- Reversible Diels-Alder reactions for the generation of dynamic combinatorial libraries
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(Chemical Equation Presented) Condensation reactions between various dienes and dienophiles have been screened for reversibility. Functionalized fulvenes, bearing in particular biological groups, and cyanolefins have been found to react rapidly and reversibly, in the temperature range from -10 to +50°C. These results pave the way for the development of dynamic combinatorial libraries based on reversible Diels-Alder chemistry.
- Boul, Peter J.,Reutenauer, Philippe,Lehn, Jean-Marie
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- Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene with 6,6-dimethylfulvene: Cycloadditions and a rearrangement
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Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene (BTF;1) with 6,6-dimethylfulvene (2) affords the expected Diels-Alder cycloadduct, 7-(1-methylethylidene)-3,3-bis(trifluoromethyl)bicyclo[2.2.1]- hept-5-ene-2,2-dicarbonitrile (3), in good yield. The cycloadduct 3 is unstable and exists in equilibrium with the starting materials in less polar solvents. In more polar environment, the [4 + 2] adduct 3 either reverts to starting materials, or, in a competing process, is converted to the formal [2 + 2] adduct, 2-(1-methylethylidene)-7,7- bis(trifluoromethyl)bicyclo[3.2.0]hept-3-ene-6,6-dicarbonitrile (6). In the presence of acid, 3 is converted to a third isomeric form, 1,3a,5,6-tetrahydro- 7-methyl-5,5-bis(trifluoromethyl)-4H-indene-4,4-dicarbonitrile (8). Both 6 and 8 are formed with complete regiospecificity. Quantum mechanical calculations and X-ray crystallographic studies of this ensemble of reactions by BTF, and the analogous set of reactions by its progenitor, tetracyanoethylene (TCNE), reveal several interesting facets. The conversion of 3 to 6 occurs in certain polar solvents, in the presence of silica gel and alumina, as well as in the solid state. Single crystals of 3 were observed by X-ray crystallography to undergo crystal-to-crystal rearrangement to 6. The conversion of 3 to 8 proceeds by the initial retro-Diels -Alder reaction followed by isomerization of the fulvene to 1-isopropenyl-1,3-cyclopentadiene that then reacts with BTF to give the alternative Diels-Alder product as a single regioisomer. A hybrid density functional theory (DFT) method at the B3LYP/6-31G(d) level of theory gave calculated relative energies of 0.0, -9.0, and -18.8 kcal/mol for 3, 6, and 8, respectively. The same method was also used to correctly predict the regiochemical outcome of the cycloaddition of BTF with 1-isopropenyl-1,3-cyclopentadiene. Finally, an explanation is offered for the preference of the persubstituted cyanoolefins BTF and TCNE to add to the exocyclic diene portion of 1-isopropenyl-1,3-cyclopentadiene and the contrasting preference of 2-acetyloxy-2-propenenitrile to add to the endocyclic diene.
- Howard, Michael H.,Alexander,Marshall, William J.,Roe, D. Christopher,Zheng
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p. 120 - 129
(2007/10/03)
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- The effect of pressure on retro Diels-Alder reactions
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The activation and reaction volumes (ΔV(≠)/ΔV) were determined for the retro Diels-Alder reactions of the parent dihydrobarrelene 1a, its 2- cyano derivative 1b, the exo and endo Diels-Alder adducts of maleic anhydride to naphthalene exo-, endo-4, and the exo and endo Dies-Alder adducts of N- phenylmaleic imide to 6,6-dimethylfulvene exo-, endo-8 from the pressure dependence of the rate constants and the partial molar volumes (V) of reactants and products at various temperatures. The cleavage of exo-4, endo- 4, and exo-8 are slightly accelerated by pressure showing negative volumes of activation (V(≠) 0). From the analysis of the volume data including the van der Waals volumes (V(w)) one can conclude that the packing coefficients of the pericyclic transition states are equal to or even larger than those of the corresponding Diels-Alder adducts. This finding may be explained with the restriction of the degrees of freedom in the transition states leading to a contraction of the expansion volume.
- Klaerner, Frank-Gerrit,Breitkopf, Volker
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p. 2757 - 2762
(2007/10/03)
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- Rearrangement and Cycloreversion of Diels-Alder Adducts of Cyclic 1,3-Dienes to Norbornadienes. A Novel homo-Cope Rearrangement. Evidence for Competitive Pericyclic and Diradical Processes
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On thermolysis of endo,endo-5, endo,endo-17, and endo,exo-17 ( the endo,endo and endo,exo Diels-Alder adducts of cyclopentadiene 7 or dimethylfulvene 15 to norbornadiene 8 or 7-isopropylidenenorbornadiene 20), a novel type of homo-Cope rearrangement leading to 6, 21, and 23a, respectively, competes with the retro-Diels-Alder reactions.According to a force-field analysis of the kinetic parameters, the competitive reactions (rearrangement and retro-Diels-Alder reaction) of endo,endo-5 occur in a pericyclic fashion whereas in the isopropylidene-substituted systems stepwise processes compete with the corresponding pericyclic reactions.Indirect experimental evidence for this assumption comes from a stereochemical analysis of the retro-Diels-Alder reaction in the cis-5,6-dideuterionorbornene derivatives exo-36-d2, endo-36-d2 and exo-39-d2, endo-39-d2 occuring stereospecifically in the case of exo-36-d2, endo-36-d2 and non-stereospecifically in the case of exo-39-d2, endo-39-d2.The change in mechanism rationalized by a different (allyl vs. pentadienyl) stabilization of the potential diradical intermediates in the stepwise reactions. - Key Words: Kinetic parameters / Stepwise and pericyclic reactions / Calculations, force field / Calculations of transition-state resonance energy (energy of concert)
- Hochstrate, Dirk,Klaerner, Frank-Gerrit
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p. 745 - 754
(2007/10/02)
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- Carbene Reactions, XVIII. Thermal Behaviour of 7-Alkylidenebicycloheptadiene Derivatives
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Thermolysis of 7-alkylidenenorbornadienes 2 results in a retro-Diels-Alder cleavage to fulvenes and acetylene.A different mode of cleavage - into benzene and a carbene - is observed with such derivatives of 2 which carry ?- or ?-donor functions at C-8.The dependence of the reaction pathways on the nature of the substituent at C-8 is discussed on the basis of MO-calculations.
- Hoffmann, Reinhard W.,Riemann, Achim,Mayer, Bernhard
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p. 2493 - 2513
(2007/10/02)
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- SITE SELECTIVITY IN THE REACTIONS OF 1,3-DIPOLES WITH NORBORNADIENE DERIVATIVES
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The cycloadditions of arylazides, benzonitrile oxides and diphenylnitrile imine to norbornadiene derivatives 1a-c showed varying degree of site- and stereo-selectivity.With dipolarophile 1a arylazides and benzonitrile oxides attack, preferentially, the electron-poor tetrasubstituted double bond, while in the case of 1b and 1c is the substituted double bond which enters the cycloaddition.By contrast, 2-diazopropane and C-phenyl-N-methylnitrone react with the sole tetrasubstituted double bond of 1a-c in stereo- and site-specific cycloadditions.The quantitative evaluation of the two possible reaction paths was performed by glc analysis.The compounds detected were those arising from Diels-Alder cycloreversions of the thermally labile intermediate adducts 2 and 3 (Scheme 1).The results were rationalized on the basis of a qualitative perturbation treatment which considers frontier orbital interactions only.
- Cristina, D.,Amici, M. De,Micheli, C. De,Gandolfi, R.
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p. 1349 - 1357
(2007/10/02)
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