The First Catalytic Enantioselective Aldol-Type Reaction of Ethyl Diazoacetate to Ketones

The aldol-type addition to ketones still represents a great challenge in asymmetric catalysis. Recently, the direct aldol reaction between the commercially available ethyl diazoacetate and aldehydes has attracted increasing attention. Ethyl diazoacetate is economical and allows further transformation of the aldol adduct obtained. We present a solution for the arduous, and not previously described, addition of diazoacetate to ketones. Our procedure employs commercially available norephedrine-derived ligands and dialkylzinc reagents [R2Zn: (diethylzinc, Et2Zn; dimethylzinc, Me2Zn)] as starting materials, therefore the active catalyst is prepared with a very straightforward methodology. Remarkably, the reaction gives good enantiomeric excesses with alpha-halo ketones, a class of compounds that has not been commonly used in enolate addition.