Diels-Alder reaction derivatives

An intense purple crystalline solid m.p. 219-220 C. One of the few monomeric cyclo-pentadienone derivatives, most of which spontaneously undergo self Diels-Alder type dimerization. Used as a diene in many studies of various aspects of the Diels-Alder reaction. ... 

Diederich F, Jonas U, Gramlich V, Herrmann A, Ringsdorf H and Thilgen C 1993 Synthesis of a fullerene derivative of benzo[18]crown-6 by Diels-Alder reaction complexation ability, amphiphilic properties, and x-ray crystal structure of a dimethoxy-1,9-(methano[1, 2]benzomethano)fullerene[60] benzene clathrate Helv. Chim. Acta 76 2445-53... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

Fortunately, azachalcone derivatives (2.4a-g, Scheme 2.4) turned out to be extremely suitable dienophiles for Lewis-add catalysed Diels-Alder reactions with cyclopentadiene (2.5). This reaction is outlined in Scheme 2.4 and a large part of this thesis will be devoted to the mechanistic details of this process. The presence of a chromophore in 2.4 allows kinetic studies as well as complexation studies by means of UV-vis spectroscopy. Furthermore, the reactivity of 2.4 is such that also the... 

Interestingly, G jrey et al.", employing a similar tryptophan-derived catalyst (3.4), observed a 99% enantiomeric excess (ee) in the Diels-Alder reaction of 2-bromoacrolein with cyclopentadiene... 

Chapter 5, may provide a rationale. Conclusions derived from a number of H-MVIR measurements indicate that cyclopentadiene has a high affinity for the interior of the micelles that were investigated, whereas the dienophile prefers the outer regions. In view of the structures of most dienes and dienophiles such a spatial separation can be expected for the majority of Diels-Alder reactions. This arrangement accounts for the unexpectedly small influence of micelles on the rates of Diels-Alder reactions as reported in the literature. 

In contrast to SDS, CTAB and C12E7, CufDSjz micelles catalyse the Diels-Alder reaction between 1 and 2 with enzyme-like efficiency, leading to rate enhancements up to 1.8-10 compared to the reaction in acetonitrile. This results primarily from the essentially complete complexation off to the copper ions at the micellar surface. Comparison of the partition coefficients of 2 over the water phase and the micellar pseudophase, as derived from kinetic analysis using the pseudophase model, reveals a higher affinity of 2 for Cu(DS)2 than for SDS and CTAB. The inhibitory effect resulting from spatial separation of la-g and 2 is likely to be at least less pronoimced for Cu(DS)2 than for the other surfactants. 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

Cyclohexene derivatives can be oxidatively cleaved under mild conditions to give 1,6-dicarbonyl compounds. The synthetic importance of the Diels-Alder reaction described above originates to some extent from this fact, and therefore this oxidation reaction is discussed in this part of the book. 

In antithetical analyses of carbon skeletons the synthon approach described in chapter I is used in the reverse order, e.g. 1,3-difunctional target molecules are "transformed" by imaginary retro-aldol type reactions, cyclohexene derivatives by imaginary relro-Diels-Alder reactions. 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

Section 10 12 Conjugate addition of an alkene (the dienophile) to a conjugated diene gives a cyclohexene derivative in a process called the Diels-Alder reaction It is concerted and stereospecific substituents that are cis to each other on the dienophile remain cis m the product... 

Several Diels-Alder reactions in which acrolein participates as the dienophile are of industrial significance. These reactions involve butadiene or substituted butadienes and yield the corresponding 1,2,5,6-tetrahydroben2aldehyde derivative (THBA) examples are given in Table 9 (90). These products have found use in the epoxy and perfume/fragrance industries. 

Many other acrolein derivatives produced via Diels-Alder reactions are classified as flavors and fragrances. Among those of commercial interest are lyral, (1) [31906-04-4] (91,92) andmyrac aldehyde, C 3H2oO, (2) [80450-04-0] (92,93). 

