New Approach to Biomimetic Transamination Using Bifunctional 1,3-Proton Transfer Catalysis in Thioxanthenyl Dioxide Imines

A pyridoxamine equivalent, 9-aminothioxanthene 10,10-dioxide, has been designed that is capable of affording transamination in good to excellent yields of natural as well as artificial amino acids. Amidines and guanidines in catalytic amounts were capable of performing 1,3-proton transfer in the imines under mild conditions, whereas various simple amines failed. The use of chiral catalysts resulted in modest asymmetric induction (ee < or = 45%). The electronic dependence in para-substituted phenyl glyoxylate imines, isotope effects, and computational studies support a stepwise, bifunctional mechanism for amidine and guanidine catalysts. Attempts toward an autocatalytic model system are described.