searched, localized and optimized. The cycloaddition is favored along the reaction channel with the meta-endo adduct as major diastereomer in agreement with experiment.

Spectroscopic (FTIR, FT-Raman, 13C and 1H NMR) investigation, molecular electrostatic potential, polarizability and first-order hyperpolarizability, FMO and NBO analysis of 1-methyl-2-imidazolethiol

In this work, experimental and theoretical study on the molecular structure and vibrational spectra of 1-methyl-2-imidazolethiol (MIME) were presented. The vibrational frequencies of the title compound were obtained theoretically by ab initio HF and DFT (B3LYP/LSDA) employing 6-311G (d,p) and 6-311++G(d,p) basis sets and compared with experimental spectral bands (FTIR and FT-Raman). The thermodynamic properties of the studied compound have been computed at different temperatures. The atomic charges and charge delocalization of the molecule have been analyzed by natural bond orbital (NBO) analysis. The reactivity sites are identified by mapping the molecular electrostatic potential (MESP) surface. Electronic properties HOMO and LUMO energies were measured by time-dependent TD-DFT approach. Besides, 13C and 1H nuclear magnetic resonance (NMR) chemical shifts of the molecule in chloroform solvent calculated using the Gauge-Independent Atomic Orbital (GIAO) method are found to be in good agreement with experimental values.

A DFT/TDDFT modelling of bithiophene azo chromophores for optoelectronic applications

Sixteen Bithiophene azo derivatives (BTAs) containing thiazole moiety have been reported recently, and seven of them along with five new candidates have been tested for optoelectronic properties using DFT/TDDFT computations. FMO analysis clearly reveals that the substitution at bithiophene moiety largely stabilizes the HOMO while the LUMO is mainly localized on azo and thiazole moieties. Five new candidates with –NO2, –CN, –COOH, COCH3 and –COOCH3 as acceptors have been designed. Among the designed candidates, –NO2 substituted BTA (BTA8) is promising with an absorption maximum at 647 nm. Push–pull character has been quantified using NMR chemical shifts. Further, NBO analysis accounts for the n → π* and π → π* ground state stabilizing interactions arising from the heteroatoms in these BTAs. Four of the five designed candidates, are found to have reduced HOMO–LUMO energy gap, greater push–pull character along with higher wavelength of absorption and this render them very suitable for optoelectronic applications.

Synthesis and thermal reactivity of 3-benzyl-7-trifluoromethyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxide

The generation and reactivity of 1-benzyl-5-trifluoromethyl-azafulvenium methide are described. Under microwave induced pyrolysis this intermediate could be trapped by dipolarophiles acting as a 4π as well as 8π dipole. It was observed that with dimethyl acetylenedicarboxylate the 1,3-dipolar cycloadduct was the major product whereas with N-substituted maleimides the major product results from the addition across the 1,7-position. FMO analysis of the cycloadditions corroborated the rationalization of the observed reactivity. Quantum chemical calculations carried out at the DFT level of theory allowed the rationalization of the stereoselectivity observed in the cycloaddition of 1-benzyl-5-trifluoromethyl-azafulvenium methide with N-substituted maleimides. The study revealed that exo-cycloaddition is the main reaction path for the 1,7-cycloaddition, while the endo-approach is the main mode of reaction leading to 1,3-cycloadducts. In addition, under flash vacuum pyrolysis or conventional thermolysis, 1-benzyl-5-trifluoromethyl-azafulvenium methide undergoes an allowed suprafacial sigmatropic [1,8]H shift leading to the efficient formation of 2-methyl-1-styryl-3-trifluoromethyl-1H-pyrrole.

A theoretical investigation of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition of C-diethoxyphosphoryl-N-methylnitrone with substituted alkenes

Abstract A theoretical study of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition of C -diethoxyphosphoryl- N -methylnitrone with substituted alkenes (allyl alcohol and methyl acrylate) is carried out using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis and DFT-based reactivity indices confirmed the experimental ortho regioisomeric pathway. Potential energy surface analysis shows that these 1,3-dipolar cycloaddition reactions favor the formation of the ortho-trans cycloadduct in both cases. The obtained results are in agreement with experimental data.

