Conformational preferences of methacrolein in Diels-Alder and 1,3-dipolar cycloaddition reactions

A B3LYP/6-31G* study has been carried out for the reactions of methacrolein with cyclopentadiene, parent nitrone, 1-pyrroline-1-oxide, and (Z)-C,N-diphenylnitrone, in which the coordination of a Lewis acid (borane) and the solvent polarity (dichloromethane) have been taken into account. Calculated activation parameters, regioselectivities (for 1,3-dipolar cycloaddition reactions), and endo/exo stereoselectivities show good agreement with available experimental data. Gas-phase calculations show a varied behavior of the s-cis/s-trans TS stability for noncatalyzed reactions (from the systematic s-cis preference for the cyclopentadiene reaction to the systematic s-trans predilection encountered in the diphenylnitrone cycloaddition). BH3 coordination leads to a preferential stabilization of s-trans TSs in the reactions of cyclopentadiene (exo approach) and diphenylnitrone but a larger stabilization of s-cis structures in the processes involving the parent nitrone or 1-pyrroline-1-oxide. Additionally, a rather systematic preferential stabilization of s-trans structures is induced by solvent polarity in most reactions. As a consequence, an s-trans preference is predicted in solution for both thermal and catalyzed types of reactions in most approaches. Such a conclusion is consistent with some experimental results suggesting a preference for a particular conformation of the methacrolein-Lewis acid complexes.     

Origins of stereoselectivity in the Diels-Alder addition of chiral hydroxyalkyl vinyl ketones to cyclopentadiene: a quantitative computational study

Modest basis set level MP2/6-31G(d,p) calculations on the Diels-Alder addition of S-1-alkyl-1-hydroxy-but-3-en-2-ones (1-hydroxy-1-alkyl methyl vinyl ketones) to cyclopentadiene correctly reproduce the trends in known experimental endo/exo and diastereoface selectivity. B3LYP theoretical results at the same or significantly higher basis set level, on the other hand, do not satisfactorily model observed endo/exo selectivities and are thus unsuitable for quantitative studies. The same is valid also with regard to subtle effects originating from, for example, conformational distributions of reactants. The latter shortcomings are not alleviated by the fact that observed diastereoface selectivities are well-reproduced by DFT calculations. Quantitative computational studies of large cycloaddition systems would require higher basis sets and better account for electron correlation than MP2, such as, for example, CCSD. Presently, however, with 30 or more non-hydrogen atoms, these computations are hardly feasible. We present quantitatively correct stereochemical predictions using a hybrid layered ONIOM computational approach, including the chiral carbon atom and the intramolecular hydrogen bond into a higher level, MP2/6-311G(d,p) or CCSD/6-311G(d,p), layer. Significant computational economy is achieved by taking account of surrounding bulky (alkyl) residues at 6-31G(d) in a low HF theoretical level layer. We conclude that theoretical calculations based on explicit correlated MO treatment of the reaction site are sufficiently reliable for the prediction of both endo/exo and diastereoface selectivity of Diels-Alder addition reactions. This is in line with the understanding of endo/exo selectivity originating from dynamic electron correlation effects of interacting pi fragments and diastereofacial selectivity originating from steric interactions of fragments outside of the Diels-Alder reaction site.     

Origin of the “endo rule” in Diels–Alder reactions

Detailed density functional theory calculations definitively rationalize the preference for the endo cycloadduct (also known as endo rule) in text‐book thermal Diels–Alder reactions involving maleic anhydride and cyclopentadiene or butadiene. This selectivity is mainly caused by an unfavorable steric arrangement in the transition‐state region of the exo pathway which translates into a more destabilizing activation strain. In contrast with the widely accepted, orbital‐interaction‐based explanation for the endo rule, it is found that neither the orbital interactions nor the total interaction between the deformed reactants contributes to the endo selectivity. © 2013 Wiley Periodicals, Inc.     

