Enolate anions, arylation mechanism

Mechanistic information from these reactions points to the initial formation of a radical anion of the aromatic compound, followed by loss of halide ion (3.15) subsequent attack by a second enolate anion and electron transfer to a second molecule of aryl halide provides the substitution product, and the reaction is propagated. The operation of a chain mechanism is indicated by the observation that quantum... 

The enolate anions of 2-acetylthiophene and 2-acetylfuran have been arylated under photochemical conditions in the presence of t-BuOK and good electron donors such as acetone enolate (entrainment reaction) to give the corresponding benzyl 2-thienyl and 2-furanyl ketones respectively. Use of FeBr2 as initiator in a dark reaction gives good yields of the substitution products without the need for added nucleophiles, and it is suggested that these arylation processes occur by an SrnI mechanism. 

The procedure reported here is based on a reaction discovered by Bunnett and Creary, and was first employed for preparative purposes by Bunnett and Traber.3 It is attractive because of the high yield obtained, the ease of work-up, and the cleanliness of the reaction. The reaction is believed to occur by the SRN1 mechanism, which involves radical and radical anion intermediates.2,4 The SRN1 arylation of other nucleophiles, especially ketone enolate ions,5 ester enolate ions,6 picolyl anions,7 and arenethiolate ions,8 has potential application in synthesis. 

An Sj l mechanism has been implicated in the photochemical reaction of diarylsulphides (and the corresponding sulphoxides and sulphones) with the enolate of pinacolone, and with diphenylphosphide anion and diethylphosphite anion.The products are derived from reaction of the anions with aryl radicals formed by cleavage of an aryl sulphur bond in a diarylsulphide radical anion intermediate. Thus (146) is formed from diphenylsulphide and the enolate of pinacolone. 

There is good evidence that some nucleophilic substitution reactions do involve a single electron transfer, but the best established use a slightly different mechanism. These are the SrnI reactions, with the subscript RN standing for radical nucleophilic. Examples are the reaction of the nitronate anion 4.14 with p-nitrobenzyl chloride 4.15, 251 and the reaction of the pinacolone enolate 4.16 with bromobenzene.252 The former might have been a straightforward SN2 reaction, but actually takes the S l pathway because the nitro groups make the electron transfer exceptionally easy. The latter cannot take place by a conventional Sn2 reaction, because aryl (and vinyl) halides are not susceptible to direct displacement, and the S l pathway overcomes this difficulty. 

Another reaction that cannot be an SN2, because of the impossibility of carrying it out on an aryl halide, is the displacement from the aryl bromide 7.187. The mechanism is an Sr jI reaction (see p. 147), involving an electron transfer from the enolate 7.186 to the halide 7.187. The radical anion 7.189 loses the bromide ion to give the aryl radical 7.190, and this couples with the radical 7.188 derived from the nucleophile to give the ketone 7.191.252 The m-mcthyl group shows that the reaction did not take place by way of a benzyne. 

The preceding reactions dealt with the use of chiral auxiliaries linked to the electrophilic arene partner. The entering nucleophile can also serve as a chiral controller in diastereoselective SjjAr reactions. This approach was successfully employed for the arylation of enolates derived from amino acids. To illustrate the potential of the method, two examples have been selected. Arylation of Schollkopf s bislactim ether 75 with aryne 77 as electrophilic arylation reagent was demonstrated by Barrett to provide substitution product 81 with good yield (Scheme 8.18) [62, 63]. Aryne 77 arises from the orf/jo-lithiation of 76 between the methoxy and the chlorine atom followed by elimination of LiCl. Nucleophilic attack of 77 by the lithiated species 78 occurs by the opposite face to that carrying the i-Pr substituent. Inter- or intramolecnlar proton transfer at the a-face of the newly formed carbanion 79 affords the anionic species 80. Subsequent diastereoselective reprotonation with the bulky weak acid 2,6-di-f-butyl-4-methyl-phenol (BHT) at the less hindered face provides the syn product 81. Hydrolysis and N-Boc protection give the unnatural arylated amino acid 82. The proposed mechanism is supported by a deuterium-labeling experiment. Unnatural arylated amino acids have found application as intermediates for the construction of pharmaceutically important products such as peptidomi-metics, enzyme inhibitors, etc. [64, 65]. 

This paper describes two new classes of organo-carbonate compounds which are designed to contain a choline or choline mimic to provide high affinity at the anionic site, and a latent electrophilic group that can be released by reaction at the esteratic site and then react with the serine hydroxyl or a proximal nucleophile. These two general types of inhibitors, aryl carbonates and enol carbonates, are illustrated in Figure 2. The proposed mechanism of inhibition of the aryl carbonate class of inhibitors, similar to that for the enol carbonates, is shown in Figure 3. 

Enolates of NN-disubstituted amides react with halobenzenes on photolysis in liquid ammonia to give a-aryl derivatives, e.g. (213) from iV-methyl-iV-phenylacetamide and chlorobenzene, often in good yields, although the a,a-diphenyl amide is often a contaminant. Most likely, an SrnI mechanism is involved perhaps many more useful reactions will come to light by studying the photochemistry of anions. 

The synthesis of a series of Cu(I) enolate complexes supported by 1,10-phenanthroline has been reported. Their structures consist of an unusual combination of one cationic Cu(I) centre ligated by two 1,10-phenanthroline ligands and one free anionic enolate unit. The reactivity of these complexes and the mechanism of a-arylation reactions through a Cu(in) enolate intermediate have been described. 

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