Cycloaddition of trifluoromethyl azafulvenium methides: synthesis of new trifluoromethylpyrrole-annulated derivatives

The chemistry of trifluoromethyl azafulvenium methides was explored leading to a new route to trifluoromethylpyrrole-annulated systems. The first evidence of azafulvenium methides acting as 1,3-dipoles is reported. These azafulvenium methides showed site selectivity in the reaction with strong electron-deficient dipolarophiles leading exclusively to 1,3-cycloadducts. In the cycloaddition with less-activated dipolarophiles 1,7-cycloadducts resulting from [8π+2π] cycloaddition are also formed. FMO analysis of the cycloaddition reactions allowed the rationalization of the observed selectivity.

Mechanism, Regioselectivity, and the Kinetics of Phosphine‐Catalyzed [3+2] Cycloaddition Reactions of Allenoates and Electron‐Deficient Alkenes

With the aid of computations and experiments, the detailed mechanism of the phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes has been investigated. It was found that this reaction includes four consecutive processes: 1) In situ generation of a 1,3-dipole from allenoate and phosphine, 2) stepwise [3+2] cycloaddition, 3) a water-catalyzed [1,2]-hydrogen shift, and 4) elimination of the phosphine catalyst. In situ generation of the 1,3-dipole is key to all nucleophilic phosphine-catalyzed reactions. Through a kinetic study we have shown that the generation of the 1,3-dipole is the rate-determining step of the phosphine-catalyzed [3+2] cycloaddition reaction of allenoates and electron-deficient alkenes. DFT calculations and FMO analysis revealed that an electron-withdrawing group is required in the allene to ensure the generation of the 1,3-dipole kinetically and thermodynamically. Atoms-in-molecules (AIM) theory was used to analyze the stability of the 1,3-dipole. The regioselectivity of the [3+2] cycloaddition can be rationalized very well by FMO and AIM theories. Isotopic labeling experiments combined with DFT calculations showed that the commonly accepted intramolecular [1,2]-proton shift should be corrected to a water-catalyzed [1,2]-proton shift. Additional isotopic labeling experiments of the hetero-[3+2] cycloaddition of allenoates and electron-deficient imines further support this finding. This investigation has also been extended to the study of the phosphine-catalyzed [3+2] cycloaddition reaction of alkynoates as the three-carbon synthon, which showed that the generation of the 1,3-dipole in this reaction also occurs by a water-catalyzed process.

Kinetic and Thermodynamic Aspects of the CT and T‐Shaped Adduct Formation Between 1,3‐Dimethylimidazoline‐2‐thione (or ‐2‐selone) and Halogens

AbstractThe reactions between L=E donors [L: 1,3‐dimethylimidazolyl framework; E: S (1), Se (2)] and halogens X2 (X: Cl, Br, I) to form either “T‐shaped” hypervalent chalcogen (TY) or linear charge‐transfer‐type adducts (CT) have been studied in the density functional theory (DFT) context by considering both thermodynamic and kinetic aspects. Apart from the case of the adducts between sulfur donors and diiodine, hypervalent compounds are calculated to be always more stable than CT ones in the gas phase, in agreement with the experimental results based on spectroscopic and structural determinations. NBO and FMO analyses suggest explanations for this. Reaction mechanism studies reveal that CT adducts are always the first products of the reactions and no transition states connecting the reactants directly to TY adducts have been found. The present calculations indicate that, at least for 1 and 2, TY adducts are obtained from CT adducts and not directly from the reactants.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Photocyclodimers from Z-ligustilide. Experimental results and FMO analysis

The irradiation of the natural phthalide Z-ligustilide ( 1 ) gave the natural dimeric phthalide riligustilide ( 5 ), and three novel dimeric phthalides 7 , 8 and 9 . The chemo- and regio-selectivity involved in the formation of the photocyclodimers were analyzed by use of frontier molecular orbital methods and the preference in the formation of 7 was supported by the theoretical analysis.

