Carbanion electrophilic substitution

Electrophilic Substitution of A,A,-Diethyl-5-phenyl-3//-azepin-2-amine Carbanion General Procedures 38... 

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

This reaction, for which the termprototmpic rearrangement is sometimes used, is an example of electrophilic substitution with accompanying allylic rearrangement. The mechanism involves abstraction by the base to give a resonance-stabilized carbanion, which then combines with a proton at the position that will give the more... 

In Section 4.5 we discussed reactions in which electrophilic substitution of a metal ion takes place by a bimolecular pathway. The unimolecular substitution is less common, although there are some examples in cases where the carbanion is well stabilized.120 For our purposes here the most important SE1 reactions are those in which the leaving group is a proton or a neutral carbon molecule. 

For a review of electrophilic substitution and the carbanion field, see D. J. Cram, Fundamentals of Carbanion Chemistry, Academic Press, New York, 1965. 

If R is an alkyl group, reaction (1) leads to the familiar mechanism of nucleophilic substitution at saturated carbon whilst reaction (2) leads to an electrophilic substitution of saturated carbon. Of course for these mechanisms to be followed it is not necessary for a completely developed carbonium ion or carbanion to be formed, and both nucleophilic and electrophilic substitution at saturated carbon may proceed by mechanisms in which the carbon atom undergoing substitution has a carbonium ion character or a carbanion character respectively. 

When an electrophilic substitution at saturated carbon occurs, either a car-banion is liberated as such or, if no carbanion is actually formed, the carbon atom undergoing substitution has a certain amount of carbanion character . Thus a knowledge of the factors governing the formation and the stability of carbanions might be of help in the understanding of the mechanism of electrophilic substitution at saturated carbon. 

Arenes usually undergo electrophilic substitution, and are inert to nucleophilic attack. However, nucleophile attack on arenes occurs by complex formation. Fast nucleophilic substitution with carbanions with pKa values >22 has been extensively studied [44]. The nucleophiles attack the coordinated benzene ring from the exo side, and the intermediate i/2-cvclohexadienyl anion complex 171 is generated. Three further transformations of this intermediate are possible. When Cr(0) is oxidized with iodine, decomplexation of 171 and elimination of hydride occur to give the substituted benzene 172. Protonation with strong acids, such as trifluoroacetic acid, followed by oxidation of Cr(0) gives rise to the substituted 1,3-cyclohexadiene 173. The 5,6-trans-disubstituted 1,3-cyclohexadiene 174 is formed by the reaction of an electrophile. 

First, the preparation of the substituted benzene 172 is explained. In the reaction of substituted benzene complex 175 with carbanions, the meta orientation to give 176 is observed even in the presence of ortho- and para-orienting electron-donating groups, such as methoxy and amino groups [45], Using this property, the nucleophilic substitution reaction, complementary to ordinary electrophilic substitution reaction, is... 

Carbanion-electrophile disconnections Disconnection should normally occur adjacent to an electron withdrawing group. In each case, one of the compounds derived from the synthon should be able to form a carbanion whilst the structure of other should contain an electrophilic centre. Reconnection is by means of a suitable carbanion substitution or condensation reaction. 

Hydrogen exchange reactions of heteroaromatics64 69, 65 carried out in strongly alkaline media, such as potassium amide/liquid ammonia, alcoholic solutions of alkoxides, or solutions of potassium <-butoxide in dimethyl sulfoxide, proceed through an entirely different mechanism (sometimes called protophilic ) involving a carbanion-type intermediate66, 67 they are not electrophilic substitutions as such and will not be treated in this review. 

Many reactions become possible only in such superbasic solutions, while others can be carried out under much milder conditions. Only some examples of preparative interest (which depend on the ionization of a C—H or N—H bond) will be mentioned here. The subsequent reaction of the resulting carbanion may involve electrophilic substitution, isomerization, elimination, or condensation [321, 322]. Systematic studies of solvent effects on intrinsic rate constants of proton-transfer reactions between carbon acids and carboxylate ions as well as amines as bases in various dimethyl sulfoxide/ water mixtures have been carried out by Bernasconi et al. [769]. 

The author believes that students are well aware of the basic reaction pathways such as substitutions, additions, eliminations, aromatic substitutions, aliphatic nucleophilic substitutions and electrophilic substitutions. Students may follow undergraduate books on reaction mechanisms for basic knowledge of reactive intermediates and oxidation and reduction processes. Reaction Mechanisms in Organic Synthesis provides extensive coverage of various carbon-carbon bond forming reactions such as transition metal catalyzed reactions use of stabilized carbanions, ylides and enamines for the carbon-carbon bond forming reactions and advance level use of oxidation and reduction reagents in synthesis. 

Such a dethroning of carbocations and carbanions can be carried another step further. Certain purely covalent compounds possessing weakly polarized bonds can serve as ionic reagents if their electronic system is highly polarizable. In such molecules the approach of a charged particle, or even a dipole, induces a significant displacement of electrons. The electron displacement is to such an extent that the reaction intermediates may become almost fully ionized, as if an ionic reagent had been actually used. A typical example is represented by the previously mentioned reactions of electrophilic substitution in aromatic series, where a neutral molecule of an aromatic hydrocarbon, ArH, behaves as an efficient equivalent to a carbanion, Ar . 

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