Cuprates, in conjugate addition

The lower-order silyl cuprates are apparently less reactive than the higher-order cuprates in conjugate addition reactions. Reagent (1) has been added in an addition-elimination sequence to an alkylidenemalonate system as a route to vinylsilanes (eq 4). ... 

In summary, the lower-order cyanotrialkylsilylcuprates (1) and (3) react as do most carbon-based cuprates in conjugate additions and carbocupration processes. These reagents are less basic than higher-order cyanocuprates, and less reactive with some less electrophilic partners. 

Experimental evidence indicates that cuprates in solution exist largely as dimer (RiCuLi) (25), which is found as the reactive species in conjugate addition. The kinetic results were consistent with the participation of the dimer (R2CuLi)2/enone complex 26 (Figure 24) in the C—C bond-forming process of the conjugate addition. Relatively unreactive a, -unsaturated ketones, esters and nitriles were also found to form complexes represented by 26 in Figure 24. 

ArSCu(RMgX)n. These heterocuprates are more useful than lithium dialkyl-cuprates for conjugate addition to enones.5 They are also useful for conjugate addition to the less reactive cinnamates and crotonates.6 Yields are markedly improved by use of 2-methoxyphenylthio as the ligand in additions to the crotonates. 

Phosphine-complexed cuprates, formed from copper(I) iodide, 1 mol equiv. of RtLi, and 2-5 mol equiv. of tri-n-butylphosphine, show good reactivity in conjugate addition reactions with enones (Table l).39 The hazards surrounding the use of excess Bun3P, and the availability of other methodologies lower the popularity of this method, but efficiency can be realized with this methodology. 

These mixed cuprates undergo conjugate addition to mono-, di-, and trisubstituted enones in good to excellent yield. Additives such as S(CH3)2 and R3P, which are sometimes necessary in Michael additions of R2CuLi, are not necessary.9... 

The copper-catalyzed 1,4-addition of Grignard reagents to enones has been described by Kharasch in 1941, that is, one decade before the discovery of Gilman cuprates (1952) and more than two decades before the first use of organocuprates in conjugate addition reactions. Consequently, numerous variations and applications of the method have been reported over the years.3 5,7 7a 23 Not surprisingly, several of the advances made in the last decade with... 

Asymmetric -methylation of a, -enones. Chiral bidendate ligands derived from L-prolinol can be used for asymmetric Michael additions to a, 3-enones with cuprates of the type CH,L CuMgBr (10, 266). The highest optical yield in conjugate addition to chalcone is observed when L is (S)-N-methylprolinol (88% ee). The tridentate chiral ligand 1 is equally effective for asymmetric 3-methylation of chalcone with CH,L CuLi and CuBr the chemical yield is 95%. Reduction of the amide carbonyl group of 1 results in practically total loss of chiral induction. 

These results can be explained in terms of an interplay of stereoelcctronic and steric factors. Steric factors are evidently more important in the reaction of bulky cuprate clusters than in the Sakurai reaction. Thus stereoelcctronic factors predominate in the allylsilanc reaction. Similar effects are observed in conjugate additions to substituted cycloheptcn-ones. 

Scheme 6.7. Di a stereo selectivity in conjugate addition of orga no cuprates to chiral cyclic enones of medium ring size.

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