Hiroaki Sasai Ph.D.
||Department / Business Unit
||Department of Synthetic and Organic Chemistry
||State / Provence
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.
Stereoselective Reactions with Planar-Chiral Cyclopentadienyl Complexes
The reaction of planar-chiral cyclopentadienyl-ruthenium complexes with t-butyl isocyanide resulted in the diastereoselective formation of isocyanide complexes under kinetic control (up to >99%de). The reaction with phenyl acetylene followed by the treatment with alumina gave acetylide complexes diastereoselectively (up to >99%de). The planar-chiral cyclopentadienyl-ruthenium complexes served as effective catalysts for the kinetic resolution of racemic allyl carbonates in asymmetric allylic alkylation.
Precise Polymerization with Transition-Metal Complexes
Polymerization of aryl isocyanides possessing chiral ester groups with NiCl2 at room temperature produced helical polymers, of which helical sense selectivity was not so high. Heating of the polymer solution resulted in the increase in the helical sense selectivity. 13C NMR studies suggested that the isomerization around the C=N bonds at higher temperature led to the increase in the stereoregularity of the main chain, which was the origin of the helical structural change.
Efficient Solvent-free Catalytic Oxidation System Using Green Solid Disperse Phase
The search for environmentally benign alternatives to the conventional reaction process using organic solvents has been of great significance in green chemistry. We have developed a new approach to solvent-free catalytic oxidation system using ﾔgreen solid disperse phaseﾕ. We have developed an efficient catalytic solid-phase system for epoxidations that uses cetylpyridinium dodecatungstate ((CetylPy)10[H2W12O42]) catalyst/fluorapatite (FAp) disperse phase with a solid urea-hydrogen peroxide complex (urea-H2O2). The system was reusable and retained its high catalytic activity, although the catalyst was not fixed on the solid-phase. The high efficiency in the solid system is considered to be due to a new non-degraded peroxo species that retains the framework of the parent cluster.
Molecular oxygen as well as hydrogen peroxide is an environmentally benign and low waste oxidant. We developed a solid-phase-oxidation-system using FAp disperse phase and Keggin vanadomolybdophosphoric acid (H3+nPVnMo12-nO40:PVn) with molecular oxygen as a new green catalytic reaction system. The system was efficiently and repeatedly used for solvent-free oxidative dehydrogenation of a-terpinene to p-cymene under mild conditions with 1 atm of molecular oxygen.