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Design of Sophisticated Acid Base Catalysts and the Application to Organic Synthesis
Apart from enzymes as biocatalysts, a broad repertoire of chiral reagents, auxiliaries, and catalysts can be developed in recent years. In this respect, the design of new catalysts and new reactions in an environmentally benign manner is increasingly important in the 21st century for the construction of new and useful molecules. Accordingly, professor Maruoka has investigated the design of highly sophisticated, chiral acid/base catalysts in order to achieve the hitherto unattainable reactivity and | |
Prof. Keiji Maruoka
Kyoto University (School of Science)
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selectivity in various organic transformations. Described below are my major research achievements.
1. Chemistry of Designer Lewis Acids
A conceptually new molecular recognition chemistry has been developed by using the coordination bonding between certain metals and heteroatoms in substrates. In particular, a new Lewis acid possessing an appropriate coordination site for an alkyllithium nucleophile has been designed as a two-point binding reagent for a conceptually new amphiphilic conjugate alkylation, thereby allowing the hitherto difficult conjugate addition of reactive nucleophiles to α,β-unsaturated aldehydes. Such a reaction system mimics the biological enzyme/coenzyme/substrate combination.
2. Chemistry of Bidentate Lewis Acid Catalysts
Electrophilic activation of carbonyl groups with certain Lewis acids is a well-established method for enhancing their reactivity and selectivity toward nucleophilic addition. Here, simultaneous coordination to carbonyl groups with two metals would dramatically alter the reactivity and selectivity of the carbonyl substrates. Examples of such double coordination with two main-group metals are rare despite its potential importance, simply because of the high preference for the single coordination mode even in the presence of excess Lewis acids, and hence the nature of such di-?-bonding remains an elusive phenomenon. In this context, he has been interested in the possibility of designing a bidentate Lewis acid that is capable of preferable di-?-bonding with two metals. Among various metal elements, aluminum and titanium seem to be the metals of choice in view of their high affinity toward oxygen atom. Thus, certain bis-Al and bis-Ti reagents can be designed as bidentate Lewis acids for the double activation of carbonyl and ether substrates. This concept has been further extended by the design of chiral, bidentate Ti Lewis acid catalysts derived from binaphthol and bis-titanium oxide for the precise enantioface discrimination as well as the more effective activation of aldehyde carbonyl. Accordingly, he developed several asymmetric transformations including a new asymmetric allylation of aldehydes and a new asymmetric1,3-dipolar cycloaddition reaction by using a newly designed, chiral bidentate bis-Ti oxide.
3. Chemistry of Chiral Organocatalysts
3-1 Design of Chiral Phase-Transfer Catalysts
@The phase transfer reactions have been recognized as a convenient and highly useful synthetic tool in both academia and industry because of several advantages of phase transfer reactions (i.e., operational simplicity, mild reaction conditions with aqueous media, environmental consciousness, suitability for large-scale reactions, etc.), which meet the current requirement for practical organic synthesis. In addition, these non-metallic organocatalysts make possible to realize the environmentally benign synthetic reaction processes. A series of spiro-type chiral phase transfer catalysts have been devised from commercially available chiral binaphthol, thereby allowing the practical large-scale synthesis of useful compounds, in particular natural-type and unnatural-type amino acids and peptides for the pharmaceutical purpose. This method allows the large-scale synthesis of various artificial amino acids, which are hitherto difficult to obtain by the previous industrial approaches. Various biologically active amino acids such as L-Dopa, L-Azatyrosine, ACE inhibitor, and dihydro- and tetrahydroisoquinoline alkaloids can be readily synthesized. Moreover, the hitherto very difficult, catalytic asymmetric synthesis of α,α-dialkylamino acids can be established by way of sequential double alkylations of glycine derivatives with high enantioselectivity. These chiral catalysts have attracted considerable attention from the industrial world, mainly because about 20% of the top best-selling 500 medicines contain amino acids and their derivatives. The chiral phase transfer catalysts, which are now commercially available as gMaruoka CatalystTMh from Sigma-Aldrich Inc. and Wako Pure Chemical Ind., are also applicable to direct asymmetric aldol synthesis, asymmetric alkylation of β-keto esters, asymmetric nitroaldol synthesis, asymmetric conjugate addition, and terminal functionalization of small peptides. Furthermore, a structurally simplified, highly active chiral phase transfer catalyst with the catalyst loading of 0.01 mol% can be designed, and is commercially available from Kanto Chemical and Strem Co.
3-2 Design of Bifunctional Organocatalysts
@Certain new, bifunctional organocatalysts have been designed which are structurally different from proline catalyst. Accordingly, a binapthyl-modified chiral amino acid catalyst and a chiral aminosulfoneamide catalyst can be prepared as additional bifunctional organocatalysts, and successfully applied to the practical asymmetric aldol reaction and asymmetric Mannich reaction. This concept is aldo applied to the asymmetric hydroxyamination of aldehydes by designing a binapthyl-modified chiral dihydroxyamino catalyst.
4. Chemistry of Hypercoordinated Main Group Elements
He also proposed the possibility of existing chelated five-coordinated boron and aluminum compounds, and demonstrated the existence of such hypercoordinated boron and aluminum compounds in addition to their synthetic applications.
As a whole, professor Maruoka has developed the creative research work based on his original idea in organic chemistry, which has a great impact not only on organic chemistry but also on related fields. Judging from such research achievements as well as his internationally high reputation, he was recognized as a recipient of the Japan Chemical Society Award.
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