Conjugate addition reactions lithium enolate synthesis

The conjugate addition of lithium bis(phenyldimethylsilyl)cuprates to tt./t-unsaUi rated esters forms enolates, which readily react with aldehydes to give 2-substituted 3-silyl esters (equation 129)509. The products are useful as intermediates in the synthesis of allylsilanes and natural products. Yields of this reaction may be significantly increased by... 

Whatever the exact mechanism of the conjugate-addition reaction, it seems clear that enolate anions are formed as intermediates and they can be trapped as the silyl enol ether or alkylated with various electrophiles. For example, addition of lithium methylvinyl cuprate (a mixed-cuprate reagent) to cyclopentenone generates the intermediate enolate 166, that can be alkylated with allyl bromide to give the product 167 (1.161). The trans product often predominates, although the transxis ratio depends on the nature of the substrate, the alkyl groups and the conditions and it is possible to obtain the cis isomer as the major product. Examples of intramolecular trapping of the enolate are known, as illustrated in the formation of the ds-decalone 168, an intermediate in the synthesis of the sesquiterpene valerane (1.162). 

Michael additions. Gerlach and Kiinzler report that the lithium enolate of S-t-butyl thioacetate undergoes 1,4-addition to cyclopentenone. They have extended this Michael reaction to a synthesis of methyl jasmonate (5), based on the similar conjugate addition of the trimethylsilyl enolate 1 promoted by tetra-n-butylam-monium fluoride. The adduct 2 was alkylated by l-bromo-2-pentyne in the presence of tetra-n-butylammonium fluoride to give 3 in rather low yield. Remaining steps to 5 were methanolysis and partial hydrogenation of the triple bond. 

Related a,p-Unsaturated Esters. Similar a,p-unsaturated esters bearing a heterocyclic chiral auxiliary of a-amino acid origin at the p-position are known and have been utilized in asymmetric synthesis. Effective asymmetric conjugate additions of cuprates to (2), (3), and (5)J epoxidations of (3), and dipolar cycloadditions of (2) have been reported. Although oxazoli-dine (4) is only obtained as an 86 14 equilibrating mixture of stereoisomers, reactions with the lithium (Z)-enolate of methyl N-benzylideneglycinate (see Ethyl N-Benzylideneglycinate) are exclusively diastereoselective. 

The protection of an a, p-unsaturated ketone by a conjugate addition strategy is the subject of our last example but it does not involve the use of an 0,0-acetal. During a synthesis of the cockroach pheromone Periplanone B. Still needed to perform a copper(I)-mediated Sn2 reaction on the allylic acetate 37.1 [Scheme 2.37], In order to prevent competing addition to the a, p-unsaturated ketone, it was protected temporarily by conjugate addition of trimethylstannyl-lithium and trapping of the intermediate enolate with chlorotrimethylsilane. The desired Sn2 reaction was then performed on the adduct 37.2 and the a.p-un-saturated ketone recovered by oxidation of the C-Sn bond to a C-OH using m-chloroperbenzoic acid. Concomitant destruction of the labile enol ether and -elimination of water returned the a, p-unsaturated ketone 373. 

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