Indium trichloride: a useful catalyst for ionic Diels–Alder reactions

Indium trichloride (20 mol%) in nitromethane permits ionic Diels–Alder reaction of a variety of 2,3-olefinic acetals to form the corresponding cycloadducts in good yields with good endo selectivities.     

A density functional theory study of the enantioselective reduction of prochiral ketones promoted by chiral spiroborate esters

Recently, chiral spiroborate ester [(R)‐2‐((1,3,2‐dioxaborolan‐2‐yloxy)methyl)pyrrolidine] has been experimentally employed as an effective chiral catalyst in the borane‐mediated asymmetric reduction of prochiral ketones to produce the corresponding secondary alcohols. In this article, we have theoretically investigated the mechanism of the reduction using density functional theory. The results reveal that this reaction is accomplished via four steps. Fully geometry optimized reactants, products, transition states, and intermediates were obtained at the B3LYP/6‐31G (d, p) level. The analysis of these results reveals one pathway that is more energetically favorable, and its associated geometries correlate well with the final products of the reaction. The further calculations show that the solvent effect of THF has no great influence on enantioselectivity of this reduction. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

A density functional theory study on mechanism and substituent effects of a base-free and catalyst-free synthesis of functionalized dihydrobenzoxazoles

The reaction mechanism and the substituent effects of a base-free and catalyst-free synthesis of functionalized dihydrobenzoxazole have been investigated in detail by using the density functional theory (DFT) method. The calculated results reveal that the whole reaction should occur through three processes, and the initial intramolecular nucleophilic attack reaction is the rate-determining step. The possibility to afford crossover reaction products has been carefully excluded based on the extremely high barrier, which is well-consistent with the experimental results that the crossover products cannot be observed. The substituent effects have been studied through exploring the correlation of the experimental yields and the theoretically predicted barriers, which proves that the more electron-donating substituents of the imine should be more beneficial to the occurrence of the reaction.     

Unusual coupling reactions of aldehydes and alkynes: a novel preparation of substituted phthalic acid derivatives by automated synthesis

Based upon a highly versatile multicomponent methodology, a new one-pot synthesis of substituted phthalic acid derivatives from alpha,beta-unsaturated aldehydes was developed. The reaction involves the intermediacy of an acetamidodiene species which undergoes Diels-Alder addition to diethyl acetylenedicarboxylate. The resultant acetamidocyclohexadiene is subject to elimination of acetamide under the reaction conditions to give rise to substituted diethyl phthalates in good yields. This domino condensation-cycloaddition-elimination sequence has been applied to a variety of alpha,beta-unsaturated aldehydes. Furthermore, we demonstrated the exploitation of parallelized and automated synthesis technology for the rapid screening of reaction conditions and compositions. Detailed studies revealed the catalytic role of the employed acetamide and the occurrence of a stereoselective 1,4-syn elimination pathway under standard conditions.     

Enantioselective [4+2]-cycloaddition reaction of a photochemically generated o-quinodimethane: mechanistic details, association studies, and pressure effects

1,2,3,4-Tetrahydro-2-oxoquinoline-5-aldehyde (2) was prepared from m-aminobenzoic acid and 3-ethoxyacryloyl chloride (4) in 19 % overall yield. Compound 2 underwent a photochemically induced [4+2]-cycloaddition reaction with various dienophiles upon irradiation in toluene solution. The exo product 10 a was obtained with acrylonitrile (9 a) as the dienophile, whereas methyl acrylate (9 b) and dimethyl fumarate (9 c) furnished the endo products 11 b and 11 c (69-77 % yield). The reactions proceeded at -60 degrees C in the presence of the chiral complexing agent 1 (1.2 equiv) with excellent enantioselectivity (91-94 % ee). The enantiomeric excess increases in the course of the photocycloaddition as a result of the lower product association to 1. The intermediate (E)-dienol 8 was spectroscopically detected at -196 degrees C in an EPA (diethyl ether/isopentane/ethanol) glass matrix. The association of the substrate 2 to the complexing agent 1 was studied by circular dichroism (CD) titration. The measured association constant (K(A)) was 589 M(-1) at room temperature (25 degrees C) and normal pressure (0.1 MPa). An increase in pressure led to an increased association. At 400 MPa the measured value of K(A) was 703 M(-1). Despite the stronger association the enantioselectivity of the reaction decreased with increasing pressure. At 25 degrees C the enantiomeric excess for the enantioselective reaction 2 + 9 a-->10 a decreased from 68 % ee at 0.1 MPa to 58 % ee at 350 MPa. This surprising behavior is explained by different activation volumes for the diastereomeric transition states leading to 10 a and ent-10 a.     

