Polar Diels-Alder Research Articles

Diels–Alder reactions for the rational design of benzo[b]thiophenes: DFT-based guidelines for synthetic chemists

Abstract In this work we studied the capability of several diene/dienophile pairs to undergo Diels–Alder (DA) reactions leading to benzo[ b ]thiophenes. A variety of synthetically and commercially available nitrothiophenes were chosen as dienophiles. Methyl 5-nitro-3-thiophenecarboxylate was selected as a potential strong electrophilic candidate based on some DFT-based properties and the substitution pattern of the expected product. The mechanistic details concerning the participation of this dienophile in polar DA reactions were investigated through a theoretical point of view. The results were compared with the experimental outcomes. This methodology should allow synthetic chemists to analyze DA reactions in detail in a stage prior to the synthetic job.

Theoretical Analysis of Substituted Diels - Alder Reagents to Determine the Polar or Non Polar Character of the Reaction

The non-polar character of Diels – Alder (DA) reactions using 1- and 2-substituted butadienes and ethylene is discussed. Linear correlations between variations in the energy barrier and the electrophilicity index have been obtained. The charge transfer (CT) process in the cycloaddition reactions depends on the substitution pattern on almost all ethylene reagents. The current work stresses that a polar DA reaction will occur when only the ethylene is substituted by electronwithdrawing (EW) groups increasing its electrophilicity or when both DA reagents are being activated by EW and electron-releasing (ER) groups, enhancing their electrophilic and nucleophilic nature. Keywords: Polar Diels-Alder reactions, non polar Diels-Alder reactions, substituted butadienes and ethylenes, electrophilicity, nucleophilicity, dienophile, 1,3-dipolar cycloaddition, regioselectivity, tetracyanoethylene, Guassian03

Elucidation of the Chemo- and Regioselectivity of Polar Diels-Alder Reactions involving Thiophene-1, 1-Dioxides Using DFT-Based Reactivity Indexes

The analysis of the global electrophilicity indexes of some substituted thiophene-1,1- dioxides shows that these species act as potential electrophiles in polar Diels – Alder reactions with diene systems. The chemo- and regioselectivity of these cycloadditions are rationalized using local electrophilicity and local nucleophilicity indexes recently proposed by Domingos group [Domingo, L. R.; Aurell, M. J.; Perez, P.; Contreras, R. Quantitative Characterization of the Local Electrophilicity of Organic Molecules. Understanding the Regioselectivity on Diels Alder Reactions. J. Phys. Chem. A., 2002, 106(29), 6871-6875; Perez, P.; Domingo, L. R.; Duque-Norena, M.; Chamorro, E. A Condensed-to-Atom Nucleophilicity Index. An Application to the Director Effects on the Electrophilic Aromatic Substitutions. J. Mol. Struct. THEOCHEM, 2009, 895, 86-91]. The cyclization modes, predicted using these static DFT-based reactivity indexes, are in good agreement with experimental outcomes.

The Participation of 2H‐Pyran‐2‐ones in [4+2] Cycloadditions: An Experimental and Computational Study

AbstractExperimental and computational DFT studies of the Diels–Alder (DA) reaction mechanism for the series of 2H‐pyran‐2‐ones 1 and non‐symmetrically substituted alkynes 2, 10, and 11 were undertaken. Several 2H‐pyran‐2‐ones 1 were treated with N,N‐diethylpropynamine (2). The results point toward a polar and asynchronous two‐step mechanism that is in line with the characteristics of a polar Diels–Alder (P‐DA) reaction mechanism.5 Unexpected formation of minor products 4a–d during the reaction of 1 with 2 can be rationalized by considering the easily passable torsion barrier around the newly formed C–C bond that enables two different cyclization modes. The charge transfer (CT) and global reactivity indices analyses demonstrated that in these reactions 2H‐pyran‐2‐ones act as electrophiles and N,N‐diethylpropynamine (2) acts as a nucleophile reaction partner. The introduction of electron‐withdrawing carboxylic substituents on the dienophiles 10 and 11 shifts the DA reaction with 2H‐pyran‐2‐ones to a less polar and more synchronous concerted reaction mechanism. Calculated CT as well as values of the global electrophilicity and nucleophilicity N indexes revealed that 2H‐pyran‐2‐ones act in this case as nucleophiles and reacting dienophiles 10 and 11 as electrophiles. The results are consistent with the experimental data and kinetic analyses, thus providing valuable insights into 2H‐pyran‐2‐one chemistry and paving the way for an efficient synthesis of highly functionalized benzene derivatives as well as broadening the mechanistic understanding of these highly versatile reactions.