Reactivity of heterophospholes toward 1,3‐dipolar cycloaddition of diazo compounds—an FMO analysis

AbstractThe molecular geometries and the frontier orbital energies of three diazo compounds [diazodiphenylmethane (2), the α‐silyl‐α‐diazoketone 3 and the isomeric 2‐siloxy‐1‐diazoalkene 4], 10 heterophospholes with a PC bond and two heterophospholes with a PN bond were obtained from DFT calculations at the B3LYP/6–311+G** level. The 1,3‐dipolar cycloaddition reactivity of diazo compounds 2–4 toward the heterophospholes is discussed on the basis of FMO theory. It is concluded that in most cases, the dominant frontier orbital interaction is between the HOMO(diazo) and the LUMO(heterophosphole), and that the reactivity should decrease in the order­2 >4 >3. The 1,2‐thiaphosphole 9 and 1,3‐azaphosphole 10 have HOMOs of high energy and, therefore, the HOMO(heterophosphole)–LUMO(diazo) interaction is also important. Among the different types of heterophos‐pholes considered here, the 2‐acyl‐1,2,3‐diazaphosphole 5, 3H‐1,2,3,4‐triazaphosphole 8, 1,2‐thiaphosphole 9 and 1,3,4‐thiazaphosphole 14 are predicted to have the highest dipolarophilic reactivities. These conclusions are in qualitative agreement with available experimental results. Copyright © 2003 John Wiley & Sons, Ltd.

An experimental and theoretical study on the substituent effect of the permanganate oxidation of styrenes.

The kinetic data obtained for the cycloadditions of the permanganate ion to a series of styrene derivatives in dichloromethane solution in the presence of a quaternary ammonium ion were examined with two theoretical approaches, on the assumption that the reactions proceed via a concerted [3 + 2] mechanism. The semi-quantitative frontier molecular orbital analysis of the kinetic data shows a linear free energy relationship with better correlation than the Hammett plot with a values when the point for p-NO2 group is omitted. Further examination of the results of the FMO analysis reveals that the deviation of the point for p-nitrostyrene is attributed to the transition structure being more reactant-like than that of the other derivatives. The plot of log k2 vs. -deltaG++ calculated by the density functional theory (Becke3LYP) follows a straight line with the desired correlation for all the substituents. A marked tendency was observed for the MO calculations to underestimate the deltaG++ value for electron-withdrawing substituents when the calculation was carried out excluding the quaternary ammonium ion. This inconsistency was much improved by the calculations incorporating the quaternary ammonium ion. The actual values of deltaG++ obtained from the Eyring analysis are in good agreement with those calculated at the B3LYP/6-311 +G(d,p)//B3LYP/ LanL2DZ level.

Tandem cyclization-cycloaddition behavior of rhodium carbenoids with carbonyl compounds: stereoselective studies on the construction of novel epoxy-bridged tetrahydropyranone frameworks.

Investigations and stereoselective studies on the tandem reactions of carbonyl ylides generated from alpha-diazo ketones in the presence of carbonyl compounds are presented in this paper. Intramolecular cyclization of rhodium carbenoids generated the transient five- or six-membered-ring carbonyl ylide dipoles, which efficiently underwent 1,3-dipolar cycloaddition reactions with various dipolarophiles such as aromatic aldehydes 15, alpha,beta-unsaturated aldehydes 18/24, alpha,beta-unsaturated ketones 27/28/31, and dienone 34. The transient carbonyl ylides underwent cycloadditions with various aromatic aldehydes to furnish diverse epoxy-bridged tetrahydropyranone ring systems in a diastereoselective manner. The cycloaddition of carbonyl ylides with alpha,beta-unsaturated aldehydes 18/24 or dienone 34 afforded C=O addition products in a chemoselective manner despite the presence of C=C bonds in the above dipolarophiles. Alternatively, the cycloaddition of carbonyl ylides with alpha,beta-unsaturated ketones 27/28 provided both the C=O and C=C cycloaddition products. The cycloaddition of carbonyl ylides with carbonyl compounds occurred in good yields and was found to be highly regio- and stereoselective. Single-crystal X-ray analyses were performed to unambiguously establish the structure and stereochemistry of the novel epoxy-bridged tetrahydropyranone ring systems 35a/38. Compound 35a exhibited both intermolecular C-H...O and intramolecular C-H...pi interaction motifs in the solid-state architecture. The regio-, chemo-, and stereoselectivity observed in these reactions have been investigated by semiempirical AM1 MO calculations. FMO analyses and transition state calculations have been performed for the cycloaddition of carbonyl ylides with alpha,beta-unsaturated carbonyl compounds such as tetracyclone (34) and cyclopentenone (27a). Both FMO and transition state calculations correctly predicted the regio- and stereochemistry of the cycloadducts. The calculations further revealed that a severe steric interaction caused by the phenyl rings present in dipolarophile 34 with dipole 14a increases the activation barrier of the transition state during the cycloaddition process.