Thermal rearrangements of 2-vinylcyclopropylidene to cyclopentadiene and vinylallene: a theoretical investigation

In an attempt to clarify the favored rearrangement reaction of vinylcyclopropylidenes, the prototype thermal rearrangements of singlet 2-vinylcyclopropylidene (1) leading to 1,3cyclopentadiene (2) and 1,2,4-pentatriene (vinylallene) (3) were investigated by means of ab initio quantum-mechanical electronic-structure calculations. The B3LYP functional with the 6-31G(d) basis set was employed for geometry optimization of the equilibrium and transition-state structures relevant to the two reaction pathways and for computing their harmonic vibrational frequencies. Final energies were evaluated by single-point calculations at the CCSD(T) level of theory with the 6-311 + G(3df,2p) basis set. The rearrangement of s-cis 1 to 2 is found to occur by a three-step pathway. The first step involves the formation of a nonclassical carbene (5), which is an internal pi complex between the pi molecular orbital of the double bond and the empty p atomic orbital of the carbene carbon. In the second step, the nonplanar five-membered ring geometry of 5 flattens to reach the planar structure of 3-cyclopentenylidene (4). The last step is the 1,2-migration of a alpha-hydrogen atom to the carbene center in 4. The rate-determining step for the rearrangement of s-cis 1 to 2 is the formation of 5, with a predicted global deltaG++(220 K) of only 0.6 kcalmol(-1). The rearrangement of s-trans 1 to 2 requires an initial conversion of s-trans 1 to the s-cis conformer, with a predicted deltaG++(220 K) of 1.8 kcalmol(-1). The transition structure for the ring-opening of s-trans 1 into s-trans 3 (deltaG++(220 K)=4.7 kcalmol(-1)) is more energetic than that for the ring-opening of s-cis 1 into s-cis 3 (deltaG++(220 K)=2.5 kcalmol(-2)) due to larger repulsive nonbonded H...H interactions in the former transition structure. On the basis of these results, it is suggested that if the reaction of 1,1-dibromo-2-vinylcyclopropane with methyllithium at -78 degrees C leads to the initial formation of carbene 1, then the reaction should yield 2 as the main product together with small amounts of 3. This theoretical prediction nicely agrees with experimental findings.     

The first density functional study on the

The hetero-Diels-Alder reactions of 1,2-diaza-1,3-butadiene with ethylene, methyl vinyl ether, and methyl acrylate have been investigated theoretically with the aid of density functional theory using the Becke3LYP/6-31G(d) computational level. In the reactions with substituted alkenes, the transition states are concerted but asynchronous; the shortest bond-forming distance involves the nonsubstituted carbon of the alkene. In agreement with the experimental results, the reaction with methyl vinyl ether proceeds with high endo stereoselectivity and with complete regioselectivity to form the 6-methoxy cycloadduct. The conformational study of the transition states shows a sharp s-trans preference. In contrast, the [4 + 2]-cycloaddition of 1,2-diaza-1,3-butadiene with methyl acrylate have been found to occur with low regio- and stereoselectivity but with a s-cis preference in the transition structures.     

The origin of endo stereoselectivity in the hetero-Diels-Alder reactions of aldehydes with ortho-xylylenes: CH-pi,pi-pi,and steric effects on stereoselectivity

Theoretical studies of stereoselectivity have been carried out with B3LYP and MP2 calculations. The high endo selectivity of hetero-Diels-Alder reactions of ortho-xylylenes with acetaldehydes is shown to result from attractive CH-pi interactions between alkyl groups of the aldehyde and the aromatic ring in the transition states of the reaction. For the hetero-Diels-Alder reactions of ortho-xylylenes with benzaldehyde, the stereoselectivity is shown to be mainly governed by the attractive pi-pi interactions between the phenyl rings of the benzaldehyde and the ortho-xylylene. MP2 calculations are necessary to reproduce the stabilizing dispersion interactions.     

Ab Initio Study of Endo/Exo and Diastereofacial Selectivities in Diels-Alder Reactions between Chiral Butenolides and Cyclopentadiene

Diels-Alder reactions of cyclopentadiene with crotonolactone and beta-angelica lactone have been studied using ab initio methods at the MP3/6-31G//RHF/3-21G and MP2/6-31G//RHF/6-31G levels. The transition states corresponding to the formation of different stereoisomers and diastereoisomers have been located. The results obtained show that the correct endo/exo selectivity is only obtained when polarization functions are included in the basis set. However, syn/antiselectivity is correctly described at all levels of calculation.     