Theoretical Study on the Reaction Mechanism between 6-Benzyl-6-azabicyclo[2.2.1]hept-2-ene and Benzoyl Isocyanate to Urea and Isourea

Reaction mechanisms of the 6-benzyl-6-azabicyclo[2.2.1]hept-2-ene with benzoyl isocyanate have been investigated using density functional theory (DFT) at the B3LYP/6-31G(d,p) level of theory. The reaction proceeding along six competitive channels includes two categories. That is, two channels are formally [3,3]-sigmatropic rearrangements and four channels are [4+2] cycloadditions. For urea, the formally [3,3]-sigmatropic rearrangement channel and the [4+2] cycloaddition channels are competitive since they have similar barriers. However, the [4+2] cycloaddition channels are energetically favorable pathways to lead to isourea, with the highest barrier of 12.77 kcal/mol. These polar Diels-Alder (P-DA) reactions are controlled by the charge transfer (CT) at the transition states. Moreover, the main products of this reaction include urea and isourea. Furthermore, difference of two new bond lengths at transition states indicate that the [4+2] cycloadditions in this reaction are asynchronous processes, which is in good agreement with the experiment.

Theoretical Evaluation of Global and Local Electrophilicity Patterns to Characterize Hetero-Diels−Alder Cycloaddition of Three-Membered 2H-Azirine Ring System

Present communication elicits an interesting interaction between 2H-azirine and a number of electron rich and electron deficient dienes. A series of substituted 2H-azirine 1-10, and three dienes namely cyclopentadiene D-1, furfural D-2, and dinitrofuran D-3 were chosen to investigate and critically review the reactivity and selectivity of Diels-Alder cycloaddition strategy. The global and local electrophilicity patterns have been evaluated to interpret the electrophilic/nucleophilic behavior of dienes D-1 to D-3 and dienophiles 1-10, in polar Diels-Alder cycloaddition, using the DFT method at the B3LYP/6-31G* level of theory. Regional nucleophilicity have been evaluated using local nucleophilicity descriptor N(k) (Perez, P.; Domingo, L. R.; Duque-Norena, M.; Chamorro, E. J. Mol. Struct. THEOCHEM 2009, 895, 86-91), and regional electrophilicity at the active sites of the interactive species involved in Diels-Alder processes have been described on a quantitative basis using local electrophilicity index omega(k).

Forced Cough Equals Local Anesthesia for Cervical Biopsy

The behaviors of N-tosylnitropyrroles acting as electrophilic dienophiles in polar Diels-Alder reactions joint to different dienes of increeased nucleophilicity are analyzed. The reactions were developed under microwave irradiation using toluene or protic ionic liquids (PILs) as solvents and in free solvent conditions. In all the cases explored we observed good yields in short reaction times. For these reactions, the free solvent condition and the use of protic ionic liquids as solvents offer similar results. However, the free solvent conditions favor environmental sustainability. The role of PILs in these polar Diels-Alder reactions has been theoretically studied within the Molecular Electron Density Theory.

Understanding the stereo‐ and regioselectivities of the polar Diels–Alder reactions between 2‐acetyl‐1,4‐benzoquinone and methyl substituted 1,3‐butadienes: a DFT study

AbstractThe polar Diels–Alder (DA) reactions of 2‐acetyl‐1,4‐benzoquinone (acBQ) with methyl substituted 1,3‐butadienes have been studied using DFT methods at the B3LYP/6‐31G(d) level of theory. These reactions are characterized by a nucleophilic attack of the unsubstituted ends of the 1,3‐dienes to the β conjugated position of the acBQ followed by ring‐closure. The reactions present a total regioselectivity and large endo selectivity. The analysis based on the global electrophilicity of the reagents at the ground state, and the natural bond orbital (NBO) population analysis at the transition states correctly explain the polar nature of these cycloadditions. The large electrophilic character of acBQ is responsible for the acceleration observed in these polar DA reactions. Copyright © 2008 John Wiley & Sons, Ltd.

An Understanding of the Electrophilic/Nucleophilic Behavior of Electro-Deficient 2,3-Disubstituted 1,3-Butadienes in Polar Diels−Alder Reactions. A Density Functional Theory Study

The electrophilic/nucleophilic behavior of dimethyl 2,3-dimethylenesuccinate 1, an electron-deficient 2,3-disubstituted 1,3-butadiene, in polar Diels-Alder reactions has been studied using DFT methods at the B3LYP/6-31G(d) level of theory. The electronic nature of bonding of the transition structures involved in the cycloaddition reactions of the diene 1 toward the nucleophilically activated dienophile 6 and the strong electrophilically activated dienophile 7 has been carefully examined within the natural bond orbital (NBO) and the topological analysis of the electron localization function (ELF) frameworks. Additionally, a study of the global electrophilicity pattern of the reagents at the ground state was performed. This evidence allows us to rationalize the participation of electron-deficient 2-susbtituted and 2,3-disubstituted 1,3-butadienes as nucleophiles in polar Diels-Alder reactions.

Hydrogen bonding catalysis operates by charge stabilization in highly polar Diels-Alder reactions.

[reaction: see text] The alcohol-catalyzed Diels-Alder reactions of acrolein and benzaldehyde with Rawal's diene were evaluated with density functional theory (B3LYP/6-31G(d)). Several potential modes of catalysis with two methanol molecules were used to model catalysis by TADDOLs. In agreement with crystallographic data, cooperative catalysis with TADDOLs is predicted to be favorable.