Polar Diels-Alder Reactions Research Articles

Why Do Five-Membered Heterocyclic Compounds Sometimes Not Participate in Polar Diels–Alder Reactions?

The reactions of bicyclic enone (BCE, 1) with cyclopentadiene (Cp, 2) and the five-membered heterocyclic compounds (FHCs) furan 3 and N-methyl pyrrole 4 for the construction of polycyclic heterocyclic compounds have been studied at the B3LYP/6-31G* level. No reaction takes place in the absence of Lewis acid (LA) catalysts as a consequence of the high activation energy associated with these reactions. Electrophilic activation of BCE 1 by formation of a complex with the BF3 LA, 1-BF3, and solvent effects favor the reactions. However, a different reactivity is manifested by Cp 2 and FHCs 3 and 4. Thus, while the reaction of 1-BF3 with Cp 2 yields the expected exo [4 + 2] cycloadduct, the reactions of these FHCs yield Michael adducts. In any case, the reactions are characterized by the nucleophilic/electrophilic interaction between the most nucleophilic centers of these dienes and the most electrophilic center of complex 1-BF3. The greater ability of FHCs 3 and 4 to stabilize positive charges opposed to Cp 2 favors a stepwise mechanism with formation of a zwitterionic intermediate. Although in most stepwise Diels-Alder reactions, the subsequent ring closure has unappreciable barriers, in these FHCs the abstraction of a proton with regeneration of the aromatic ring becomes competitive. Thermodynamic calculations suggest that the exergonic character of the formation of the Michael adducts could be the driving force for the reactions involving FHCs.

Experimental and theoretical studies on polar Diels–Alder reactions of 1-nitronaphathalene developed in ionic liquids

The reactions between 1-nitronaphthalene 1 and two nucleophilic dienes, Danishefskýs diene 2 and 1-trimethylsilyloxy-1,3-butadiene 3, to yield phenanthrenols 7 and 8 developed in protic and aprotic ionic liquids (ILs) with an imidazolium cation base permit to conclude that the reactions occur in better experimental conditions than in molecular solvents. The yields obtained with protic ILs are better than those observed with aprotic ILs. In this sense, the higher yields obtained with aprotic ILs, (working at 60 °C, 48 h) are comparable with the lower yields observed in protic ILs (60 °C, 24 h). DFT calculations for the reaction of 1-nitronaphthalene 1 with diene 3, in the absence and in the presence of tetrafluoroborate of 1-metilimidazolium [HMIM][BF4] as protic ILs, indicate that this reaction is a domino process that comprises two consecutive processes: i) a polar Diels–Alder (P-DA) reaction between 1 and 3, and ii) an elimination of nitroso acid 5 to yield dihydrophenanthrene 11. Thermodynamic calculations indicate that while the first reaction is the rate-determining step of this domino process, the nitroso acid elimination is the driving force responsible for the formation of dihydrophenanthrene 11. Implicit and explicit solvent effects indicate that while the hydrogen bond formation between HMIM and one oxygen atom of the nitro groups favour the two reactions, implicit solvent effects modelled by PCM decelerate the P-DA reaction by a large solvation of reagents. Finally, DFT analysis of reagents offers an explanation of the catalytic role of protic ILs in these P-DA reactions.

Polar Diels-Alder Reactions Developed in a Protic Ionic Liquid: 3-Nitroindole as Dienophile. Theoretical Studies Using DFT Methods

N-Tosyl-3-nitroindole reacts with moderate and strong nucleophilic dienes in a polar Diels-Alder reaction using protic ionic liquid (PIL) [HMIM][BF4] as reaction media. In the cases in which the diene has oxygenated substituents, the PIL favors the aromatization of the formal [4+2] cycloadducts. Although the presence of the PIL in the reactions of Ntosyl- 3-nitroindole as electrophile shows a clear tendency to the aromatization of the [4+2] cycloadducts, we observed that the neoteric solvent did not increase the yields in relation to a molecular solvent. Part of this work is specifically concerned with theoretical studies using DFT reactivity indices. The global and local electrophilicity and nucleophilicity indices were calculated for N-tosyl-3-nitroindole, and the dienes used in this study. For the studied reactions, the regioselectivity involved in the polar Diels-Alder reaction is well predicted. Keywords: Dienophile, Diels-Alder, nitroindole, protic ionic liquid

Ionic liquids and microwave irradiation as synergistic combination for polar Diels–Alder reactions using properly substituted heterocycles as dienophiles. A DFT study related

For the DA reactions between nitropyrrole derivatives and isoprene, the combination of microwave irradiation and protic ionic liquids, has a notable synergistic effect. DFT calculations suggest that a supplementary energy ranking in the IR region of 1.700–1400cm−1 can favour the structural changes in the reactants to reach the TS.

