Electrophilic reactions enophiles

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

Because the enophiles are normally the electrophilic reagent, their reactivity increases with addition of EWG substituents. Ene reactions between unsubstituted alkenes have high-energy barriers, but compounds such as acrylate or propynoate esters... 

Scheme 10.2 gives some examples of ene and carbonyl-ene reactions. Entries 1 and 2 are thermal ene reactions. Entries 3 to 7 are intermolecular ene and carbonyl-ene reactions involving Lewis acid catalysts. Entry 3 is interesting in that it exhibits a significant preference for the terminal double bond. Entry 4 demonstrates the reactivity of methyl propynoate as an enophile. Nonterminal alkenes tend to give cyclobutenes with this reagent combination. The reaction in Entry 5 uses an acetal as the reactant, with an oxonium ion being the electrophilic intermediate. 

This review has attempted to bring together the reactions of ADC compounds which are useful in heterocyclic synthesis, and to develop the general trends that have so far appeared in their reactivity. Thus, in general, ADC compounds are more powerful dienophiles than the corresponding C=C compounds, particularly when the azo bond is in the cis configuration. However, they are also more reactive as enophiles and electrophiles, and may react as such even in cases where Diels-Alder (or other) cycloaddition is formally possible, and where the corresponding C=C compounds do react as dienophiles. Nevertheless, despite this added complication, the major use of ADC compounds has been as dienophiles in the synthesis of pyridazines... 

The carbonyl group in a ketone or aldehyde is an extremely versatile vehicle for the introduction of functionality. Reaction can occur at the carbonyl carbon atom using the carbonyl group as an electrophile or through enolate formation upon removal of an acidic proton at the adjacent carbon atom. Although the carbonyl group is an integral part of the nucleophile, a carbonyl compound can also be considered as an enophile when involved in an asymmetric carbonyl-ene reaction or dienophile in an asymmetric hetero Diels-Alder reaction. These two types of reaction are discussed in the next three chapters. 

Reaction of 3-methyleneindolines with enophiles We have observed that the isomerization of the methyleneindolines 9 to their aromatic methylindoles 2 isomers, did not take place just after the addition of the electrophiles but on the workup or silica gel chromatography of the reaction. Buchwald et al.[17fhi] demonstrated that 3-methylenindolines could un-... 

Ene reactions have relatively high activation energies and intermolecular reaction is observed only for strongly electrophilic enophiles. Some examples are given in Scheme 6.15. 

The major interaction between these two molecules is between the nucleophilic end of the exo-cyclic alkene and the electrophilic end of the acrylate. These atoms have the largest coefficients in the HOMO and LUMO, respectively, and, in the transition state, bond formation between these two will be more advanced than anywhere else. For most ordinary alkenes and enophiles, Lewis acid catalysis to make the enophile more electrophilic, or an intramolecular reaction (or botft is necessary for an efficient ene reaction. 

The intermolecular reaction of 2,3-allenoates with propargyl electrophiles in the presence of catalytic amounts of Pd(ll) affords /3-allenyl A -butenolides, which are reactive enophiles with electron-deficient alkenes (Equation 48)... 

Azo-ene reactions. The ene reaction provides a powerful method for C-C bond formation with concomitant activation of an allylic C-H bond. A variety of functionalized carbon skeletons can be constructed due to the range of enophiles which can be used. For example, carbonyl compounds give homoallylic alcohols and imino derivatives of aldehydes afford homoallylic amines. The azo-ene reaction offers a method for effecting allylic amination by treatment of an alkene with an azo-diester to afford a diacyl hydrazine which upon N-N cleavage furnishes a carbamate. Subsequent hydrolysis of the carbamate provides an allylic amine. Use of chiral diazenedicarboxylates provides a method for effecting stereoselective electrophilic amination. 

Sol 3. (i) In case of carbonyl ene reactions, addition of Lewis acids makes the enophiles more electrophilic, so the reaction can be performed at lower temperature. This also improves the yields, regio- and stereoselectivities of the carbonyl ene reactions. For example, in the Lewis acid—catalyzed carbonyl ene reaction between 2-methylhepta-2,6-diene and oxamalonate, a positive charge develops at the ene component due to which the trisubstimted alkene becomes more reactive than the monosubstituted alkene. 

Addition of an electrophilic carbon species to alkenes is not difficult. The problem is controlling the reactions of the intermediate carbocation which is formed. Our initial approach to this problem was to explore Lewis acid catalyzed ene reactions as a means of controlling the reaction between a weakly nucleophilic alkene and a weakly electrophilic carbon-containing enophile.i During the course of these studies we have found that alkylaluminum halides have several unique properties which make them valuable catalysts for ene reactions and that by proper choice of reaction conditions, other classes of reactions can be induced to occur in synthetically useful yield. 2... 

Only a few reactions belong to the class of group transfer reactions. Most common is the ene reaction, where allyhc hydrogens are transferred to an electrophilic alkene, referred as an enophile. For example,... 

The process of transfer of one hydrogen atom from an allylic alkene (an ene) to an electrophilic alkene (an enophile) followed by formation of a new cr-bond and migration of allylic double bond is known as ene reaction or Alder ene reaction [1]. The ene may be an alkene, alkyne, allene, cyclopropane ring or arene, whereas an enophile may be an alkene, carbonyl, thiocarbonyl, imino or diazo compound having an electron withdrawing substituent. Oxygen may also serve as an enophile. The reaction usually takes place from left to right, since a new [Pg.161]

Many ene reactions can be catalyzed by Lewis acids, particularly aluminum chloride and ethylaluminum chloride. Coordination of aluminum with the carbonyl group of an enophile increases its electrophilicity, making it possible to carry out ene reactions at room temperatures. Entry 4 illustrates this point. 

Ene reactions have relatively high activation energies, and intermolecular reaction is observed only for strongly electrophilic enophiles. Some examples are given in Scheme 6.14. The ene reaction is strongly catalyzed by Lewis acids such as aluminum chloride and diethylaluminum chloride. Coordination by the aluminum at the carbonyl group increases the electrophilicity of the conjugated system and allows reaction to occur below room temperature, as illustrated in entry 6. Intramolecular ene reactions can be carried out under either thermal (entry 5) or catalyzed (entry 6) conditions. ... 

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