Carbanions benzyne

It has been found that aryl groups can also be introduced into the a-position of sulphoxides. Corey and Chaykovsky have demonstrated that chlorobenzene reacts at room temperature with an excess of sodium methylsulphinyl carbanion to give methyl benzyl sulphoxide in 41% yield. The authors believe that a benzyne intermediate may be involved in the reaction400,401 (equation 174). 

The stereochemistry of dienes has been found to have a pronounced effect in the concerted cyclo-additions with benzyne 64>65h A concerted disrotatory cyclo-addition of tetrafluorobenzyne, leading for example with trans- (3-methylstyrene to (63, R = Me), is likely and in accord with the conservation of orbital symmetry 68>. However while the electro-cyclic rearrangement of (63, R = H) to (65, R = H) is not allowed, base catalysed prototropic rearrangement is possible. A carbanion (64, R = H) cannot have more than a transient existence in the reaction of tetrafluorobenzyne with styrene because no deuterium incorporation in (65) was detected when either the reaction mixture was quenched with deuterium oxide or when the reaction was conducted in the presence of a ten molar excess of deuteriopentafluorobenzene. 

The Dow Process utilizes an elimination/addition reaction to convert chlorobenzene to phenol. The proposed mechanism for this reaction is shown in Figure 8-3. The high-temperature reaction begins with chlorobenzene and aqueous sodium hydroxide. Note that this mechanism starts with the hydroxide attacking as a base, beginning dehydrohalogenation to form benzyne. The second hydroxide ion attacks as a nucleophile to form a carbanion intermediate, which behaves as a base in the last step to yield the final product. 

A route based on a benzyne intermediate can afford the isoindole ring via a category lb process. iV-Cyanomethyl-Af-methyl-0-chlorobenzylamine cyclizes to 1-methylisoindole under the influence of potassium amide in liquid ammonia (equation 36) (77T581). The cyano group plays two important roles. First, it provides stabilization of the carbanion... 

Carbanions derived from side chain tertiary amides have also been cyclized to provide isoquinolones and isoindoles (equation 36).125 126 While benzyne intermediacy in the formation of the former is likely, the latter seems to arise through a SrnI reaction pathway. Synthesis of indole from the meta bromo compound (87), on the other hand, clearly involves an aryne cyclization. 27 A more versatile route to indoles is based on intramolecular addition of aminyl anions to arynes (equation 38).128 A somewhat similar dihydroindole preparation constitutes the first step in a synthesis of lycoranes (equation 39).129 The synthesis of (88) also falls in the same category of reactions, but it is noteworthy because only a few examples of ring closure of heteroarynes are mentioned in literature.27 28... 

The highly unstable and very reactive benzyne reacts with a second amide ion, creating a new carbanion. 

The latter is added to the benzyne. The initially formed carbanion is transformed by proton transfer to lithium-A N-diphenylamide, which upon aqueous workup undergoes protonation to give diphenylamine. 

Other stabilized carbanions suggested to react via the SRN1 process include the anions from 2,4,4-trimethyl-2-oxazoline, 2-benzy]-4,4-dimethyl-2-oxazoline, 2,4-dimethylthiazole, 2-benzyl-4,4-dimethylthiazole, and dimethyl methylphospho-nate [25]. Some examples are described in Scheme 10.13. Competition with a benzyne process has been determined in some of these reactions. 

Benzyne is an extremely reactive compound. It cannot be isolated and exists only for a very short time before it reacts. Under the strongly nucleophilic conditions of these reactions, a nucleophile adds to the bond to generate a carbanion. The strongly basic carbanion then removes a proton from some weak acid in the reaction mixture to form the final product. 

These two products can be explained by an elimination-addition mechanism, called the benzyne mechanism because of the unusual intermediate. Sodium amide (or sodium hydroxide in the Dow process) reacts as a base, abstracting a proton. The product is a carbanion with a negative charge and a nonbonding pair of electrons localized in the sp2 orbital that once formed the C—H bond. 