Origin of the synchronicity in bond formation in polar Diels–Alder reactions: an ELF analysis of the reaction between cyclopentadiene and tetracyanoethylene

The origin of the synchronicity in C-C bond formation in polar Diels-Alder (P-DA) reactions involving symmetrically substituted electrophilic ethylenes has been studied by an ELF analysis of the electron reorganization along the P-DA reaction of cyclopentadiene (Cp) with tetracyanoethylene (TCE) at the B3LYP/6-31G* level. The present study makes it possible to establish that the synchronicity in C-C bond formation in P-DA reactions is controlled by the symmetric distribution of the electron-density excess reached in the electrophile through the charge transfer process, which can be anticipated by an analysis of the spin electron-density at the corresponding radical anion. The ELF comparative analysis of bonding along the DA reactions of Cp with ethylene and with TCE asserts that these DA reactions, which have a symmetric electron reorganization, do not have a cyclic electron reorganization as the pericyclic mechanism states. Due to the very limited number of cases of symmetrically substituted ethylenes, we can conclude that the synchronous mechanism is an exception of DA reactions.

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.

HDA cycloadditions of 1-diethoxyphosphonyl-1,3-butadiene with nitroso heterodienophiles: A computational investigation

The hetero Diels–Alder (HDA) reactions of 1-diethoxyphosphonyl-1,3-butadiene with various nitroso dienophiles have been studied at the B3LYP/6-31G∗∗ level. Structural, energetic and electronic properties are discussed. These cycloadditions with nitroso dienophiles are characterized by a total proximal regioselectivity and an endo selectivity. The influence of the nitroso substitution on the activation barrier and the regiochemistry of the reaction is presented. The analysis of the chemical rearrangement along the intrinsic reaction pathway (IRC), based on bond order and on natural bond orbital (NBO) calculations, emphasizes the polar nature of these cycloadditions. Despite the early and the cyclic nature of the corresponding transition states, a two-center interaction governs this mechanism: these cycloadditions are Polar Diels–Alder reactions (P-DA).

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 mechanism of polar Diels–Alder reactions

A good correlation between the activation energy and the polar character of Diels-Alder reactions measured as the charge transfer at the transition state structure has been found. This electronic parameter controls the reaction rate to an even greater extent than other recognized structural features. The proposed polar mechanism, which is characterized by the electrophilic/nucleophilic interactions at the transition state structure, can be easily predicted by analyzing the electrophilicity/nucleophilicity indices defined within the conceptual density functional theory. Due to the significance of the polarity of the reaction, Diels-Alder reactions should be classified as non-polar (N), polar (P), and ionic (I).

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.

ChemInform Abstract: Behavior of Selenophenes Substituted with Electron‐Withdrawing Groups in Polar Diels—Alder Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Mechanistic details of the domino reaction of nitronaphthalenes with the electron-rich dienes. A DFT study

The reaction of 1-nitronaphthalene ( 1) with the Danishefsky diene ( 2) to give the dihydrophenanthrene derivative 11 has been theoretically studied using DFT methods. This reaction is a domino process that is initialized by a polar Diels–Alder reaction between 1 and 2 to give the formally [2 + 4] cycloadduct 3. The subsequent concerted elimination of nitrous acid ( 4) from 3 yields 11. Analysis of the global reactivity indices as well as the thermodynamic data for this domino process indicate that while the large electrophilic character of 1 together with the large nucleophilic character of 2 are responsible for the participation of these reagents in a polar Diels–Alder reaction, the irreversible extrusion of 4 is the factor responsible for the feasibility of the overall process.

Behaviour of selenophenes substituted with electron-withdrawing groups in polar Diels–Alder reactions

The normal electron-demand Diels–Alder reactions between substituted selenophenes, nitro being one of these groups, and dienes of diverse reactivity give benzoselenophenes derivatives.

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.

Towards an Understanding of the Polar Diels–Alder Reactions of Nitrosoalkenes with Enamines: A Theoretical Study

AbstractThe polar Diels–Alder reactions of nitrosoalkenes with enamines have been studied using DFT methods at the B3LYP/6‐31G* level of theory. These Diels–Alder reactions are characterized by a nucleophilic attack of the enamine at the conjugated position of the nitrosoalkene with concomitant ring‐closure. The reactions present a total regioselectivity and a largeendoselectivity. The analysis, based on the global electrophilicity of the reagents in the ground state, the natural bond orbital (NBO), and the topological analysis of the electron localization function (ELF) in theendotransition state (TS) and “halfway” along the IRC between the TS and cycloadduct, correctly explain the polar nature of these cycloaddition reactions. The large electrophilic character of nitrosoethylenes together with the large nucleophilic character of enamines are responsible for the large acceleration found in these polar Diels–Alder reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

A DFT study of the polar Diels–Alder reaction between 4-aza-6-nitrobenzofuroxan and cyclopentadiene

The polar Diels–Alder reaction between 4-aza-6-nitrobenzofuroxan (ANBF) and cyclopentadiene has been studied using DFT procedures at the B3LYP/6-31G* level. Only one highly asynchronous transition state structure associated to the formation of the [4+2] adduct 13 is found. A further [3,3] sigmatropic shift on the [4+2] cycloadduct 13 allows its conversion into the thermodynamically more stable [2+4] cycloadduct 14 . The analysis of the global and local electrophilicities of the reagents correctly explain the behaviour of ANBF as a strong electrophile in polar cycloadditions.

Origin of the Synchronicity on the Transition Structures of Polar Diels—Alder Reactions. Are these Reactions [4 + 2] Processes?

The transition structures (TSs) for a series of related Diels−Alder reactions between cyclopentadiene and mono-, di-, tri-, and tetracyanoethylene derivatives have been studied with use of DFT meth...