Enantioselective mannich-type reactions using a novel chiral zirconium catalyst for the synthesis of optically active beta-amino acid derivatives

Catalytic enantioselective Mannich-type reactions of silyl enol ethers with aldimines have been successfully performed using a novel chiral zirconium catalyst prepared from zirconium(IV) tert-butoxide (Zr((OBu)-Bu-t)(4)), 2 e quiv of (R)-6,6'-dibromo-1,1'-bi-2-naphthol ((R)-6,6'-Br2BINOL), and N-meth ylimidazole. The use of aldimines having N-substituted hydroxyphenyl moieti es is essential for obtaining high selectivities, and the N-substituted gro ups were converted to free amines using oxidative cleavage. Aldimines deriv ed from aromatic aldehydes as well as heterocyclic and aliphatic aldehydes reacted with silyl enol ethers smoothly to afford the corresponding beta-am ino acid derivatives in high yields and high enantioselectivities. Several NMR experiments have been conducted to clarify the structure of the chiral Zr catalyst and also the catalytic cycle of this asymmetric reaction. Final ly, a new BINOL derivative. (R)-6,6'-bis(trifluoromethyl)-1,1'-bi-2-naphtho l ((R)-6,6'-(CF3)(2)BINOL), has been prepared. It was shown that the turnov er of the catalyst using this novel ligand was improved, and high levels of yields and selectivities were obtained in the presence of a small amount o f the zirconium catalyst.