Electrophiles electron-rich functionalities

The second chemical principle of interest here is that many biochemical reactions involve interactions between nucleophiles (functional groups rich in electrons and capable of donating them) and electrophiles (electron-deficient functional groups that seek electrons). Nucleophiles combine with, and give up electrons to, electrophiles. Common nucleophiles and electrophiles are listed in Figure 6-21. Note that a carbon atom can act as either a nucleophile or an electrophile, depending on which bonds and functional groups surround it. 

In Chapter 11 we continue our focus on organic molecules with electron-rich functional groups by examining alkynes, compounds that contain a carbon-carbon triple bond. Like alkenes, alkynes are nucleophiles with easily broken n bonds, and as such, they undergo addition reactions with electrophilic reagents. 

Nucleophiles have an electron-rich site, either because they are negatively charged or because they have a functional group containing an atom that has a lone pair of electrons. Electrophiles have an electron-poor site, either because they are positively charged or because they have a functional group containing an atom that is positively polarized. 

As the Br2 molecule gets closer to the alkene, this temporary effect becomes more pronounced. Now we can understand why Br2 functions as an electrophile in this reaction there is a temporary 5+ on the bromine atom that is closer to the pi bond of the alkene. When the electron-rich alkene attacks the electron-poor bromine, we get the following hrst step of our mechanism ... 

They demonstrated that electron-deficient R groups and electron-rich R substituents at S accelerated the reductive elimination. They proposed 123 (Lj = DPPE, R = Ph, R = Ar) as a transition state, where R acts as an electrophile and thiolate as a nucleophile. The Hammet plot for the reductive elimination showed that the resonance effect of the substituent in R determines the inductive effect of the R group, and the effect in SR showed an acceptable linear relationship with the standard o-values. The relative rate for sulfide elimination as a function of the hybrid valence configuration of the carbon center bonded to palladium followed the trend sp > sp spl... 

The facility with which electrophilic halocarbene complexes undergo substitution reactions makes them extremely versatile synthetic intermediates, and this section summarizes these synthetic possibilities. Scheme 3 illustrates the usefulness of RuCl2(=CCl2)(CO)(PPh3)2. When the ligands are bound to electron-rich metal centers the electrophilicity is much reduced and interaction of the M=C function with some electrophiles can be observed. 

Exclusive O/H insertion takes place in the Rh2(OAc)4-catalyzed reaction of diethyl diazomalonate with a,(J-unsaturated y-hydroxyesters 167 a-c163). This is not surprising in view of the reluctance of electrophilic metal carbenes to add to electron-poor double bonds (see Sect. 2.3.2). However, the more electron-rich double bond of p-methoxybenzyl clavulanate 168 also cannot compete with the O—H function for the same carbenoid 164). The steric situation at the trisubstituted double bonds of 167 and 168 may be reason enough to render an attack there highly unfavorable as compared to the easily accessible O—H function, no matter how nucleophilic the double bond is. 

Gold-catalyzed direct C-H functionalizations enable the formation of polyalkylated arenes under mild conditions. In many cases, branched products are obtained. Two mechanisms are thought to operate with electron-rich arenes, an S si2-type mechanism via Au(lll) leads to the linear product. The branched product is obtained via a Friedel-Craft-type alkylation. A silver salt is often added and is believed to generate a more electrophilic Au(m) species. Often regioselectivities are poor and symmetric arenes are employed. Intramolecular variants as well as Michael additions are also known (Equations (72)-(74)).71,71a,71b... 

The benzylic C-H activation has been effectively applied to the enantioselective synthesis of (+)-imperanene (Equation (16)).80 The key step was the Rh2(i -DOSP)4-catalyzed functionalization of the benzylic methyl C-H bond in arene 2. An impressive feature of this transformation was that both the carbenoid and substrate contained very electron-rich aromatic rings, which were compatible with the highly electrophilic carbenoids because they were still sterically protected. 

The utility of the electrode to promote bond formation between functional groups of the same polarity provides researchers with an opportunity to explore the chemistry of interesting intermediates, and synthetic strategies that are based on their intermediacy [1,2], Reduction at a cathode, or oxidation at an anode, renders electron-poor sites rich, and electron-rich sites, poor. For example, the reduction of an a, 8-unsaturated ketone leads to a radical anion in which the -carbon possesses nucleophilic, rather than electrophilic character. Similarly, oxidation of an enol ether affords a radical cation wherein the -carbon displays electrophilic, rather than its usual nucleophilic behavior [3]. 

