Electrophilic activation involving

Zhang, Y. Aguirre, S. A. Klumpp, D. A. Reactive, Dicationic Electrophiles Electrophilic Activation Involving the Phosphonium Group. Tetrahedron Lett. 2002, 43, 6837-6840. 

Halonium ions are an important class of onium ions.43 The dialkylchloro, bromo, and iodohalonium ions can be prepared and even isolated as stable salts (i.e., 46), as shown by Olah et al. by reacting an excess of haloalkane with strong Lewis acid halides in solvents of low nucleophilic-ity (eq 14). In superacid solution, dialkylhalonium ions show enhanced alkylating reactivity.44 It is considered that this enhanced reactivity is due to further protolytic (or electrophilic) activation involving the non-bonded... 

The same pathway of activation has been postulated in the formation of quinones, although the putative 6-hydroxyBP precursor has never been isolated (19,20). In this mechanism, formation of quinones would proceed by autoxidation of 6-hydroxyBP (20). However, substantial evidence indicates that the first step in formation of quinones does not involve the typical attack of the electrophilic active oxygen to yield 6-hydroxyBP, but instead consists of the loss of one electron from BP to produce the radical cation. 

In summary, transifion-metal-catalyzed alkene-polymerization reactions highlight the metal-induced electrophilic activation of C—C n bonds to form carbo-cation-like alkene complexes. Considerations involving substituent pi-donor or pi-acceptor strength (i.e., tendency toward carbocation formation) will be useful in similarly rationalizing polymerization reactions (4.105) for more general alkenes. 

Homogeneous catalysts have been reported, which can oxidize methane to other functionalized products via C-H activation, involving an electrophilic substitution process. The conversion of methane into methyl bisulfate, using a platinum catalyst, in sulfuric acid, has been described. The researchers found that a bipyrimidine-based ligand could both stabilize and solubilize the cationic platinum species under the strong acidic conditions and TONs of >500 were observed (Equation (5)).13... 

The skeletal rearrangements are cycloisomerization processes which involve carbon-carbon bond cleavage. These reactions have witnessed a tremendous development in the last decade, and this chemistry has been recently reviewed.283 This section will be devoted to 7T-Lewis acid-catalyzed processes and will not deal, for instance, with genuine enyne metathesis processes involving carbene complex-catalyzed processes pioneered by Katz284 and intensely used nowadays with Ru-based catalysts.285 By the catalysis of 7r-Lewis acids, all these reactions generally start with a metal-promoted electrophilic activation of the alkyne moiety, a process well known for organoplatinum... 

The authors point out that the dependence of the site of electrophilic attack on the ligand trans to the hydride in the model systems may be important with respect to alkane activation. If the information is transferable to Pt-alkyls, protonation at the metal rather than the alkyl should be favored with weak (and hard ) a-donor ligands like Cl- and H20. These are the ligands involved in Shilov chemistry and so by the principle of microscopic reversibility, C-H oxidative addition may be favored over electrophilic activation for these related complexes. 

In 1978, Negishi et al. reported highly regio- and stereoselective methylalumination of alkynes with Me3Al using a zirconocene catalyst [59]. The involvement of cationic zirconocene species in the activation of carbon—carbon triple bonds was suggested in a reaction mechanism featuring electrophilic activation by aluminum (Scheme 8.30). 

Much of our research has involved the use of dicationic electrophiles in reactions with very weak nucleophiles, such as non-activated arenes and alkanes. By comparison to similar monocationic electrophiles, we have been able to show the extent of electrophilic activation by adjacent cationic centers. For example, carbocations show an increased reactivity with a nearby cationic charge (eqs 3-4).9 When 1,1-diphenyletheneis reacted with superacidic CF3SO3H... 

An alternative to the above is esterification by reaction of the salt of the Fmoc-amino acid with the halomethylphenyl-support (see Section 3.17). It was established in the 1960s that this method of esterifying A-alkoxycarbonylamino acids, which does not involve electrophilic activation, is not accompanied by enan-tiomerization. Examples of supports with haloalkyl linkers are bromomethylphe-noxymethyl-polystyrene and 2-chlorotrityl chloride resin (see Section 5.23). 

In aromatic systems, the Lewis acids which activate via coordination are also capable of activating the aromatic system by the formation of a and ir complexes. There are a sufficient number of examples available to indicate that the activation via the latter processes is the more important of these, where all are present. Olivier (52) showed in 1913 that the kinetic behavior of such reactions consists of two portions. When the catalyst, say aluminum chloride, is present in less than the amount required to complex all the functional groups, the reaction is relatively slow and the catalytic activity is due to the small amount of Lewis acid resulting from the dissociation of the complex. As soon as all the functional groups are coordinated, any additional Lewis acid is found to accelerate the rate enormously. In these electrophilic substitutions it seems highly probable that the the activation involves the pi electron system of the benzene ring. Olivier studied the reaction sequence ... 

