Copper Catalyzed Dialkylzinc Additions

Since the stability of N phosphinoyl imines derived from enolizable aldehydes can be problematic, an in situ formation of the N phosphinoyl imine from its 

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Scheme 5.108 Simplified tentative catalytic cycle of the copper-catalyzed conjugate addition of dialkylzinc to cyclohexenone.

A summary of other chiral ligands with corresponding enantioselectivities in the copper-catalyzed 1,4-addition of dialkylzinc to cyclic enones is shown in Figure 5.55-58... 

The use of vinyl epoxides as substrates in enantioselective copper-catalyzed reactions, on the other hand, has met with more success. An interesting chiral ligand effect on Cu(OTf)2-catalyzed reactions between cyclic vinyloxiranes and dialkylzinc reagents was noted by Feringa et al. [51]. The 2,2 -binaphthyl phosphorus amidite ligands 32 and 43 (Fig. 8.5), which have been successfully used in copper-catalyzed enantioselective conjugate additions to enones [37], allowed kinetic resolution of racemic cyclic vinyloxiranes (Scheme 8.26). 

However, very few catalyst systems reported to date are highly effective for both p- aryl and p-alkyl acyclic enone substrates in the copper-catalyzed asymmetric 1,4-addition. Ligand 27, developed by Hoveyda, shows high enantioselectivity in the 1,4-addition of dialkylzinc reagents to various acyclic enones (Figure 3.6). " ... 

Enantioselective copper phosphoramidite-catalyzed conjugate addition of dialkylzinc reagents to several 4,4-disubstituted cyclohexadienones is achieved with diastereomeric ratios ranging from 1/1 to 99/1 with 85% to 99% ee. When the two substituents are equal (eq 2), selective Re versus Si face-selective addition of the zinc reagent affords a single isomer. Sequential catalytic 1,4-addition to the prochiral dienones gave cis or trans bis-adducts with high enantio and diastereoselectivity. ... 

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. ... 

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. 

Feringa and co-workers developed an efficient methodology for conjugate addition of dialkylzinc reagents to enones catalyzed by copper(II) and the remarkably versatile chiral monophosphoramidite ligand 27 (Scheme 12.6) [18]. 

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