Addition, of carbanions

Alcohols can be synthesized by the addition of carbanions to carbonyl compounds (W.C. Still, 1976) or epoxides. Both types of reactions often produce chiral centres, and stereoselectivity is an important aspect of these reactions. 

Addition of Carbanions to a B Unsaturated Ketones The Michael Reaction... 

ADDITION OF CARBANIONS TO a, p-UN SATURATED KETONES THE MICHAEL REACTION... 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

The first report on the addition of carbanions a-substituted by a chiral sulfinyl group to carbonyl functions described the reaction with symmetrical ketones3. It was found that meta-lation of ( + )-(S)-(methylsulfinylmethyl)benzene followed by quenching with acetone gives a mixture of diastereomeric /i-hydroxysulfoxides in a 15 1 ratio. This ratio depends on the presence or absence of extra lithium salts i.c., the source of the mcthyllithium used in deprotonation67. 

High diastereoselectivity is attained only on addition of carbanions of 1-sulfinylalkenes to highly hindered aldehydes13 (see Table 4). 

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

Decarboxylations can be regarded as reversals of the addition of carbanions to carbon dioxide (16-33), but free carbanions are not always involved. When the carboxylate ion is decarboxylated, the mechanism can be either Sgl or Se2. In the... 

On the other hand, the enantioselective 1,4-addition of carbanions such as enolates to linear enones is an interesting challenge, since relatively few efficient methods exist for these transformations. The Michael reaction of p-dicarbonyl compounds with a,p-unsaturated ketones can be catalysed by a number of transition-metal compounds. The asymmetric version of this reaction has been performed using chiral diol, diamine, and diphosphine ligands. In the past few years, bidentate and polydentate thioethers have begun to be considered as chiral ligands for this reaction. As an example, Christoffers et al. have developed the synthesis of several S/O-bidentate and S/O/S-tridentate thioether... 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

Axial addition to cyclohexanones.1 Addition of carbanions to cyclic ketones generally favors equatorial products. This preference may result from nonbonded interactions, since Trost et al. now find that the addition of LiCH2CN to cyclohexanones is axial selective (equation I). The preference for axial addition is even higher in the case of cyclohexenones ( 20 1). The axial selectivity of LiCH2CN is... 

Other reactions involving the addition of carbanions are reactions like Perkin s reaction, Claisen condensation, benzilic acid rearrangement and Michael addition. 

Addition of carbanions (which may be electrochemically generated), derived from active methylene compounds (such as fluorene or indene193), to nitrosobenzene produces the intermediate181 70, which is dehydrated to the azomethine 71 or may be oxidized to the nitrone derivative 72, as illustrated by Scheme 8. 

Examples of the Michael-type addition of carbanions, derived from activated methylene compounds, with electron-deficient alkenes under phase-transfer catalytic conditions have been reported [e.g. 1-17] (Table 6.16). Although the basic conditions are normally provided by sodium hydroxide or potassium carbonate, fluoride and cyanide salts have also been used [e.g. 1, 12-14]. Soliddiquid two-phase systems, with or without added organic solvent [e.g. 15-18] and polymer-supported catalysts [11] have been employed, as well as normal liquiddiquid conditions. The micellar ammonium catalysts have also been used, e.g. for the condensation of p-dicarbonyl compounds with but-3-en-2-one [19], and they are reported to be superior to tetra-n-butylammonium bromide at low base concentrations. 

Carbonylation (continued) of secondary alcohols, 34 94-96 (HRhIjCCO)] as active catalyst, 34 95 inhibitory effect of CO pressure, 34 94 2-propanol, 34 94 deuterium studies, 34 95 Carbonyl groups, addition of carbanions, 35 390-392... 

The addition of carbanions, generated electrochemically by reduction of the carbon-halogen bond, to carbon dioxide has been examined under a variety of experimental conditions. Direct electrosynthesis of carboxylic acids in a divided cell using an aprotic solvent and a tetraalkylammonium salt as electrolyte is most sue-... 

There are a few reports on the use of oximes as electrophilic amination reagents. Since 1984, ketone O-sulfonyloxknes have found applicability as amino transfer reagents to car-banions. In the reaction of organometaUic compounds with oximes, carbanions attack the carbonyl carbon of the oxime, giving Af-substituted hydroxylamines as addition products (Scheme 53, path a). However, a number of scattered reports have been also published on the formation of aziridines by a-deprotonation, followed by addition (path b) or formation of azirines by a-deprotonation before addition (path c). Addition of carbanions to azirines also yields aziridines, which are hydrolyzed to a-aminoalcohols. 

Another important reaction in synthetic chemistry leading to C-C bond formation is the Michael addition. The reaction typically involves a conjugate or nucleophilic 1,4-addition of carbanions to a,/l-unsaturated aldehydes, ketones, esters, nitriles, or sulfones 157) (Scheme 21). A base is used to form the carbanion by abstracting a proton from an activated methylene precursor (donor), which attacks the alkene (acceptor). Strong bases are usually used in this reaction, leading to the formation of byproducts arising from side reactions such as condensations, dimerizations, or rearrangements. 

Several other examples of conjugate addition of carbanions carried out under kinetically controlled conditions are given in Scheme 1.12. 

Michael-Additions The most important application of this type of reaction is the carbon-carbon bond formation p to a carbonyl function by the addition of carbanion. The asymmetric version of the Michael-addition has been known since 1973. An optically active vinyl sulfoxide served as chiral auxiliary198). 

In view of the smooth addition of carbanions to the electrophilic P atom of phosphorins (see p. 78 and 66), Markl and Merz attempted the addition of carbenoids (carbenes ) by reacting dichloromethane, trichloromethane or dichloro-phenylmethane with potassium-tert-butoxide in the presence of 2.4.6-triphenyl-X -phosphorin 22 or 2.4.6-tri-tert-butyl-X -phosphorin 24. The desired bicyclocompound 7/5 or the X -phosphepin 116 were not obtained. Instead, benzene derivatives were formed by loss of a PCI fragment, the fate of which was not determined. Markl has proposed a mechanism in which intermediates 114,115 and 116 ZK invoked ... 

Decarboxylations can be regarded as reversals of the addition of carbanions to carbon dioxide (6-32), but free carbanions are not always involved.471 When the carboxylate ion is decarboxylated, the mechanism can be either SeI or Se2. In the case of the SeI mechanism, the reaction is of course aided by the presence of electron-withdrawing groups, which stabilize the carbanion.472 Decarboxylations of carboxylate ions can be accelerated by the addition of a suitable crown ether, which in effect removes the metallic ion.473 The reaction without the metallic ion has also been performed in the gas phase.474 But some acids can also be decarboxylated directly and, in most of these cases, there is a cyclic, six-center mechanism ... 

Another route to anthraquinones has been devised which relies on the addition of carbanions (22) derived from phthalides to arynes (81JCS(P1)2120). For the formation of anthraquinone (23) itself, phthalide was treated with 2.2 equivalents of lithium diisopropyl-amide in THF. Bromobenzene was then added and the reaction mixture warmed to room... 

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