Structural assignment of Diels-Alder adducts: an experimental and theoretical approach

A detailed NMR analysis with total assignment of (1)H and (13)C NMR data for the endo and the exo adducts, obtained by Diels-Alder reaction between 2-cyclohexenone and cyclopentadiene, is described. The unequivocal assignment of the endo and exo structures was performed by (1)H and (13)C NMR. These assignments were supported by theoretical chemical shift calculations at GIAO/HF level using 6-311 + g(2d, p) from optimized structures at the B3LYP/6-31g(d) level.     

Solvent effects on endo/exo selective in (4 + 2) cycloadditions of cyanoethylenes.

SCRF calculations on transition structures of cycloadditions of acrylonitrile and maleonitrile to cyclopentadiene and 1,3-butadiene show that the experimentally observed endo preference for the cycloaddition of acrylonitrile to cyclopentadiene is the consequence of solvent influence and not the result of secondary orbital interactions.     

Diastereoselective Diels-Alder reactions of alpha-fluorinated alpha,beta-unsaturated carbonyl compounds: chemical consequences of fluorine substitution. 2

Two alpha-fluoro alpha,beta-unsaturated carbonyl compounds, i.e., benzyl 2-fluoroacrylate (3) and 2-fluorooct-1-en-3-one (4), as well as the corresponding nonfluorinated parent compounds, were synthesized and subjected to Diels-Alder reactions with cyclopentadiene. The cycloadditions were conducted thermally, microwave-assisted, and Lewis acid-mediated (TiCl(4)). The fluorinated dienophiles exhibited a lower reactivity and exo diastereoselectivity, while the corresponding nonfluorinated parent compounds reacted endo selectively. DFT calculations suggest that kinetic effects of fluorine determine the stereoselectivity rather than higher thermodynamic stability of the exo products.     

Direct identification of conformational isomers of adsorbed oligothiophene on Cu100

A direct conformational analysis using scanning tunneling microscopy (STM) has been performed for individual adsorbed alpha-octithiophene molecules on Cu(100). s-cis and s-trans conformational isomers are induced by the rotational flexibility of individual thiophene rings. By adding bulky N-silyl substituents to octithiophene, we successfully identify the s-cis and s-trans conformational isomers using STM. The obtained relative abundances of the s-cis and s-trans conformations are analyzed using ab initio molecular orbital calculations.     

Formal intermolecular 4 + 4 approach to cyclooctanoids: 4 + 3 capture of the Nazarov oxyallyl intermediate with simple 1,3-dienes

[reaction: see text] Simple 1,4-dien-3-ones and 1,3-dienes react in the presence of BF(3).OEt(2) via a domino Nazarov electrocyclization/intermolecular [4 + 3]-cycloaddition sequence to furnish keto-bridged cyclooctenes in good yield. Most cases showed high diastereofacial selectivity and/or endo/exo selectivity, and surprising levels of regioselectivity were observed when isoprene was used as the diene partner.     

Diastereoface-discriminative metal coordination in asymmetric synthesis: D-pantolactone as practical chiral auxiliary for Lewis acid catalyzed Diels-Alder reactions

TiCl₄-catalyzed Diels-Alder additions of the acrylate of commercial D-pantolactone to cyclopentadiene, isoprene and butadiene proceed with very high diastereofacial selectivity. Practical and mechanistic aspects of these reactions are discussed.     

Diels-Alder Addition of Dicyclopentadiene with Cyclopentadiene in Polar Solvents

Diels-Alder addition of dicyclopentadiene and cyclopentadiene in polar solvents has been studied to produce tricyclopentadiene（TCPD） that is a potential high-density fuel precursor. GC and MS analysis shows that the adducts contain two isomers, namely exo- and endo-TCPD. Theoretical simulation shows that although the transition state of endo-TCPD has a lower activation energy, exo-TCPD is thermodynamically preferred. Polar solvents can accelerate the reaction rate and improve the exo/endo ratio of TCPD because the transition state of exo-TCPD has a higher polarity than that of endo-TCPD. The solvent effect follows the order of polarity： benzyl methanol〉cyclohexanone〉toluene. The conversion rises when the temperature ranges from 120 to 150 ℃, but the selectivity of TCPD slightly decreases. Increasing the pressure can improve the conversion but the exo/endo ratio of TCPD is unchanged. The apparent kinetics in different solvents was determined via nonlinear regression. The activation energies are 99.47, 101.15, and 107.32 kJ/mol for benzyl methanol, cyclohexanone, and toluene, respectively. The optimal reaction conditions are as follows： benzyl methanol as solvent, temperature 150 ℃, and pressure 900 kPa. After an 11-hour reaction, a conversion of 58.0%, a TCPD selectivity of 95.7%, and an exo/endo ratio of 1/5.3 has been obtained.     

