Electron deficient ene reactions

A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

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). 

Where we have reason to suspect the involvement of a particular species as a labile intermediate in the course of a reaction, it may be possible to confirm our suspicions by introducing into the reaction mixture, with malice aforethought, a reactive species which we should expect our postulated intermediate to react with particularly readily. It may then be possible to divert the labile intermediate from the main reaction pathway—to trap it—and to isolate a stable species into which it has been unequivocally incorporated. Thus in the hydrolysis of trichloromethane with strong bases cf. p. 46), the highly electron-deficient dichlorocarbene, CClj, which has been suggested as a labile intermediate (p. 267), was trapped by introducing into the reaction mixture the electron-rich species cis but-2-ene (11), and then isolating the resultant stable cyclopropane derivative (12), whose formation can hardly be accounted for in any other way ... 

The bond reorganization process shown in Eq. (1) is formally known as an Alder-ene reaction, where X=H. The classic example involving the thermal reaction of an alkene having allylic hydrogen(s) (an ene) with an electron-deficient unsaturated compound (an enophile) was first reported by Alder in 1943 [1]. 

Electron-deficient olefins, asymmetric epoxidation, 386-91 Electron diffraction dialkyl peroxides, 713 ozonides, 721, 723 1,2,4-trioxolanes, 740 see also Gas electron diffraction Electron-donating substituents ene reactions, 841 sulfonyl peroxides, 1005-7 Electronegative functional groups,... 

The versatility of these [4+2] heterocyclization reactions is a consequence of the wide range of ene and diene components which can be used. In addition to alkenes and alkynes functioning as ene components, a variety of heterodienophiles is available such as electron-deficient imines (e.g. equation 89), nitriles e.g. equation 90), electrophilic carbonyl compounds (e.g. equation 91), thiocarbonyl compounds (e.g. equation 92), singlet oxygen (e.g. equation 93), nitroso compounds (e.g. equation 94), sulfenylsulfonamides (e.g. equation 95) and azo compounds (e.g. equation 96). Many of these reactions proceed with excellent regioselectivity and stereoselectivity, probably because in many instances they involve... 

The maleimide group can undergo a variety of chemical reactions. The reactivity of the double bond is a consequence of the electron withdrawing nature of the two adjacent carbonyl groups which create a very electron-deficient double bond, and therefore is susceptible to homo- and copolymerizations. Such polymerizations may be induced by free radicals or anions. Nucleophiles such as primary and secondary amines, phenates, thiophenates, carboxylates, etc. may react via the classical Michael addition mechanism. The maleimide group furthermore is a very reactive dienophile and can therefore be employed in a variety of Diels Alder reactions. Bisdienes such as divinylbenzene, bis(vinylbenzyl) compounds, bis(propenylphenoxy) compounds and bis(benzocyclobutenes) are very attractive Diels Alder comonomers and therefore some are used as constituents for BMI resin formulations. An important chemical reaction of the maleimide group is the ENE reaction with allylphenyl compounds. The most attractive comonomer of this family is DABA particularly when tough bismaleimide resins are desired. 

Asymmetric ene reactions.1 The reaction of alkenes with prochiral, electron-deficient aldehydes can furnish optically active homoallylic alcohols when catalyzed by ( + )- or (-)-l and in the presence of activated 4-A molecular sieves. In the absence of the sieves, a stoichiometric amount of the organoaluminum complex is essential for high chemical and optical yields. 

Recently, the transition-metal-catalyzed addition of active methylene C-H bonds to electron-deficient olefins having a carbonyl, a nitrile, or a sulfonyl group has been extensively studied by several research groups. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers [88]. Another topic of recent interest is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. In this section, the ruthenium-catalyzed addition of C-H bonds in active methylene compounds to carbonyl groups and C-C multiple bonds is described. 

The HuangMinlon reduction of 3-formylfuran gives 3-methylene-2,3-dihydrofuran. The product undergoes ene reactions with a number of electron-deficient alkenes and provides a route to functionalize the 3-position in furan as shown in Scheme 132. 

Enophiles may include carbonyls, thiocarbonyls, imines, alkenes and alkynes. When the carbonyl is an enophile, the reaction is called a carbonyl ene reaction. The enol form of an unsaturated ketone may serve as an ene in an intermolecular ene reaction known as the Conia-ene reaction. Ene reactions proceed best when the enophilic double bond is electron deficient. Hydrogen is the most common atom transferred in an ene reaction. Other atoms or groups may, however, participate in ene-like transformations. 

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