Catalytic asymmetric addition of beta-keto phosphonates to an activated imine--formation of optically active functionalized phosphonate alpha-amino acid derivatives.
The direct stereoselective addition of an activated imine to beta-keto phosphonates in the presence of chiral Lewis acid complexes is developed. The evaluation of different activated imines shows that an N-tosyl-alpha-imino ester adds in a diastereo- and enantioselective fashion to beta-keto phosphonates activated by especially chiral copper(II)-bisoxazoline complexes. An evaluation of Lewis acids, chiral ligands and reaction conditions, such as solvent, bases and other additives, shows that high yields, moderate diastereoselectivity and good enantioselectivity are obtained. The scope of the reaction is demonstrated for the reaction of beta-keto phosphonates and finally, the mechanism for the catalytic stereoselective step is presented.
Kjaersgaard
Anne
A
Danish National Research Foundation: Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000, Aarhus C, Denmark.
Jørgensen
Karl Anker
KA
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D007651:Keto Acids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D007097:Imines; D007651:Keto Acids; D063065:Organophosphonates; D012997:Solvents; D003300:Copper