Design of a small-molecule catalyst using intramolecular cation-π interactions for enantioselective Diels-Alder and Mukaiyama-Michael reactions:: L-DOPA-derived monopeptide-Cu(II) complex

We have designed a small-molecule artificial metalloenzyme that is prepared in situ from Cu(OTf)(2) or Cu(NTf2)(2) (1.0 equiv) and L-DOPA-derived monopepticle (1.1 equiv). This catalyst (2-10 mol %) is highly effective for the enantioselective Diels-Alder (DA) and Mukaiyama-Michael (MM) reactions with (alpha,beta unsaturated 1-acyl-3,5-dimethylpyrazoles. The present results demonstrate that cation-pi interactions may be available for controlling the conformation of sidearms of chiral ligands, and monopeptides are readily tunable ligands that include only one chiral center.