Nucleophilic addition to double bonds

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

In general, the mechanisms of nucleophilic additions to double bonds have not been as much studied or systemized as those of electrophilic addition. Reactions 7.51 and 7.52 are examples of the very useful Michael condensation, in which a carbanion adds to an a,/ -unsaturated carbonyl or nitrile compound. The usefulness of these reactions arises from the fact that the number of ways of building longer carbon chains from smaller ones is limited. 

B. Nucleophilic Addition to Double Bonds. There are at least two reports of 0 adding in nucleophilic fashion to a carbon-carbon double bond. Although the reaction mechanisms were not elucidated in detail, in both reports the double bond was activated for nucleophilic addition. 

Other limitations of the reaction are related to the regioselectivity of the aryl radical addition to double bond, which is mainly determined by steric and radical delocalization effects. Thus, methyl vinyl ketone gives the best results, and lower yields are observed when bulky substituents are present in the e-position of the alkene. However, the method represents complete positional selectivity because only the g-adduct radicals give reductive arylation products whereas the a-adduct radicals add to diazonium salts, because of the different nucleophilic character of the alkyl radical adduct. ... 

In the case of methyl radical addition to double bonds, L. Herk, A. Stefani, and M. Szwarc [J. Am. Chem. Soc., 83, 3008 (1961)] have drawn attention to the importance of the electron-withdrawing power of the conjugated substituent in determining the reactivity of olefins. More recently, to explain a somewhat similar phenomenon, F. Minisci and R. Galli (Tetrahedron Letters, 1962, 533) have invoked the concept that CHS is nucleophilic in character. 

Next to nucleophilic displacement, the commonest mechanistic processes in enzymatic catalysis are addition to double bonds and elimination to form double bonds. These often involve addition of a nucleophile together with a proton to a highly polarized double bond such as C=O or C=N-. In other reactions, which are discussed in Section C,2, the nucleophile attacks one end of a C=C bond that is polarized by conjugation with C=0 or C=N. 

Electrophilic addition to double bonds gives three-membered ring intermediates with Br2, with Hg2+, and with peroxy-acids (in which case the three-membered rings are stable and are called epoxides). All three classes of three-membered rings react with nucleophiles to give 1,2-difunctionalized products with control over (1) regioselectivity and (2) stereoselectivity. Protonation of a double bond gives a cation, which also traps nucleophiles, and this reaction can be used to make alkyl halides. Some of the sorts of compounds you can make by the methods of this chapter are shown below. 

The reactions in this section cover the conjugate (Michael) addition of various lithiated nucleophiles to activated olefins such as enones and enoates. Lithium enolates are formed as intermediates during the addition process. They can be treated as such and trapped, for instance, by an electrophile to provide ketones or esters substituted both in the a and positions. We will focus only on the most important information relevant to the intermediate enolates, and those are rarely discussed in the literature on the Michael addition. The reader can advantageously consult Chapter 14 of the first part of this volume133, which is entirely dedicated to the organolithium additions to double bonds, for a more extensive coverage of the topic. 

Because the elementary reactions of cationic alkene polymerizations are directly related to the organic chemistry of carbocations, Chapter 2 will investigate electrophilic additions to double bonds, nucleophilic substitution, electrophilic aromatic substitution, and elimination reactions. 

Additions to nonactivated olefins and dienes are important reactions in organic synthesis [1]. Although cycloadditions may be used for additions to double bonds, the most common way to achieve such reactions is to activate the olefins with an electrophilic reagent. Electrophilic activation of the olefin or diene followed by a nucleophilic attack at one of the sp carbon atoms leads to a 1,2- or 1,4-addition. More recently, transition metals have been employed for the electrophilic activation of the double bond [2]. In particular, palladium(II) salts are known to activate carbon-carbon double bonds toward nucleophilic attack [3] and this is the basis for the Wacker process for industrial oxidation of ethylene to acetaldehyde [41. In this process, the key step is the nucleophilic attack by water on a (jt-ethylene)palladium complex. 

Carbocations, however formed, are very electrophilic. They react readily with nucleophiles, as shown in reaction (5.18). These reactions are important as steps in electrophilic addition to double bonds and unimolecular nucleophilic substitution (SnI) reactions. 

Why do the adduct carbocations 46 not react with a nucleophile to give an adduct of type 48, as happens in electrophilic addition to double bonds The main reason is probably thermodynamic. The hypothetical reaction (5.32) is very exothermic, based on experimental heats of formation. If we attribute this exothermicity to the stabilization of the benzene nucleus, we obtain a value of 150 kJ mol-1 for this stabilization. This stabilization would be lost in reaction (5.31) if the adduct 48 were formed, but is regained if the substituted product 47 is produced. This stabilization does not apply to reaction with alkenes, so addition can take place if the reaction is favourable energetically. 

Besides addition to double bonds to give dihalocyclopropane derivatives—the most important reaction of dihalocarbenes—many other reactions of these active electrophilic species can be performed using PTC methodology, such as insertion into C-H bond, reactions with primary and secondary amines and with many other nucleophiles ... 

We have seen several examples of reactions in which two reactants give not a single product but mixtures. Examples include halogenation of alkanes (eq. 2.13), addition to double bonds (eq. 3.31), and electrophilic aromatic substitutions (Sec. 4.11), where more than one isomer may be formed from the same two reactants. Even in nucleophilic substitution, more than one substitution product may form. For example, hydrolysis of a single alkyl bromide gives a mixture of two alcohols in eq. 6.14. But sometimes we find two entirely different reaction types occurring at the same time between the same two reactants, to give two (or more) entirely different types of products. Let us consider one example. 

In the nucleophilic addition, the double bond of alkene is in the limiting step attacked by the nucleophilic component Y of the reactant XY being added, rather than by the electrophilic component X, as in Eq. (6.1). For this mechanism to be sufficiently effective, Y must possess a high-lying bonding MO that can provide adequate overlap with the 7c -MO of the double bond. The free anions Y satisfy this condition best. The addition of Y to the double bond of alkene is usually the rate-determining stage of the addition-elimination (AdE) mechanism of substitution reactions at the sp -carbon atom [21, 22] ... 

Primary alcohols react by an Sj 2 mechanism in which water is displaced by the nucleophilic halide ion because the primary carbon atom is sterically accessible to the nucleophile. The alternate mechanism would have a high activation energy because the transition state would resemble a highly unstable primary carbocation. We used a similar argument to explain the direction of electrophilic addition to double bonds. According to the Hammond postulate, the structure of a transition state resembles the species that is most similar to it in energy. In the case of the mechanism for the reaction of an al-... 

Ordinarily nucleophilic addition to the carbon-carbon double bond of an alkene is very rare It occurs with a p unsaturated carbonyl compounds because the carbanion that results IS an enolate which is more stable than a simple alkyl anion... 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

Such an intermediate ean also stabilize itself by combining with a positive species. When it does, the reaction is nucleophilic addition to a C=C double bond (see Chapter 15). It is not surprising that with vinylie substrates addition and substitution often compete. For chloroquinones, where the charge is spread by resonance, tetrahedral intermediates have been isolated ... 

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