Peroxy acid epoxidation of acyclic allylic alcohols. Competition between s-trans and s-cis peroxy acid conformers

[Reaction: see text]. RB3LYP calculations, reported here, indicate that peroxy acid s-cis conformer is more stable than its s-trans counterpart, in agreement with experimental data. Difference in stability is the highest in the gas phase, but it falls considerably on going from the gas phase to moderately polar solvent. In the case of peroxy formic acid, the enthalpy (free energy) difference is about 3.4 (2.5) kcal/mol, respectively, in the gas phase but decreases to 1.2 (0.6) kcal/mol in dichloromethane solution. Introduction of an alkyl or aryl substituent on the peroxy acid, that is, on passing to peroxy acetic, peroxy benzoic (PBA), and m-chloroperoxy benzoic acid (MCPBA), adds a further significant (1.0-1.5 kcal/mol) favor to the s-cis isomer. RB3LYP/6-31+G(2d,p) calculations on the epoxidation of 2-propenol with peroxy formic and peroxy benzoic acids, respectively, suggest that the less stable peroxy acid s-trans conformer can compete with the more stable s-cis form in epoxidation reaction of these substrates. Transition structures arising from s-trans peroxy acids ("trans" TSs) retain both the well-established, for "cis" TS, perpendicular orientation of the O-H peroxy acid bond relative to the C=C bond and the one-step oxirane ring formation. These TSs collapse to the final epoxide via a 1,2-H shift at variance with the 1,4-H transfer of the classical Bartlett's "cis" mechanism. The "trans" reaction pathways have a higher barrier in the gas phase than the "cis" reaction channels, but in moderately polar solvents they become competitive. In fact, the "trans" TSs are always significantly more stabilized than their "cis" counterparts by solvation effects. Calculations also suggest that going from peroxy formic to peroxy benzoic acid should slightly disfavor the "trans" route relative to the "cis" one, reflecting, in an attenuated way, the decrease in the peroxy acid s-trans/s-cis conformer ratio. The predicted behavior for MCPBA parallels that of PBA acid.     

On the endo/exo stereoselectivity of intramolecular Diels-Alder reactions of hexadienylacrylates: an interesting failure of density functional theory

[formula: see text] A combined experimental and computational study of endo/exo stereoselectivity in a series of IMDA reactions of hexadienylacrylates has found that DFT makes erroneous predictions when the endo and exo transition states possess differing degrees of conjugation. These problems are overcome by carrying out calculations at the MP2 level of theory, which gives remarkably accurate Boltzmann distributions of products. These findings are used to predict ways to obtain either endo- or exo-cycloadducts exclusively.     

Counterions of BINAP-Pt(II) and -Pd(II) complexes: novel catalysts for highly enantioselective Diels-Alder reaction

[formula: see text] Platinum and palladium chiral bisphosphine complexes and their counterion effects in asymmetric Diels-Alder reactions have been investigated. The reaction of cyclopentadiene and various bidentate dienophiles in the presence of a catalytic amount of Pt(II)- or Pd(II)-BINAP complex proceeds with excellent endo/exo selectivity as well as endo enantioselectivity (up to 99% ee).     