Theoretical study of the bonding capabilities of 1,4-diaza-1,3-butadiene and cis-1,3-butadiene ligands in cyclopentadienyl tantalum(V) complexes

A folded envelope geometry is generally encountered in structurally characterized high valent early transition metal compounds containing a substituted 1,4-diaza-1,3-butadiene ligand. In these cases the diazabutadiene ligand can be regarded as dianionic ene-diamido ligand and the folded five-membered ring can be described as a metallacyclo-2,5-diazapent-3-ene. A comparable metallacyclopent-3-ene description is attributed to η 4-butadiene complexes of early transition metals, in which the ligand exhibits a σ 2, π-character. For this reason, a parallel description was initially adopted by several authors for the ene-diamido ligands and the origin of the folding of the five-membered ring was attributed to the saturation of the metal center through the CC double bond. The aim of this paper is to discriminate the bonding capabilities of the 1,4-diaza-1,3-butadiene and cis-1,3-butadiene ligands on high-valent tantalum complexes, and to establish the origin of the folding of the 1,4-diaza-1,3-butadiene ligand. A Density Functional study (DFT) of the model complex [CpTaCl 2(HNCHCHNH)] ( 1) and compound [CpTaCl 2(η 4-butadiene)] ( 2) has been carried out. The differences in the bonding description of these ligands coordinated to the identical [CpTaCl 2] moiety are discussed through the examination of the HOMOs of 1 and 2 and on the basis of a FMO analysis. In complex 1, there is no evidence of any positive overlap between the tantalum center and the inner carbon atoms of the diazabutadiene ligand, while for 2 the classical σ 2,π-description for the η 4-butadiene ligand is well-founded. Consequently, the generally accepted bonding description of 1,4-diaza-1,3-butadiene ligands coordinated to high valent early transition complexes should be modified. The origin of the folding is the reorientation of the N hybrid orbitals with the purpose of saturating the metal center and no significant donation through the CC bond occurs.

Etude DFT du mécanisme des réactions de cycloaddition dipolaire-1,3 de la C,N-diphénylnitrone avec des dipolarophiles fluorés de type éthylénique et acétylénique

Structures and energetics of reactants, transition states and cycloadducts of cycloadditions of nitrone with three-fluorinated dipolarophiles have been investigated with the density functional theory method B3LYP/6-31G*. Analysis of the results on the different reaction pathways shows that the reaction takes place along a concerted mechanism and proceeds more or less synchronously. The FMO analysis shows a strong HOMOdipole–LUMOdipolarophile interaction as the principal reason for the reactivity in these 1,3-dipolar cycloaddition reactions. Regioselectivity of the products of the reaction is predicted reliably by our calculations, the results provide a good prediction of the relatives rates observed experimentally as the dipolarophiles are varied.

Diels-Alder reaction of 4-bromo-6-spiroepoxycyclohexa-2,4-dienone with electron-rich and neutral dienophiles

Spirodienone 1, prepared by Adler-Becker oxidation of 4-bromo-2-hydroxymethylphenol, undergoes [4+2] cycloaddition with various dienophiles (enol ethers, enol esters, styrenes, N-methylvinylacetamide) under thermal conditions (20–160°C). Three sets of experiments have been carried out, either with CH 2Cl 2 as solvent or neat with 1, or under tandem oxidation-cycloaddition conditions with phase-transfer catalysis. Complete regio- and syn diastereofacial selectivities were obtained but a switch in endo/exo selectivity has been observed between enol ethers and styrenes ( endo addition), enol esters (low selectivity) and an enamide ( exo addition). The FMO analysis confirms that theses reactions are under LUMO disne control and that the observed regioselectivity is in agreement with orbital coefficients. Except for vinyl acetate, the formation of the major isomer is qualitatively confirmed at the AM1 level.