Ames Test The Ames test, developed by Bruce Ames and his coworkers at the University of California, Berkeley, depends on the ability of mutagenic chemicals to bring about reverse mutations in Salmonella typhimurium strains that have defects in the histidine biosynthesis pathway. These strains will not grow in the absence of histidine but can be caused to mutate back to the wild type, which can synthesize histidine and hence can grow in its absence. The postmitochondrial supernatant (S-9 fraction), obtained from homogenates of livers of rats previously treated with PCBs in order to induce certain cytochrome P450 isoforms, is also included in order to provide the activating enzymes involved in the production of the potent electrophiles often involved in the toxicity of chemicals to animals. 

Although electrophilic reactions involving dications with deactivated arenes may suggest the formation of superelectrophilic intermediates, there are a number of well-known examples of monocationic electrophiles that are capable of reacting with benzene or with deactivated aromatic compounds. For example, 2,2,2-trifluoroacetophenone condenses with benzene in triflic acid (eq 12).13 A similar activation is likely involved in the H2SO4 catalyzed reaction of chloral (or its hydrate) with chlorobenzene giving DDT (eq 13). 

Thus, many metal ions catalyze the hydrolysis of esters [7,8], amides [9], and nitriles [10] via electrophilic activation of the C=0 or C=N group. This type of catalysis is characteristic of coordination complexes and is very common in metalloenzyme-mediated processes. Zinc(II), for example, is a key structural component of more than 300 enzymes, in which its primary function is to act as a Lewis acid (see Chapter 4). The mechanism of action of zinc proteases, e.g., thermolysin, involves electrophilic activation of an amide carbonyl group by coordination to zinc(II) in the active site (Figure 4). 

The accepted reaction mechanism for the electrophilic aromatic nitration was postulated by Ingold in 1969[3] and involves several steps (Scheme 5.1). Firstly, the nitric acid is protonated by a stronger acid (sulfuric). The protonated nitric acid gives water and the nitronium ion (N02+) which is the electrophilic active species for nitration of aromatics. Nitric acid heterolysis is considered to be accelerated by the polarity of the solvent, and solvation of nitronium ion in different media affects its reactivity and the selectivity of the reaction. Combination of nitronium ion and an aromatic molecule form an intermediate named the Wheland complex or er-complex. The loss of a proton from the er-complex gives the aromatic nitrocompound (Scheme 5.1). 

Roha et ah 367) claim that the addition of a strong electrophile, such as AlClg, to a Ziegler catalyst produces a more active, homogeneous Ti+4 catalyst for ethylene polymerization. They proposed that electrophilicity is involved in the formation of the alkyl metal-transition metal complex and in complexity and orienting monomer. 

On the other hand, our own group and Jochims and coworkers in Germany found recently and independently another pathway for formation of the A -acyliminium ions from aldehydes and nitriles in which the order of activation of the reagents differs from that in the Ritter reaction. The method involves an initial electrophilic activation of the... 

Recently, a new effective method for electrophilic activation of carbonyl compounds was proposed in order to enable the latter to react with weak nucleophiles such as nitriles102. This method involves the conversion of aldehydes and ketones into highly active acyloxycarbenium ions 163. This new type of carboxonium ions is related to the hydroxycarbenium and alkoxycarbenium ions 105, whose high stability is well known76. 

Pd-catalyzed cycloisomerization of (Z)-2-en-4-yne-l-thiols 111 gives substituted thiophenes 112. The mechanism involves electrophilic activation of the alkyne moiety by Pd(ll) followed by intramolecular cyclization, protonolysis, and aromatization (Scheme 25) <20000L351>. S-Endo cyclization of alkynyl thiols 113 using a Mo, W, or Cr catalyst affords dihydrothiophene 114 <2000S970>. 

On the other hand, however, these two areas of cationic polymerization are not completely separated fields. In spite of the differences, both processes proceed on electron-deficient active species cations or species with a partial positive charge. Thus, propagation in both cases involves attack of the nucleophile (double bond or heteroatom) on electrophilic active centers. Several basic principles will therefore hold for both vinyl and ring-opening cationic polymerization. 

The key to successfiilly using dimethyl sulfoxide as an oxidant for alcohols is to activate the sulfur atom prior to reaction with a nucleophilic alcohol function. This activation involves electrophilic attack upon the sulfinyl oxygen by a varied of electrophiles. The initial product formed when an alcohol does attack the activated dimethyl sulfoxi is known to be the sulfcmium salt (1 Scheme 1). 

Two overall mechanisms have been considered for snch reactions one (Scheme 3) occurs via an electrophilically activated oxo-donor (XO) toward the oxo-acceptor (Y), npon coordination to a Lewis acid ReO center and the other one (Scheme 4) involves a metal-centered oxygen transfer via a Re 0 / Re 02 couple that parallels that of Mo oxotransferases (via the isoelectronic Mo /Mo couple). 

Many methods of ruthenium-promoted C-C bond formation implicating alkynes have been discovered. Most of these have involved oxidative coupling at a ruthe-nium(O) or (II) site, rather than addition of carbonucleophiles to electrophilically activated alkynes. These methods have been reported in several reviews [3,122]. 

---