The first catalytic highly enantioselective alkylation of ketimines--a novel approach to optically active quaternary alpha-amino acids.
A series of novel ketimines with intrinsic protecting group anchoring was synthesized and allowed to react with various silylketene acetals in the presence of 5-10 mol % of a chiral Zn(OTf)(2)-(R,R)-Ph-pybox-aqua complex. The corresponding optically active quaternary alpha-amino acid derivatives were obtained in high yields and with enantioselectivities ranging from 34 % up to 95 % ee. The catalyst was studied by (1)H NMR spectroscopy and X-ray crystallography, and a dynamic equilibrium of two species was identified in solution. These are a homo-chiral 1:2 metal-ligand complex and a 1:1 metal-ligand complex, of which the latter is expected to be the actual catalyst of the diastereo- and enantioselective reaction. A strong positive nonlinear effect was observed due to the formation of a catalytically inactive 1:2 metal-ligand hetero-chiral complex. On the basis of DFT calculations and the absolute stereochemistry of the products, simultaneous coordination of the imino electrophile and a single molecule of H(2)O to the chiral Lewis acid complex is proposed. Coordination of the imine-nitrogen atom in the axial position of an octahedral complex can account for the facial selectivity as well as the diastereoselectivity observed.
Saaby
Steen
S
The Danish National Research Foundation: Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
Nakama
Kimitaka
K
Lie
Mette Alstrup
MA
Hazell
Rita G
RG
Jørgensen
Karl Anker
KA
D000080:Acetals / Q000737:chemistry; D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D005030:Ethylenes / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D008024:Ligands; D008670:Metals / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
D000080:Acetals; D000596:Amino Acids; D005030:Ethylenes; D007097:Imines; D007659:Ketones; D008024:Ligands; D008670:Metals; D009942:Organometallic Compounds; D015032:Zinc; C008223:ketene