The carbanion can expel bromide ion to become a neutral species. As bromide leaves with its bonding electrons, an empty sp2 orbital remains. This orbital overlaps with the filled orbital adjacent to it, giving additional bonding between these two carbon atoms. The two sp2 orbitals are directed 60° away from each other, so their overlap is not very effective. This reactive intermediate is called a benzyne because it can be symbolized by drawing a triple bond between these two carbon atoms. Triple bonds are usually linear, however, so this is a very reactive, highly strained triple bond. 

Step 2 The carbanion expels the leaving group to give a benzyne intermediate. 

Notice the symmetry in this mechanism. Benzyne is formed from an ortho carbanion and it gives an ortho carbanion when it reacts with nucleophiles. The whole mechanism from bromobenzene to aniline involves an elimination to give benzyne followed by an addition of the nucleophile to the triple bond of benzyne. In many ways, this mechanism is the reverse of the normal addition-elimination mechanism for nucleophilic aromatic substitution and it is sometimes called the elimination-addition mechanism, the elimination step... 

Chapter 2 includes complete discussion on reaction intermediates including carboca-tions, carbanions, free radicals, carbenes, nitrines and benzynes. The structure, methods of generation and important reactions of all the intermediates are discussed in this chapter. The author has emphasized on their applications in the asymmetric synthesis. 

The Kametani group has made considerable use of the intramolecular trapping of benzynes by pendant carbanion centers. The nitrile (133) is a key and versatile intermediate in many of the K etani studies, including the preparation of optically pure estradiol. The ester of the benzocyclobutenecarboxylic acid (134) was prepared by a similar benzyne cyclization. The acid (134) was converted via oxidative decarboxylation and HCl hydrolysis to the very labile tra/t5-2-arylbenzocyclobutenol (135), which was used in the preparation of p ophyllotoxin. ... 

The elimination stage, in which benzyne is formed, involves two steps abstraction of a hydrogen ion (step 1) by the amide ion to form ammonia and carbanion I, which then loses halide ion (step 2) to form benzyne. 

The addition stage, in which benzyne is consumed, may also involve two steps attachment of the amide ion (step 3) to form carbanion II, v/hich then reacts with an acid, ammonia, to abstract a hydrogen ion (step 4). It may be that step (3) and step (4) are concerted, and addition involves a single step if this is so, the transition state is probably one in which attachment of nitrogen has proceeded to a greater extent than attachment of hydrogen, so that it has considerable carbanion... 

Which benzyne is this, and how is it that it yields m-anisidinc To deal with orientation—both in the elimination stage and the addition stage—we must remember that a methoxyi group has an electron-withdrawing inductive effect. Since the electrons in carbanions like 1 and 11 (pp. 836- 837) are out of the plane of the 7T cloud, there is no question of resonance interaction only the inductive effect, working along the a bonds (or perhaps through space), is operative. 

Here benzyne formation involves abstraction of a proton (reaction 5) by the base QH5 to form a carbanion which loses fluoride ion (reaction 6) to give benzyne. 

Addition of phenyllithium (reaction 7) to the benzyne gives the organolithium compound IV. From one point of view, this is the same reaction sequence observed for the amide ion-ammonia reaction (above), but it stops at the carbanion stage for want of strong acid. (Alternatively, the Lewis acid Li has completed thp sequence.) Addition of water—in this company, a very strong acid -yields (reaction 8) the final product. (The strong acid has displaced the weaker acid Li .)... 

Phenylation of carbanions derived from olefins such as 1,3-pentadiene and l-(p-anisyl) propene and aromatics such as indene and fluorene are possible by the SrnI route in ammonia solvent. From the 1,3-pentadiene a mixture of mono-olefins and dienes is produced along with a small amount of di- and triphenylated material. Hydrogenation of the mixture gives 1-phenylpentane in 74% yield.106) Phenylation of 2- and 4-picolyl anions is conveniently effected in ammonia. When bromo- or iodobenzene is used for this purpose, reaction probably occurs by both SrnI and benzyne routes.111)... 

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