Dialkylzinc compounds conjugate addition

Woodward et al. have used the binaphthol-derived ligand 40 in asymmetric conjugate addition reactions of dialkylzinc to enones [46]. Compound 40 has also been studied as a ligand in allylic substitutions with diorganozinc reagents [47]. To allow better control over selectivity in y substitution of the allylic electrophiles studied, Woodward et al. investigated the influence of an additional ester substituent in the jS-position (Scheme 8.25). 

Meanwhile, copper salt catalyzed asymmetric conjugate addition of dialkylzincs has been developed. Alexakis and coworkers reported the catalytic addition of diethylzinc to cyclohexenone using copper salt111. Feringa and coworkers developed a marvelous phosphoramidite (49)112. In the presence of 49 and Cu(OTf)2, diethylzinc adds to cyclohexenone in >98% . Recently, asymmetric addition of diphenylzinc using 49 has been reported113. Nowadays, compounds 50114, 51115, 52116, 53117 and 54118 are known as highly enantioselective catalysts. 

Dialkylzinc derivatives are inert towards conjugated enones (e.g. 181) in hydrocarbon or ethereal solvents. The discovery that a conjugate addition can be promoted by Cu(I) salts in the presence of suitable ligands L (e.g. sulphonamide 182) opened a new route to zinc enolates (e.g. 183), and hence to the development of three-component protocols, such as the tandem 1,4-addition/aldol addition process outlined in equation 92186. If the addition of the aldehyde is carried out at —78 °C, the single adduct 184 is formed, among four possible diastereomeric products. The presence of sulphonamide is fundamental in terms of reaction kinetics its role is supposed to be in binding both Cu(I) and Zn(II) and forming a mixed metal cluster compound which acts as the true 1,4-addition catalyst. 

In another study Feringa et al. [20] reported a catalytic enantioselective three-component tandem conjugate addition-aldol reaction of dialkyl zincs. Here, zinc enolates were generated in situ via catalytic enantioselective Michael addition of dialkylzinc compounds to cydohexenone in the presence of a chiral Cu catalyst. Their diastereoselective reaction with an aldehyde then gave trans-2,3-disubstituted cyclohexanones in up to 92% yields and up to >99% ees (Scheme 9.11). 

Organozinc compounds add to conjugated systems. The use of chiral ligands is effective for conjugate addition of diaUcylzinc compounds to a,p-unsaturated ketones, esters, and so on, including conjugated lactones." Many dialkyl-zinc compounds can be used, including vinylzinc compounds.Dialkylzinc... 

The enantioselective addition of dialkylzinc reagents to alkynyl aldehydes catalysed by ( )-(+)-(l-methylpyrrolidin-2-yl)diphenylmethanol has been described. Thus the laevorotatory alcohol 102 was obtained in 78% enantiomeric excess (equation 15). The action of diethylaluminium chloride on alkynyllithium compounds yields ether-free diethylalkynylalanes 103, which undergo conjugate addition to nitroalkenes (equation 16). Conjugate addition also occurs in the reactions of (l-alkynyl)diisopropoxyboranes 104 (R = Bu, t-Bu or Ph) with a,j5-unsaturated ketones 105 (R = H, Me or Ph R = Me, hexyl or Ph) (equation 17). ... 

The preparation of silyl enol ethers from carbonyl compounds represents one of the major uses of TMSOTf. Recently, the stereochemistry and regiospecificity of such transformation has been addressed for aldehydes and -(iV-alkoxycarbonylamino) ketones, respectively. On the other hand, enantiopure silyl enol ethers can be formed by addition of TMSOTf to zinc enolates, which are obtained from the copper-catalyzed enantioselective conjugate addition of dialkylzinc reagents to cyclic (eq 36) and acyclic enones. ... 

Dual enantioselective control in the Cu-catalysed conjugate addition of dialkylzinc compounds to acyclic and cyclic enones has been realized in the presence of functionalized A -heterocyclic carbene ligands. " For example, a high degree of asymmetric catalysis (up to 96% ee) has been achieved using a (hydroxy amide)-functionalized azolium salt (19). Most likely the selectivity appears because of the facial selection of the enone, which is a result of steric repulsion between the alkyl group on the azolium ring and the alkyl substituent at the / -position of the enone. 

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