Catalysts are the most important substances for efficiently controlling the reactivity and selectivity of organic reactions. Although enzymes control a huge number of reactions in living systems with extremely high substrate-, chemo-, regio-, site- and stereoselectivity, their substrate scopes and applicable conditions are quite limited. In addition, there are only half a dozen types of enzymatic reactions: (1) oxidation and reduction, (2) group transfer reaction, (3) formation or removal of a double bond with group transfer, (4) hydrolysis, (5) isomerization of functional groups, and (6) formation of a single bond through eliminating of the elements of water. Dr. Kazuaki Ishihara established a rational methodology for designing high-performance unimolecular or supramolecular catalysts based on the chemistry of acid?base combined catalysis for numerous types of organic reactions. The rational design of catalysts using non-covalent bonding interactions such hydrogen bonding, halogen bonding, π-cation, n-cation, π-π, hydrophobic, hydrophilic, fluorophilic interactions, etc., is useful for controlling their catalytic activities and selectivities. He classified acid-base combined catalysts into two types: ion pair-type (A) and amphoteric molecule-type (B). Furthermore, type A can be subclassified into acidic ion pair-type (A1), neutral ion pair-type (A2), and basic ion pair-type (A3). On the other hand, type B can be subclassified into conjugationally non-interactive-type (B1) and conjugationally interactive-type (B2). He developed various high-performance catalysts based on acid-base combination chemistry. Representative catalysts that he developed are summarized as follows.
Design of Acidic Ion Pair Catalysts (A1). He developed sterically bulky N,N-diarylammonium pentafluorobenzenesulfonates, which are effective as reverse micelle-type catalysts for the dehydrative condensation reaction between carboxylic acids and alcohols in hydrophobic solvents. Catalytic esterification proceeds quantitatively without removal of the water produced. Furthermore he developed chiral primary ammonium salts, which are effective for the enantioselective [4+2] and [2+2] cycloaddition reactions of 2-acyloxyacroleins, and ammonium or alkali metal salts derived from chiral 1,1'-binaphthyl-2,2'-disulfonic acids, which are effective for the enantioselective addition reactions of several carbon nucleophiles to aldimines. Thus, he demonstrated the in situ preparation of high-performance supramolecular catalysts from appropriate acidic and basic components. Moreover, he established a method for activating acidic reagents with catalytic bases as active ion pairs. The first successful example was the enantioselective biomimetic iodocyclization of linear polyprenoids using a chiral iodonium complex that is generated in situ from N-iodosuccinimide with chiral phosphoramidite. Furthermore, he developed a dual activation system consisting of molecular iodine with chiral phosphates and N-halosuccinimide for catalytic enantioselective iodolactonization. In this catalytic system, a halogen-bonding interaction between molecular iodine and N-halosuccinimide realizes the in situ generation of an extremely active chiral iodonium salt species with weak Lewis bases such as chiral phosphates.
Design of Neutral Ion Pair Catalysts (A2). He developed chiral quaternary ammonium iodides, which are effective as precatalysts for the enantioselective oxidative cyclization reaction of (2-hydoxyphenyl)ketones to produce optically active 2-acyl-2,3-dihydrobenzofurans and 2-acylchromans in the presence of hydrogen peroxide or alkyl hydroperoxides as oxidants. The in situ-generated ammonium hypoiodites are the actual catalytic species. In these reactions, only water or alcohol is generated as a byproduct. Optically active α-tocophenol was concisely synthesized by using this catalytic reaction as a key step. He also developed novel zwitterion salts of aryl isothiocyanates with 4-pyrrolidinopyridine, which are effective as organocatalysts for the transesterification reaction.
Design of Basic Ion Pair Catalysts (A3). He developed a zinc chloride-catalyzed alkyl addition of Grignard reagents to aldehydes and ketones to produce secondary and tertiary alcohols. In this reaction, trialkylzinc ate complexes are generated in situ, and catalytically promote selective alkyl addition. Trialkylzinc ate complexes are more nucleophilic than Grignard reagents but less basic than alkyllithium reagents. He also developed chiral lithium phenoxides derived from BINOL for an enantioselective trimethylsilylcyanation to aldehydes and ketones and an enantioselective Mannich-type reaction of 1,3-dicarbonyl compounds to aldimines. The nucleophilicity of the trimethylsilyl cyanide and 1,3-dicarbonylcompounds is increased by the anions of the catalysts.
Design of Conjugationally Non-interactive Catalysts (B1). He developed an L-histidine-derived sulfonamide catalyst for use in asymmetric esterification. Hydrogen bonding interaction between the substrate and catalyst plays an important role in asymmetric induction. Furthermore, he developed a copper(II) complex with chiral bisoxazoline bearing sulfonamide moieties for enantioselective [4+2] and [3+2] cycloaddition reactions. The sulfonamido moieties of the ligand play an important role in increasing the Lewis acidity of the copper(II) and constructing a chiral cavity around the copper(II) center through n-copper(II) and hydrogen bonding interactions. He developed hypervalent organoiodine(III) catalysts bearing carboxamide moieties for the enantioselective dearomatization. The acidic protons in these catalysts promote high enantioselectivity through hydrogen-bonding interactions.
Design of Conjugationally Interactive Catalysts (B2). He developed a 2-iodoxybenzenesulfnoic acid (IBS)-catalyzed oxidation of alcohols with oxones. IBS was prepared in situ from 2-iodobenzenesulfonic acid and oxones. Iodine(V) and the oxygen of I=O in IBS respectively act as an acid and base conjugationally. IBS-catalyzed selective oxidation of primary alcohols, secondary alcohols, ketones, and phenols gives the corresponding aldehydes, ketones, esters, and ortho-quinones. Molybdenum(VI) oxides are highly effective as conjugationally interactive catalysts for the dehydrative condensation of N-(2-hydroxyethyl)carboxamides and N-(2-mercaptoethyl)carboxamides to oxazolines and thiazolines, respectively. Similarly, oxorhenium(VII) complexes are highly effective as catalysts for the direct condensation of phosphoric acid with alcohols to give the corresponding acid monoesters selectively. Zinc(II) complexes with chiral P,P-diaryl-N-(2-(pyrrolidin-1-yl)ethyl)phosphinic amides are highly effective catalysts for the enantioselective addition of organozincs to aldehydes and ketones. More recently, he developed tailor-made chiral supramolecular catalysts for the endo/exo- and enantioselective Diels-Alder reaction through the complexation of conjugationally interactive chiral boronates and sterically bulky tris(pentafluorophenyl)borane. A chiral deep and narrow cavity of the supramolecular catalysts induces high endo- and enantioselectivities, while a chiral shallow and wide cavity of the catalysts induces high exo- and enantioselectivities.
These achievements have led to the development of high-performance catalysts, which have been shown to have remarkable levels of catalytic activity and selectivity under environmentally-benign conditions. In industry, this rational approach to the design of high-performance catalysts based on the chemistry of acid-base combined catalysis significantly contributes to the discovery of new drugs and functional organic materials and the development of low-cost processes for their manufacture. His contributions have been recognized worldwide, and he is eminently deserving of being the recipient of The Chemical Society of Japan Award.