Diels-Alder Reactions. The important dimerization between 1,3-dienes and a wide variety of dienoplules to produce cyclohexene derivatives was discovered in 1928 by Otto Diels and Kurt Alder. In 1950 they won the Nobel prize for their pioneering work. Butadiene has to be in the j -cis form in order to participate in these concerted reactions. Typical examples of reaction products from the reaction between butadiene and maleic anhydride (1), or cyclopentadiene (2), or itself (3), are <7 -1,2,3,6-tetrahydrophthaHc anhydride [27813-21 -4] 5-vinyl-2-norbomene [3048-64-4], and 4-vinyl-1-cyclohexene [100-40-3], respectively. 

Flame Retardants. Although the use of chlorinated derivatives of DCPD has been restricted in the pesticide area, some are widely used in flame and fire retardant chemicals (see Flame retardants). The starting material is the fliUy chlorinated DCPD cracked to monomeric hexachlorocyclopentadiene, which is then converted via a Diels-Alder reaction with maleic anhydride to a reactive bicycHc anhydride (9), known as chlorendic anhydride [115-27-5]. 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Ring expansion of five- to six-membered rings such as oxazole —> pyridine derivatives via a Diels-Alder reaction is a well-established procedure. However, the conversion of a six-membered heterocycle into a five-membered ring system has not been exploited to any great extent, and those systems that have been studied usually involve a cationic species. 

Diels-Alder reactions, 4, 842 flash vapour phase pyrolysis, 4, 846 reactions with 6-dimethylaminofuKenov, 4, 844 reactions with JV,n-diphenylnitrone, 4, 841 reactions with mesitonitrile oxide, 4, 841 structure, 4, 715, 725 synthesis, 4, 725, 767-769, 930 theoretical methods, 4, 3 tricarbonyl iron complexes, 4, 847 dipole moments, 4, 716 n-directing effect, 4, 44 2,5-disubstituted synthesis, 4, 116-117 from l,3-dithiolylium-4-olates, 6, 826 electrocyclization, 4, 748-750 electron bombardment, 4, 739 electronic deformation, 4, 722-723 electronic structure, 4, 715 electrophilic substitution, 4, 43, 44, 717-719, 751 directing effects, 4, 752-753 fluorescence spectra, 4, 735-736 fluorinated derivatives, 4, 679 H NMR, 4, 731 Friedel-Crafts acylation, 4, 777 with fused six-membered heterocyclic rings, 4, 973-1036 fused small rings structure, 4, 720-721 gas phase UV spectrum, 4, 734 H NMR, 4, 7, 728-731, 939 solvent effects, 4, 730 substituent constants, 4, 731 halo... 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

Other methods for the preparation of cyclohexanecarboxaldehyde include the catalytic hydrogenation of 3-cyclohexene-1-carboxaldehyde, available from the Diels-Alder reaction of butadiene and acrolein, the reduction of cyclohexanecarbonyl chloride by lithium tri-tcrt-butoxy-aluminum hydride,the reduction of iV,A -dimethylcyclohexane-carboxamide with lithium diethoxyaluminum hydride, and the oxidation of the methane-sulfonate of cyclohexylmethanol with dimethyl sulfoxide. The hydrolysis, with simultaneous decarboxylation and rearrangement, of glycidic esters derived from cyclohexanone gives cyclohexanecarboxaldehyde. 

The selection rules for cycloaddition reactions can also be derived from consideration of the aromaticity of the transition state. The transition states for [2tc -f 2tc] and [4tc -1- 2tc] cycloadditions are depicted in Fig. 11.11. For the [4tc-1-2tc] suprafacial-suprafacial cycloaddition, the transition state is aromatic. For [2tc -F 2tc] cycloaddition, the suprafacial-suprafacial mode is antiaromatic, but the suprafacial-antarafacial mode is aromatic. In order to specify the topology of cycloaddition reactions, subscripts are added to the numerical classification. Thus, a Diels-Alder reaction is a [4tc -f 2 ] cycloaddition. The... 

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