Outlines

Asymmetric synthesis, a phenomenon fine tuned to perfection by nature, forms the central theme of our research efforts. We have been interested in the design and syntheses of a novel class of chiral ligands that are unique in promoting new asymmetric reactions. The mechanisms of these organic reactions are also studied by means of physical organic techniques. Novel chiral spiro ionic liquids and organocatalysts have been synthesized with a focus on developing environmentally benign asymmetric processes.

Current Research Programs

Development Multifunctional Asymmetric Catalysts
Multifunctional asymmetric catalysts such as La-Li3-tris(binaphthoxide) (LLB) complex and Al-Li-bis(binaphthoxide) complex (ALB) function like an enzyme by activating two different substrates to facilitate a chemical reaction. In a similar manner, a homo-dinuclear catalyst should be able to activate two identical substrates in a homolytic coupling reaction. Chiral dinuclear vanadium(IV) complexes with axial skeletons have been synthesized and found to promote the enantioselective oxidative coupling of 2-naphthol derivatives through a dual activation mechanism affording the product with up to 94% ee. The dual activation mechanism in this system was supported by the kinetic analysis and catalyst loading effects.
A new double-activation catalysis for the Morita-Baylis-Hillman (MBH) reaction of an a,b-unsaturated ketone and an aldehyde has also been established by the combined use of multifunctional asymmetric complexes and tributylphosphine, (n-Bu)3P. The above asymmetric catalyst is found to accelerate the enantioselective MBH reaction to afford the adduct in good chemical yield with up to 99% ee.

New Asymmetric Spiro-type Ligands
So far we have developed a new type of chiral bis(isoxazoline) ligand with spiro[4.4]nonane skeleton (SPRIXs). Pd(II)-SPRIXs catalyst is quite effective to promote highly enantioselective reactions such as tandem cyclization of dialkenylalcohols with up to 95% ee. For the improvement of SPRIX, novel spiro-type ligands which contain both isoxazole and isoxazoline ring were designed. Among the synthesized ligands, the hybrid ligand bearing isoxazole and isoxazoline ring with spiro[5.4]decane skeleton showed great affinity towards Pd(II) salts and the resulting chiral Pd(II)-hybrid ligand complex mediated the catalytic asymmetric tandem cyclization of dialkenylalcohols in higher yield with comparable enantioselectivity. The lack of acceleration effects with oxazoline ligands clearly shows the crucial role of isoxazolines/isoxazoles in the above reactions.

Chiral Ionic Liquids and Organocatalysts
Ionic liquids have proved to be good alternatives for conventional solvents as they offer recyclable and greener reaction media. Spiro imidazolium salts, spiro pyridinium salts and spiro ammonium salts have been designed and synthesized for use as chiral ionic liquids and chiral phase transfer catalysts respectively.
The aza-MBH reaction is a C-C bond-forming reaction of activated alkenes with imines catalyzed by Lewis bases, such as amines or phosphines, to give highly functionalized allylic amines. Two types of chiral bifunctional organocatalysts for enantioselective aza-MBH reaction of a,b-unsaturated carbonyl compounds with N-tosylimines, which possess Brｿnsted acid unit and Lewis base unit, have also been developed. The enantioselective reactions promoted by the chiral organocatalysts proved to be deeply influenced by the position of the Lewis base unit on the BINOL skeleton. Especially, in the (S)-3-(N-isopropyl-N-3-pyridinylaminomethyl)BINOL catalyzed aza-MBH reaction, the acid-base functionalities are required for not only the activation of the substrate but fixing the conformation of the organocatalyst.

Highly Effective Synthesis of Functionalized Nano Particles
Spherical particle such as a dendrimer has attracted much attention due to the great potential of applications in material science.
Taking advantage of the facile adsorption of thiols to the surface of gold cluster, the disulfide bearing (R)-BINOL moieties at each terminal position has been successfully introduced on monolayer-protected metal cluster (MPC). Treatment of the metal cluster with Ti(O-i-Pr)4 afforded an insoluble Ti-BINOLate complex with high catalyst activity in the asymmetric alkylation of aldehyde with dialkylzinc. As an alternate approach, dendrimer-like catalyst was synthesized by immobilization of (R)-BINOL derivative on the polymer obtained by micellar polymerization system. The polymer-supported Ti-BINOLate complex generated with this polymer also exhibited high catalytic activity. Further applications of functional particles to new asymmetric reactions are in progress.