Diethylzinc conjugate addition

Chiral diaminocarbene complexes of copper were used in asymmetric conjugate addition of diethylzinc to Michael acceptors. Achiral copper carbene complexes derived from imidazolium salts were synthesized and characterized for the first time by Arduengo in 1993 [43]. In 2001, Woodward reported the use of such Arduengo-type carbene in copper-catalyzed conjugate addition and showed their strong accelerating effect [44]. The same year, Alex-... 

On the other hand, S/O ligands have been developed to a lesser extent, but their efficient use as chiral ligands was proven in the enantioselective addition of diethylzinc to aldehydes and also in the copper-catalysed asymmetric conjugate addition. 

Figure 83 Examples of well-defined Cu-containing enantiopure complexes used in conjugate addition reactions with diethylzinc.82...

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

Ojima and co-workers found that chiral monodentate phosphoramidite (S,R,R)-35 was highly effective for the enantioselective conjugate addition of diethylzinc to acyclic nitroalkenes (up to 99% ee).86... 

In the conjugate addition of diethylzinc to enones catalyzed by copper reagent CuOTf or Cu(OTf)2 in the presence of 90, an ee of over 60% has been obtained. Study also shows that the actual catalyst in the reaction may be a Cu(I) species formed via in situ reduction of Cu(II) complexes. 

Phosphite compounds, which have been discussed in the context of their application in asymmetric hydrogenation reactions (see Section 6.1.2.6), can also be used to effect the copper salt-mediated asymmetric conjugate addition of diethylzinc to enones.74 As shown in Scheme 8-33, in the presence of diphosphite 92 and copper salt [Cu(OTf)2], the asymmetric conjugate addition proceeds smoothly, giving the corresponding addition product with high conversion and ee. In contrast, the monophosphite 93 gave substantially lower ee. 

Sewald and Wendisch (170) applied the Feringa system to the conjugate addition of diethylzinc to nitroolefins. Optimal selectivities were found for the acetal-substituted nitroethylene (234) providing adduct 235 in 86% ee and quantitative conversion, Eq. 136. 

Tomioka and co-workers (175) showed that monodentate aminophosphines are moderately effective in mediating the conjugate addition of diethylzinc to enones. The precatalyst is generated from Cu(OTf)2 and 2 equiv of phosphine 240. Optimal selectivities are obtained in the conjugate addition of diethylzinc to dimethylcyclo-hexenone, affording the adduct in 70% ee and 80% yield, Eq. 141. 

In a comprehensive screen of the effect of TADDOL and BINOL-derived phosphites on the conjugate addition of diethylzinc to representative enones, Al-exakis et al. (181) revealed that the Feringa ligand exhibits the broadest scope, providing the conjugate adducts in selectivities ranging from 66 to 92% ee, Eq. 144. 

The first application of a copper-catalyzed conjugate addition of diethylzinc to 2-cyclohexenone, using chiral phosphorous ligand 12, was reported by AlexaHs (Fig. 7.1) [35]. An ee of 32% was obtained. 

Simple organozinc reagents, such as diethylzinc, undergo conjugate addition with... 

A combined system consisting of a Ni(ll) complex and (2S)-DAIB effects the conjugate addition of diethylzinc to chalcone, resulting in the formation of (R)-1,3-diphenylpenta-1-one in 85% ee.°... 

Copper-Catalyzed Enantioselective Conjugate Addition of Diethylzinc to Enones... 

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. 

Enantioselective conjugate addition of diethylzinc proceeds in the presence of №( ) complex104. Asymmetric amplification was observed in reactions using chiral ligand l156, 66157, 47107 and 3 (equation 38)109. 

Three approaches to zinc enolates are commonly adopted the process associated to the classical Reformatsky reaction is based on the insertion of Zn(0) into the carbon—halogen bond of an a-haloester. Two additional routes involve (i) transmetallation of a lithium enolate with a Zn(II) salt (Section V.A) and (ii) the transition-metal-catalysed conjugate addition of diethylzinc to Michael acceptors (Section V.B). 

Soai [8], Bolm [9], Feringa [10], and Alexakis [11] have reported nickel-or copper-catalyzed asymmetric conjugate addition of diethylzinc, with chiral amino alcohols or a chiral trivalent phosphorus compound (Scheme 8D.2). 

A highly enantioselective synthesis of a-dehydroamino acids (186) with a stereogenic centre at the y -position has been developed, which employs a copper-catalysed asymmetric conjugate addition of diethylzinc to a,j3-unsaturated imines (185) with the TADDOL-derived phosphoramidite (187) as a chiral ligand.234... 

The asymmetric conjugate addition of arylalkynes ArC=CH to nitroalkenes can be mediated by dimethylzinc (or diethylzinc) and (l/f,2/J)-2-(dimethylamino)-l,2-diphenylethanol as chiral ligand in toluene the resulting products were obtained in high ee (<99%) and good yields. The presence of 0.03 equiv. of galvinoxyl improved the reaction yield.259... 

Enantioselective addition (C H Zn with enones.1 In the presence of (1S,2R)-1 (1 equiv.), diethylzinc undergoes conjugate addition to enones to form (R)-P-ethyl ketones in 81-94% ee. Use of catalytic amounts of 1 decreases the enantioselectivity to 60-80% ee. 

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