Conformational thermodynamic and kinetic parameters of methyl-substituted 1,3-butadienes

The s-trans/s-cis conformational equilibria of 10 methyl-substituted 1,3-butadienes [(E)- and (Z)-1,3-pentadiene; 2-methyl-1,3-butadiene; (E)-2-methyl-1,3-pentadiene; 2,3-dimethyl-1,3-butadiene; (E,E)-, (E,Z)-, and (Z,Z)-2,4-hexadiene; 2,5-dimethyl-2,4-hexadiene; and (E,E)-2,4-dimethyl-2,4-hexadiene] were explored by trapping high-temperature conformational equilibria by cryogenic deposition. The vapor state enthalpy differences of these s-trans/s-cis conformers, DeltaH(t equilibrium c), were determined by varying the equilibrating temperature and integrating the resulting matrix isolated IR spectra. The results obtained are in good agreement with ab initio calculations at the G3 level. From these thermodynamic parameters, methyl group nonbonded interactions in conjugated 1,3-butadienes were delineated. Rates of decay of s-cis conformers to their s-trans rotamers were obtained in the solid-state by warming up trapped high-temperature equilibrated samples formed from neat depositions. These data were analyzed in terms of dispersive kinetics with matrix site effects in the solid-state modeled by a Gaussian distribution of activation energies. The activation barriers thus obtained were compared with G3 calculations of the enthalpies of activation.     

Conformational stability, optimized geometries, vibrational and electronic spectra of methacryloyl bromide in ground and excited electronic states

In order to understand conformational isomerism in methacryloyl bromide (MABR) in the ground (S(0)) and the first excited (S(1)) electronic states and to interpret the vibrational and electronic spectra of its conformers in the S(0) state, quantum mechanical calculations using Density Functional Theory (DFT) and RHF methods with extended basis sets 6-31G, 6-31G** and 6-311+G(d,p) have been conducted. In RHF calculations, electron correlation effects have been included at the M?ller-Plesset MP2 level. It is inferred that in both the electronic states the molecule may exist in two isomeric forms-s-trans and s-cis; the former being more stable than the later by about 1.629 kcal mol(-1) in the S(0) state and by about 2.218 kcal mol(-1) in the S(1) state. Electronic transition tends to increase the s-trans/s-cis and s-cis/s-trans, rotational barriers from 7.059 kcal mol(-1) (2468.1 cm(-1)) and 5.428 kcal mol(-1) (1897.8 cm(-1)) in S(0) state to 23.594 kcal mol(-1) (8249.4 cm(-1)) and 21.376 kcal mol(-1) (7473.9 cm(-1)) in the S(1) state. Completely optimized geometries of the two conformers in S(0) state reveal that while there is no significant difference in their bond lengths, some of the bond angles associated with COBr group are appreciably different. Electronic excitation tends to change both the bond lengths and bond angles. Based on suitably scaled DFT and RHF results obtained from the use of 6-31G** and 6-311+G(d,p) basis sets, a complete assignment is provided to the fundamental vibrational bands of both the s-trans and s-cis conformers in terms of frequency, form and intensity of vibrations and potential distribution across the symmetry coordinates in the S(0) state and a comparison has been made with experimental assignments. A theoretical prediction of the electronic transitions in the near UV-region in the two conformers and their tentative assignment has been provided on the basis of CI level calculations using 6-31G basis set.     

Stereoselectivity in Diels-Alder reactions of diene-substituted N-alkoxycarbonyl-1,2-dihydropyridines

Diene substituent effects on the regiochemical and stereochemical outcomes of uncatalyzed Diels-Alder reactions of N-alkoxycarbonyl-1,2-dihydropyridines with both styrene and methyl vinyl ketone (MVK) were studied. Alkyl substitution on the diene in all cases examined resulted in a kinetic preference for 7-endo isomers (7-phenyl 51-96% exo and 7-acetyl 54-96% exo). For both dienophiles, the highest stereoselectivities (>or=89% endo) were observed with 5-methyl or 6-methyl substituents in the dihydropyridine. Theoretical calculations of the energies of gas phase endo and exo transition states at the RHF/3-21G(*) predict that total entropy, DeltaStotal, considerations favor endo cycloadducts for both dienophiles with DHP, while total energy considerations, DeltaEo, favor endo cycloadducts for styrene and exo cycloadducts for MVK. At this level, favored endo-phenyl isomers are correctly predicted for styrene reactions, but the calculation of 7-acetyl exo or endo isomer dominance is diene-substituent-dependent for MVK reactions. The preference for endo addition of MVK to the parent, 5-methyl, and 6-methyl-DHPs was successfully predicted by calculations at the B3LYP/6-31G* theory level.