Reaction with a carbanion

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

Carboxylation (Section 19 11) In the preparation of a car boxyhc acid the reaction of a carbanion with carbon diox ide Typically the carbanion source is a Gngnard reagent... 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

More general procedures for additions of halogen fluorides to highly fluori-nated olefins involve reactions with a source of nucleophilic fluoride ion, such as an alkali metal fluoride, in the presence of aposttive halogen donor [62 107, lOff, 109, 110, 111] (equations 11 and 12) These processes are likely to occur by the generation and capture of perfluorocarbamonic intermediates Tertiary fluormated carbanions can be isolated as cesium [112], silver [113], or tns(dimethylamino)sul-... 

We examined the possibility of a direct formation of two C-C bonds by reaction of a carbanion with [Fe(arene)2]2+ in which the arene bears methyl groups. We could indeed repeat Hellings s experiments but found that mesitylene was the only aromatic allowing this possibility in reasonable yields. With p-xylene, a low yield of an unstable complex was obtained corresponding to double nucleophilic attack of phenyllithium on the same ring in spite of the bulk of the methyl groups [23]. Eq. (4) ... 

Corey and Chaykovsky had discovered that dimethyl sulfoxide is converted to methyl-sulfinyl carbanion upon treatment with sodium hydride114 and that this conjugate base of DMSO reacts with various electrophiles115. This finding has opened up various reactions with a-sulfmyl carbanions derived from sulfoxides, since the sulfinyl function can be removed either by thermolysis or by subjecting the compound to reductive desulfurization. Thus a-sulfmyl carbanions have become versatile synthetically useful reagents. 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

In the second approach55 an allylsilane was employed as carbon nucleophile in the side chain. Allylsilanes have been frequently used as masked allyl carbanions, usually in reactions with a keto function57. Palladium-catalyzed reaction of allylsilane 57 with LiCl under similar conditions as used for the other intramolecular 1,4-oxidations afforded 58 (equation 22). Interestingly, the carbochlorination over the diene was highly 1,4-syn... 

In anionic polymerisation p-electrons of the monomers are attached by negatively charged ion, an anion, so the anionic polymerisation is initiated by a negative ion or anion. An anion generates a carbanion on reaction with a monomer and carbonion is an active centre which propagates the reaction. 

Silylation using the silylacetate (3.1.14) [49] involves the initial formation of the acetate carbanion, which abstracts a proton from the carbonyl compound or alcohol (Scheme 3.2, Table 3.5). When the reaction with a ketone is conducted in the presence of an aldehyde, crossed aldol products are obtained (see Chapter 6). 

Figure 6.8 Reaction of a carbanion-terminated polymer with an acetylated wood surface to graft a polymer on to the wood surface.

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

Since the basic or carbanion intermediate can continue to go to product by Steps 2 and 3, we have a chain reaction which is consistent with the rapid isomerizations which may be obtained using these catalysts. This mechanistic interpretation was proposed in one of the first papers published on this subject (5) it and similar interpretations have been very helpful in bringing about an understanding of base-catalyzed reactions. The chain-reaction sequence may be terminated by reaction with a formation of a material which is not basic enough to metallate the olefin. Such compounds may be polyunsaturated hydrocarbons which may be formed by elimination of hydride ions from a carbanion. 

The carbanions thus produced in situ have only a transient existence because of the more acidic materials present, such as the ketones, acids, and condensation products produced. However, they are effective for a reaction with a relatively large driving force, such as limonene dehydrogenation. 

Next, you need to determine how to produce the ester in Figure 17-3. (This is a (3-dicarbonyl compound like the starting material. This relationship may be important.) One way to produce this ester is shown in Figure 17-4. This step requires you to start with a carbanion, which can form through the reaction of a strong base with a (3-dicarbonyl compound. This step is in Figure 17-5. We use the t-butoxide ion as the base, but other bases are acceptable. 

The benzotriazole moiety of iV-(a-aminoalkyl)benzotriazoles is readily replaced by hydride upon reduction with sodium borohydride, or with a carbanion by reaction with Grignard or lithium reagents. These are two most important reactions of benzotriazole derivatives from which versatile routes have been developed for the synthesis of primary, secondary, and tertiary amines. 

The use of strong bases such as sodamide in liquid ammonia, lithium diisopropylamide and the alkyl- and aryl-lithiums gives essentially quantitative deprotonation at a side-chain alkyl group. The carbanions produced can undergo reactions with a wide range of electrophiles, as exemplified in Scheme 55. 

A somewhat different approach to this series of compounds involves the reaction between a carbanion and an aromatic nitrile. Thus, a series of methylpyrazines 253 is first treated with lithium diisopropylamide (LDA) to generate an anion at the methyl group. Addition of an aromatic nitrile produces 254 (Equation 89) <2003JME222, 2004EUP1388541>. Many other examples have been reported <2003JME222>, including some with substituents at the open position in structure 254. 

It is well known that base-induced elimination reactions can proceed either by a single, concerted step (E2), or by two steps, proton transfer and leaving group expulsion, with a carbanion intermediate (ElcB) to yield an alkene. " The... 

Reaction of that with potassium tert-butoxide affords the corresponding carbanion this is thought to first add to the enone in (5-3). The anion from the reaction with a second equivalent of base then adds to the enone function to form the spiw ring. The fact that the product from this reaction has the same relative stereochemistry as the natural product is attributed to the better overlap of the enolate with the triple bond in the transition state leading to that isomer. The product from the reaction is thus + griseo-fulvin (5-6) [5]. 

However, difluoromethylation occurs when nucleophiles intercept difluoro-carbene generated under basic conditions, providing a route to difluoromethyl-ethers of phenols [33] and thiophenols [34]. The reaction with phosphite anion leads to the corresponding difluoromethyl phosphonate (see Sect. 2.3.2) while nucleophilic carbanions such as alkynes [35] also undergo formal alkylation, as do malonates [36,37]. An -difluoromethylaziridine was reported in a reaction with a glycine imine [38]. The scope of the established chemistry is summarised in Fig. 1. Bromodifluoromethylation occurs with a similar range of nucleophiles [39,40], and also with carbonyl-stabilised carbanions such as malonates [41,42]. 

---