Regio- and stereoisomeric composition of the product mixture in the Diels–Alder reaction of dicyclopentadiene with bicyclononadiene: a NMR and DFT quantum chemical investigation

The regio- and stereoisomeric composition of the product mixture in the Diels–Alder reaction between dicyclopentadiene and bicyclononadiene is determined by 2D ¹H–¹³C HMQC and HMBC and ¹H 2D DQF COSY and NOESY NMR techniques. The absence in the experimental mixture of one of the expected products is explained by high-level quantum chemical density functional theory calculations.     

Reaction energetics on long‐range corrected density functional theory: Diels–Alder reactions

The possibility of quantitative reaction analysis on the orbital energies of long‐range corrected density functional theory (LC‐DFT) is presented. First, we calculated the Diels–Alder reaction enthalpies that have been poorly given by conventional functionals including B3LYP functional. As a result, it is found that the long‐range correction drastically improves the reaction enthalpies. The barrier height energies were also computed for these reactions. Consequently, we found that dispersion correlation correction is also crucial to give accurate barrier height energies. It is, therefore, concluded that both long‐range exchange interactions and dispersion correlations are essentially required in conventional functionals to investigate Diels–Alder reactions quantitatively. After confirming that LC‐DFT accurately reproduces the orbital energies of the reactant and product molecules of the Diels–Alder reactions, the global hardness responses, the halves of highest occupied molecular orbital (HOMO)‐lowest unoccupied molecular orbital (LUMO) energy gaps, along the intrinsic reaction coordinates of two Diels–Alder reactions were computed. We noticed that LC‐DFT results satisfy the maximum hardness rule for overall reaction paths while conventional functionals violate this rule on the reaction pathways. Furthermore, our results also show that the HOMO‐LUMO gap variations are close to the reaction enthalpies for these Diels–Alder reactions. Based on these results, we foresee quantitative reaction analysis on the orbital energies. © 2012 Wiley Periodicals, Inc.     

Variational transition state theory rate constants and H/D kinetic isotope effects for CH3 + CH3OCOH reactions

The rate constants and H/D kinetic isotope effect for hydrogen abstraction reactions involving isotopomers of methyl formate by methyl radical are computed employing methods of the variational transition state theory (VTST) with multidimensional tunneling corrections. The energy paths were built with a dual-level method using the moller plesset second-order perturbation theory (MP2) method as the low-level and complete basis set (CBS) extrapolation as the high-level energy method. Benchmark calculations with the CBS_D-T approach give an enthalpy of reaction at 0 K for R1 (−4.5 kcal/mol) and R2 (−4.2 kcal/mol) which are in good agreement with the experiment, that is, −4.0 and − 4.8 kcal/mol. For the reactional paths involving the isotopomers CH₃ + CH₃OCOH → CH₄ + CH₃OCO and CH₃ + CH₃OCOD → CH₃D + CH₃OCO, the value of k^H/k^D (T = 455 K) using the canonical VTST/small-curvature tunneling approximation method is 6.7 in close agreement with experimental value (6.2). © 2019 Wiley Periodicals, Inc.