Theoretical study of the C- vs. O-Acylation of metal enolates. Frontier molecular orbital analysis including solvent effects

An extended version of the Klopman–Salem equation of chemical reactivity, which incorporates the effect of an external electrostatic field in both charge and orbital contributions, has been applied to analyze the reactivity pattern of ambident metal enolates towards acylation reactions in different solvents. The results are consistent with the experimental observation that the proportion of C-acylation product is enhanced for solvents of low polarity where a relevant orbital control contribution is predicted. Comparison between the cis/trans proportion of C- and O-acylation products are also qualitatively accounted for by the FMO analysis. © 1993 John Wiley & Sons, Inc.

A new insight from qualitative MO theory into the problem of the FeFe bond in Fe 2(CO) 9

A revision of EHMO calculations with FMO analysis has provided new qualitative insight into the bonding network in Fe 2(CO) 9 and reconciled the previous diverging interpretations. After separation of all of the Fe(CO) bridge bonding/antibonding levels (12 electrons for six FeC bonds) there remains a two-electron/two-orbital interaction (σ/σ ★) that is ultimately responsible for a direct (through-space) FeFe bond. However, predominant repulsive interactions via the CO bridges (through-bond) may hide the linkage.

The IRC method in chemical reactions: Reaction ergodography for the addition of LiH to acetylene

The ab initio calculation have been performed on the addition of LiH to acetylene at RHF/3-21G basis set. The geometries and energies of the isolated reactant, molecular complex, transition state and product have been determined on the singlet potential energy surface of the ground state. Our results indicate that there is a meta stable molecular complex near the isolated reactant in the reaction pathway. The process from isolated reactant to molecular complex is a non-bonding-exchanging reaction process, and the process from molecular complex to product is the rate-controlling step of the reaction. We also estimate the activated entropy and the frequency factor of the rate-controlling step by using the RRKM theory. The FMO analysis for the transition state reveals the HOMO of transition state to be formed from both HOMO-LUMO and HOMO-HOMO interactions.

Regioselectivity in the diels-alder reactions of α-pyrones with alkynes

4-Ethyl-5-methyl-6-methylthio-2(H)-pyranone (4) undergoes Diels-Alder reactions with ethyl hexynoate (5), 3-heptyn-2-one (6), ethyl propiolate (7), and 3-butyn-2-one (8) to afford substituted benzenes with high regioselectivity upon extrusion of CO 2. 4-Ethyl-5,6-dimethyl-(1), 4-ethyl-3,6-dimethyl-(2) and 4-ethyl-5-methyl-(2H)-pyranone (3) gave excellant to good regioselectivity with internal alkynes 5 and 6 and poor regioselectivity with terminal alkynes 7 and 8. MNDO calculations have been carried out on the pyrones and alkynes and qualitative FMO analysis correctly predicts the major products.

A novel regiospecific intramolecular cycloaddition of an aromatic ring. Molecular orbital study of conjugated ketenes thermally generated from six-membered α-monocarbonyl azo-compounds

When a methylene dichloride solution containing 4,4-diarylphthalazin-1(4H)-one(3) was warmed above –50 °C, nitrogen extrusion occurred to result in the formation of the quinonoid ketene (19). The quinonoid ketene thus generated underwent a facile and regiospecific intramolecular [π4a+π2a] cycloaddition with NN-dimethylaniline to afford a norcaradiene (22), followed by ring opening to an azulenone derivative (14). It was found, however, that this process takes place only with an aromatic ring bearing strong electron-donating substituents such as dialkylamino groups. FMO analyses based on the model system calculated by the CNDO/2 method showed that the dominant HOMO–LUMO interaction in the transition state should involve the HOMO of NN-dialkylaniline and LUMO of the quinonoid ketene. Thus, the in-plane π*-orbital induces the orthogonal approach of the two components favouring an antarafacial pathway and the cyclisation is initiated by preferential bond formation between the central carbon of the ketene moiety and the para-carbon of NN-dialkylaniline to result in the formation of (22).