Nucleophiles Electrophilic addition

Nuc E), forming a dipole for cycloaddition, to produce (Scheme 2 (3)) a cyclic imino species. The latter general type of reaction (Scheme 1 (2)), involving the addition of an electrophile (E) to the ligated nitrile, yields (Scheme 2 (4)) azavinylidene products, [M]-N=C(E)R. Sequential nucleophilic-electrophilic additions have also been performed (Scheme 3), leading to a stepwise and alternative mode of ligand activation. 

Generally, the chemistry from the PET reactions is governed by the chemical properties and the reactivity profiles of the ion radicals formed. The most common pathways available to these reactive intermediates is the uni-molecular dissociation to ions and radicals besides isomerization, cyclodimerization, nucleophilic/electrophilic addition, and substitution reactions. 

The sequential nucleophile/electrophile addition can also be applied to the dearomatization of naphthalene and derivatives. Treatment of [Cr(CO)3(l,4-dimethoxynaphthalene)] with 2-methyl-2-litihiodithiane affords a single regio-isomeric dihydronaphthalene (Scheme 24) [35, 40]. In the second example in Scheme 26, an a-nitrile anion is used. HMPA is essential in this case to favor alkylation of the metal as opposed to anion dissociation [40]. 

The simplest case corresponds to the one-electron transfer between the electrode and species that are chemically stable on the time scale of the experiments (Eq. (1.1)). However, electrochemical systems are frequently more complicated and the electroactive species take part in successive electron transfer reactions at the electrode (multistep processes) and/or in parallel chemical reactions in solution such as protonation, dimerisation, rearrangement, electron exchange, nucleophilic/electrophilic addition, disproportionation, etc., the product(s) of which may or may not be electroactive in the potential region under study. The simulation of these cases is described in Chapters 5 and 6. 

Initial mechanistic analysis of the Strecker reaction catalyzed by a urea-based organocatalyst (Scheme 3.18) revealed that the catalytic activity is provided by the urea functionality of structurally complex catalyst 1. However, further studies revealed a bifunchonal character of urea and thiourea-based catalysts " as well as the possibility of multiple mechanistic pathways in catalysis of nucleophile-electrophile addition reactions. " Simplified but sufficiently effective (thio)urea catalysts 4a and 4b were used in the hydrocyanation reaction (Scheme 3.19) that was subjected to a combined experimental and computational study. °... 

We can extend the general principles of electrophilic addition to acid catalyzed hydration In the first step of the mechanism shown m Figure 6 9 proton transfer to 2 methylpropene forms tert butyl cation This is followed m step 2 by reaction of the car bocation with a molecule of water acting as a nucleophile The aUcyloxomum ion formed m this step is simply the conjugate acid of tert butyl alcohol Deprotonation of the alkyl oxonium ion m step 3 yields the alcohol and regenerates the acid catalyst... 

When formulating a mechanism for the reaction of alkynes with hydrogen halides we could propose a process analogous to that of electrophilic addition to alkenes m which the first step is formation of a carbocation and is rate determining The second step according to such a mechanism would be nucleophilic capture of the carbocation by a halide ion... 

Initiation is an electrophilic addition of a cation across the double bond, but because of the poor nucleophilicity of the initiator s counterion. 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

Next, examine the highest-occupied and lowest-unoccupied molecular orbitals (HOMO and LUMO) of dichlorocarbene. Were the reaction a nucleophilic addition , how would you expect CCI2 to approach propene Were the reaction an electrophilic addition , how would you expect CCI2 to approach propene Which inteqDretation is more consistent with the geometry of the transition state ... 

The electrophilic addition of HBr to ethylene is only one example of a polar process there are many others that vve ll study in detail in later chapters. But regardless of the details of individual reactions, all polar reactions take place between an electron-poor site and an electron-rich site and involve the donation of an electron pair from a nucleophile to an electrophile. 

Before beginning a detailed discussion of alkene reactions, let s review briefly some conclusions from the previous chapter. We said in Section 5.5 that alkenes behave as nucleophiles (Lewis bases) in polar reactions. The carbon-carbon double bond is electron-rich and can donate a pair of electrons to an electrophile (Lewis acid), for example, reaction of 2-methylpropene with HBr yields 2-bromo-2-methylpropane. A careful study of this and similar reactions by Christopher Ingold and others in the 1930s led to the generally accepted mechanism shown in Figure 6.7 for electrophilic addition reactions. 

Aikene chemistry is dominated by electrophilic addition reactions. When HX reacts with an unsymmetrically substituted aikene, Markovnikov s rule predicts that the H will add to the carbon having fewer alky) substituents and the X group will add to the carbon having more alkyl substituents. Electrophilic additions to alkenes take place through carbocation intermediates formed by reaction of the nucleophilic aikene tt bond with electrophilic H+. Carbocation stability follows the order... 

The same high reactivity of radicals that makes possible the alkene polymerization we saw in the previous section also makes it difficult to carry out controlled radical reactions on complex molecules. As a result, there are severe limitations on the usefulness of radical addition reactions in the laboratory. Tn contrast to an electrophilic addition, where reaction occurs once and the reactive cation intermediate is rapidly quenched in the presence of a nucleophile, the reactive intermediate in a radical reaction is not usually quenched, so it reacts again and again in a largely uncontrollable wav. 

HC1, HBr, and HI add to alkenes by a two-step electrophilic addition mechanism. Initial reaction of the nucleophilic double bond with H+ gives a carbo-cation intermediate, which then reacts with halide ion. Bromine and chlorine add to alkenes via three-membered-ring bromonium ion or chloronium ion intermediates to give addition products having anti stereochemistry. If water is present during the halogen addition reaction, a halohydrin is formed. 

Another method for the synthesis of epoxides is through the use of halo-hydrins, prepared by electrophilic addition of HO—X to alkenes (Section 7.3). When halohydrins are treated with base, HX is eliminated and an epoxide is produced by an intramolecular Williamson ether synthesis. That is, the nucleophilic alkoxide ion and the electrophilic alkyl halide are in the same molecule. 

Many mechanistic results on this electrophilic addition are available but most of them deal with the first steps of the reaction in which the ionic intermediate is formed, rather than with the last steps in which the products are obtained by nucleophilic attack on this intermediate (ref. 2). The present paper reports results on the selectivity of olefin bromination, which have been obtained more or less systematically with a view to improving the existing rules which are too naive to be useful in synthesis (ref. 3). 

This intermediate is similar to those encountered in the neighboring-group mechanism of nucleophilic substitution (see p. 404). The attack of W on an intermediate like 2 is an Sn2 step. Whether the intermediate is 1 or 2, the mechanism is called AdE2 (electrophilic addition, bimolecular). 

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. 

Alkyl substituents accelerate electrophilic addition reactions of alkenes and retard nucleophilic additions to carbonyl compounds. The bonding orbital of the alkyl groups interacts with the n bonding orbital, i.e., the HOMO of alkenes and raises the energy (Scheme 22). The reactivity increases toward electron acceptors. The orbital interacts with jt (LUMO) of carbonyl compounds and raises the energy (Scheme 23). The reactivity decreases toward electron donors. 

Therefore, the preference of the cycloadditions is opposite in direction to the biases observed in nucleophilic additions of 2-substituted 9,10-dihydro-9,10-ethanoanthracen-11-ones (34) (dibenzobicyclo[2.2.2]octadienones) and in electrophilic additions of 2-substituted 9,10-dihydro-9,10-ethenoanthracenes (dibenzobicyclo[2.2.2]octatrienes) 71 [103]. 

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

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