Tricarbonyliron-coordinated cyclohexadienylium ions 569 were shown to be useful electrophiles for the electrophilic aromatic substitution of functionally diverse electron-rich arylamines 570. This reaction combined with the oxidative cyclization of the arylamine-substituted tricarbonyl(ri -cyclohexadiene)iron complexes 571, leads to a convergent total synthesis of a broad range of carbazole alkaloids. The overall transformation involves consecutive iron-mediated C-C and C-N bond formation followed by aromatization (8,10) (Schemes 5.24 and 5.25). 

The first route relies on the ROP of cyclic ketene acetals [1-3]. The electron-rich double bond is prone to react with radicals and electrophiles. Therefore, this class of monomers undergoes cationic and radical polymerization. For example, radical initiators react with the double bond to provide a new tertiary radical (Fig. 2). Two distinct mechanisms of polymerization can then take place direct vinyl polymerization or indirect ring opening of the cycle accompanied by the formation of a new radical, which is the propagating species (Fig. 2). The ester function is formed... 

In addition to these extensive studies on electrophile-mediated intramolecular peroxydation of electron-rich C=C bonds, some examples of intramolecular hydroperoxide addition to electron-poor C=C bonds have been described. For example, several racemic analogues 371 of the naturally occurring plakinic acid were readily obtained by peroxymercuration followed by hydridodemercuration of the dienic acids 370 (Scheme 95 f °. Intramolecular Michael addition of hydroperoxide function to the double... 

The carbon dioxide molecule exhibits several functionalities through which it may interact with transition metal complexes and/or substrates. The dominant characteristic of C02 is the Lewis acidity of the central carbon atom, and the principle mode of reaction of C02 in its main group chemistry is as an electrophile at the carbon center. Consequently, metal complex formation may be anticipated with basic, electron-rich, low-valent metal centers. An analogous interaction is found in the reaction of the Lewis acid BF3 with the low-valent metal complex IrCl(CO)(PPh3)2 (114). These species form a 1 1 adduct in solution evidence for an Ir-BF3 donor-acceptor bond includes a change in the carbonyl stretching frequency from 1968 to 2067 cm-1. 

Chemical bonds are formed by electrons, and formation or breakage of bonds requires the migration of electrons. In broad terms, reactive chemical groups function either as electrophiles or as nucleophiles. Electrophiles are electron-deficient substances that react with electron-rich substances nucleophiles are electron-rich substances that react with electron-deficient substances. The task of a catalyst often is to make a potentially reactive group more reactive by increasing its electrophilic or nucleophilic character. In many cases the simplest way to do this is to add or remove a proton. 

Electron-rich, unsaturated hydrocarbons, which are normally resistant to nucleophilic attack, become generally reactive towards nucleophiles upon complexation to an electrophilic transition metal such as palladium(II), platinum(II) or iron(II). Complexation also directs the regio- and stereo-chemistry of the nucleophilic attack, the result of which is a new organometallic complex, which can often be used to promote additional functionalization of the original substrate. Synthetically useful examples of such processes are presented in the following sections. 

The functionalization of electron rich aromatics rings is often accomplished by electrophilic aromatic substitution. However, electrophilic substitutions require stringent conditions or fail entirely with electron deficient aromatic rings. Nucleophilic aromatic substitutions are commonly used but must usually be conducted under aprotic conditions. In contrast, nucleophilic radicals can add to electron deficient aromatic rings under very mild conditions. 

Decamethylsilicocene (82) can be regarded as an electron-rich silicon(II) compound containing a hypercoordinated silicon atom. The chemistry of 82 is determined by (a) the nucleophilicity of the silicon lone-pair (cr-donor function towards electrophiles, oxidative-addition processes) and (b) the weakness of the silicon-(cyclopentadienyl)carbon jr-bond rearrangement, Si—C bond cleavage). In the following section, the chem-... 

Irreversible inhibitors act by covalently modifying the enzyme, generally at the active site. The active site is then blocked, and the enzyme is permanently rendered inactive. Because functional groups in the active site tend to be electron rich and nucleophilic, irreversible inhibitors tend to be electrophiles. Acylation agents are especially common. 

Iodine, NIS, PhSeCl, and AUCI3 have been shown to trigger the electrophilic 6(O) "-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones (22) to produce highly substituted furans (23) (Scheme 3). Various nucleophiles, including functionally substituted alcohols, H2O, carboxylic acids, 1,3-diketones, and electron-rich arenes, and a range of cyclic and acyclic 2-(alk-l-ynyl)alk-2-en-l-ones readily participate in these cyclizations.40... 

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