Addition reactions of other electrophilic reagents

CHAPTER 4 ELECTROPHILIC ADDITIONS TO CARBON-CARBON MULTIPLE BONDS 

SECTION 4.7. ELECTROPHILIC SUBSTITUTION ALPHA TO CARBONYL GROUPS 

Although the reaction of ketones and other carbonyl compounds with electrophiles such as bromine is formally a substitution process, it is mechanistically closely related to electrophilic additions to alkenes. The enol or enolate derived from the carbonyl compound is the reactive species, and the initial attack is similar to the electrophilic attack on alkenes. The reaction is completed by restoration of the carbonyl bond, rather than by addition of a nucleophile. The acid- and base-catalyzed halogenation of ketones, which were discussed briefly in Part A, Chapter 7, are the best-studied examples of the reaction. The most common preparative 

Since the reactions involving bromine or chlorine evolve hydrogen halide, they are autocatalytic. In reactions with iV-bromosuccinimide or tetrabromocyclo-hexadienone no hydrogen bromide is formed, so this method may be preferable in the case of acid-sensitive compounds. 

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Scheme 4.2. Addition Reactions of Other Electrophilic Reagents...

It can be observed that in several cases the addition reaction proceeds with excellent diastereomeric excesses. Although the reaction temperature, the solvent and the nature of the counter anion are different from case to case, nevertheless the data reported in the table can be used to have preliminary indications about the ability of the various electrophilic reagents to transfer the chirality to the newly generated stereocenters. The information gained from these experiments, however, must be used with caution since the stereoselectivity is also a function of the alkene employed and examples are known in which a reagent which gives unsatisfactory results with styrene can, in contrast, be efficient with other alkenes. This is clearly evident from the data reported in Table 2 in which the diastereomeric excesses measured for the reactions of the electrophilic reagents derived from the diselenides 24 and 26 with various alkenes are reported. In both cases the results obtained with other alkenes are much better than those observed with styrene. 

The addition of protons is certainly the most common nucleophilic reaction of reduced hydrocarbon species due to the almost ubiquitous availability of proton donors, which may or not be wanted. However, under strictly aprotic conditions it is also possible to add other electrophilic reagents such as alkyl halides, acyl halides, CO2, and SO2. 

In principle, pyrylium salts can be transformed to pyrans by the addiiion of an appropriate reagent to the 2-, 4-, or 6-position of the heterocycle. Although most transformations seem to be nucleophilic additions (because of the electrophilic character of the pyrylium substrates) some reactions, such as hydrogenation or one-electron reductions, are of a radical nature. Many nucleophilic additions to pyrylium salts proceeding via unstable pyran intermediates seem to be of general synthetic interest, especially in the fields of aromatic and other conjugated systems, l97 200 but are of little interest in pyran chemistry. 

This is true for the addition of hydrogen halide (H-X), halogens (X-X) and other electrophilic reagents (NO —Cl, I — Nj, etc.) to cyclohexenes. The oxymercuration reaction (Hg(OAc>2) in the presence of several nucleophiles (H20, AcOH, ROH) is another well known example. 

Reactions of Enamines with Other Electrophilic Reagents Addition of aldehydes to enamines, followed by hydrolysis, leads to monoalkylidene and monoarylidene ketones (81).272 An example in which this reaction occurs intramolecularly is provided by the alkaloid ajmaline.273... 

Direct metallation of methylenecyclopropane with butyllithium in THF affords meth-ylenecyclopropyllithium. This reacts with carbonyl electrophiles such as aldehydes, ketones and lactones by ring alkylation to give selectively 2-methylenecyclopropyl carbinols. No products of exo alkylation are isolated. Other bases such as r-BuOK and KH do not deprotonate methylenecyclopropane. Use of diethyl ether as the solvent, instead of THF, significantly reduced the rate of lithiation. Similar reaction of the lithium reagent with ethylene oxide gave 2-(2-methylenecyclopropyl)ethanol (equation 294) In the reaction with C-labeled ethylene oxide the addition of TMEDA to the reaction mixture is recommended. ... 

An additional important result follows from rule (a). It seems that in polar cycloaddition reactions the most electrophilic reagent control the asynchronicity of the process by a larger bond formation process at the most electrophilic site of the electron acceptor. This result may be traced to the more prevalent role of the electron acceptor in the electrophile/nucleophile interaction, which follows from the extra work associated with the redistribution of the electronic charge that it takes from the nucleophilic partner. The local electrophilicity counterpart, on the other hand, consistently predicts the regiose-lectivity expected in DA and 1,3-dipolar cycloadditions. 

The formation of the bridged intermediate has been represented as an SN2-like displacement of the leaving group from the sulfenyl sulphur of 85 , or alternatively, as reported in equation 90 in agreement with the addition of other electrophiles to alkenes, it has been proposed that the reaction involves the initial formation of 7r-complex 86 in a rapid equilibrium with the reagents . 

The electrophilic addition reactions of A -unsaturated steroids and other rigid cyclohexenes are controlled mainly by the conformational preference for diaxia) addition HOBr, for example, gives mainly a 5a-bromo-6)5-alcohol. A study of similar reactions with B-nor-A -unsaturated steroids suggests that the reaction of a cyclopentene is under electronic rather than conformational control.A variety of reagents (HOBr, BrF, Brj, BrOMe, and BrOAc) gave mainly 6a-bromo-5)S-substituted derivatives (155), indicating that the initial product, a 5a.6a-bromonium ion (154). reacts further according to Markovnikoff, with attack of the anion at the tertiary 5 -position. 

We have already studied one addition reaction of alkenes—hydrogenation—in which a hydrogen atom is added at each end of a double (or triple) bond. In this chapter we shall study other alkene addition reactions that do not involve the same mechanism as hydrogenation. We can depict this type of reaction generally, using E for an electrophilic portion of a reagent and Nu for a nucleophilic portion, as follows. 

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