Reaction of homoorganocoppers using external chiral ligands

5 Reaction of homoorganocoppers using external chiral ligands 

Generally, a homoorganocopper reagent has two different metals in the cluster. Their chiral modification needs a chiral ligand whose heteroatoms coordinate selectively to copper and other metals. The first approach along this line was reported by Kretchmer, who used chiral natural diamine 7 as a ligand for methyl-copper in the reaction with cyclohexenone to afford the adduct in only 6% ee [49]. 

The breakthrough in the stoichiometric reaction was brought about by Leyen-decker in 1983 by using hydroxyprolinol-derived sulfide 20 bearing three coordinating sites, as shown in 21 [50]. The reaction of dimethylcopper lithium with chalcone gave the product in 94% ee (Eq. (12.24)). In 1991, Alexakis introduced chiral phosphines, e.g. 22, as the ligands in the reaction of the medium order cuprate with cycloalkenones in the presence of lithium bromide to afford the product in 76-95% ee (Eq. (12.25)) [51]. 

Based on the metal-differentiating coordination concept, proline-derived biden-tate amidophosphines 23-25 were developed. The carbonyl oxygen and phosphorus atoms of the ligand selectively coordinate to lithium and copper atoms of an organocopper species, which discriminate the reaction face of the complex as shown in 26. The reaction of dimethylcopper lithium with chalcone gave the adduct in 84% ee [52]. Enantioselectivity was later improved to 90% with the more bulky amidophosphine 25 based on the model 26 (Eq. (12.26)) [53]. 

Catalytic asymmetric reaction was realized by using 8 mol% of copper iodide and 32 mol% of the chiral amidophosphine 24 to afford the /(-substituted cycloalkanones 

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