Conjugate addition carbanions generated

Selenium-stabilized carbanions can be also generated by 1,4-addition of nucleophilic reagents to a-selanyl a,[3-unsaturated carbonyl compounds. The conjugate addition of trialkylsilyllithium compounds to 133, followed by reaction with allyl iodide, afforded the addition products 134 with good m-stereoselectivity (R = Me dr 86 14 R = Ph dr 94 6) (Scheme 34).214 The addition of lithium dialkylcuprates to 2-phenylselanylcycloalk-2-enones has also been used for the synthesis of natural products.215,216... 

Majetich showed that fluoride generated carbanions undergo Michael-type additions. 22 jq achieve conjugate addition with carbanions generated from silanes usually requires the use of DMF as a solvent, and HMPA is often added to obtain satisfactory yields. In this example, 747 was treated with TBAF to generate the carbanion 748. Intramolecular Michael addition and hydrolysis led to the bicyclic product 749. ... 

The chromium complexes of styrene and the related arenes can be susceptible to nucleophilic addition at the p-position of the double bond. The conjugate addition of nucleophiles at the p-position generates the tricarbonylchromium-stabilized benzylic carbanion and the generated benzylic carbanion could be further trapped with electrophiles. An intramolecular cyclization to the chromium complexed styrene double bond gave tricyclic compound (Eq. 4) [4]. 

The role of the trimethylsilyl group is to stabilize the intermediate carbanion formed by conjugate addition. The silyl group is removed under conditions similar to those required for the dehydration the removal occurs by nucleophilic attack on silicon, resulting in displacement of the ketone. The advantage of the substituted methyl vinyl ketone is that it permits the annelation reaction to be carried out in aprotic solvents under conditions where enolate equilibration does not take place. The annelation of unsymmetrical ketones can therefore be controlled by using specific enolates generated by the methods described in Chapter 1. 

Activated alkynes react with nucleophiles by conjugate addition, and the carbanion thus generated can be quenched with electrophiles, in this case acid. 

An alkoxyallylation of activated olefins is shown in Scheme 16. Conjugate addition of the generated alkoxide gives rise to the stabilized carbanion, which attacks the 17 -allylpalladium complex.f ... 

Novel variants on established carbanion routes to cyclopentanes include the use of thio-esters in a Dieckmann cyclization" (which proceeds under milder conditions than the parent reaction), an intramolecular displacement involving transfer of chirality to the ring being formed [(59) - (60)], and a case where the carbanion is generated by conjugate addition of an organolithium reagent to an... 

The conjugate addition of a carbanionic species across the activated double bond, such as in the esters of maleic and fumaric acid, are typical examples of Michael addition. Carbanions are usually generated using a base catalyst and, hence, reaction of MA itself has not been attempted. A representative example of the addition of diethyl malonate 74 to diethyl maleate, which produces the tetracarboxylic ester 75, is shown below. 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

In general these reactions are base-catalysed in that it is necessary to remove a proton from HCXYZ in order to generate the carbanion, eCXYZ, the effective nucleophile one or more of X, Y and Z are usually electron-withdrawing in order to stabilise it. The initial adduct (84) acquires a proton from the solvent (often H20 or ROH) to yield the simple addition product (85). Whether or not this undergoes subsequent dehydration (86) depends on the availability of an H atom, either on an a-carbon or where X, Y or Z = H, and also on whether the C=C so introduced would, or would not, be conjugated with other C=C or C=0 linkages in the product ... 

Reduction of benzenoid hydrocarbons with solvated electrons generated by the solution of an alkali metal in liquid ammonia, the Birch reaction [34], involves homogeneous electron addition to the lowest unoccupied 7t-molecular orbital. Protonation of the radical-anion leads to a radical intermediate, which accepts a further electron. Protonation of the delocalised carbanion then occurs at the point of highest charge density and a non-conjugated cyclohexadiene 6 is formed by reduction of the benzene ring. An alcohol is usually added to the reaction mixture and acts as a proton source. The non-conjugated cyclohexadiene is stable in the presence of... 

We have presented evidence that pyrrole-2-carboxylic acid decarboxylates in acid via the addition of water to the carboxyl group, rather than by direct formation of C02.73 This leads to the formation of the conjugate acid of carbonic acid, C(OH)3+, which rapidly dissociates into protonated water and carbon dioxide (Scheme 9). The pKA for protonation of the a-carbon acid of pyrrole is —3.8.74 Although this mechanism of decarboxylation is more complex than the typical dissociative mechanism generating carbon dioxide, the weak carbanion formed will be a poor nucleophile and will not be subject to internal return. However, this leads to a point of interest, in that an enzyme catalyzes the decarboxylation and carboxylation of pyrrole-2-carboxylic acid and pyrrole respectively.75 In the decarboxylation reaction, unlike the case of 2-ketoacids, the enzyme cannot access the potential catalysis available from preventing the internal return from a highly basic carbanion, which could be the reason that the rates of decarboxylation are more comparable to those in solution. Therefore, the enzyme cannot achieve further acceleration of decarboxylation. In the carboxylation of pyrrole, the absence of a reactive carbanion will also make the reaction more difficult however, in this case it occurs more readily than with other aromatic acid decarboxylases. 

The butyllithium-generated anion of an allylic sulfone was reported to add to conjugate enones, but different regioselectivity was observed for 2-cyclohexenone (1,4-y) and 3-penten-2-one (1,4-a), as shown in equation (31). Clean 1,4-a additions to both acyclic and cyclic enones can be realized when the lithio carbanions are allowed to react in the presence of HMPA (2 mol equiv.) at -78 C. Under these conditions, allyl phenyl sulfone reacts with 2-cyclohexenone. 2-methyl-2-cyclopentenone and 3-methyl-2-cyclohexenone, giving the corresponding 1,4-a adducts as a 75 25 mixture of two dia-stereoisomers. In the reaction of allylic phenyl sulfone with an acyclic enone, 4-methyl-3-penten-2-one,... 

The nucleophilic addition of a carbanion to an aldehyde or a ketone having a conjugated double bond and the subsequent dehydration sequence (Knoevenagei reaction) is a popular method for generating dienes and polyenes (equation 37). This reaction takes place efficiently and stereoselectively, when LDA is used as a base in the presence of chlorotrimethylsilane (equation 38). Knoevenagei condensation was a key reaction during many classical carotenoid syntheses. Recently, Seltzer and coworkers used the dimefiiyl acetal of acetylacetaldehyde for aldol condensation with a Cis-aldehyde, to generate the tetraenyl ketone acetal (equation 39). ... 

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