In order to construct complex and diverse molecular architectures, it is important to discover and develop powerful reactions that enable the performance of difficult transformations by conventional methods such as Grignard and Wittig reactions. To this end, Prof. Kazuhiko Takai has developed many useful and easily-handled synthetic reactions by generating novel organometallic species of group 4-7 metals such as titanium, chromium, tantalum, manganese, and rhenium based on original concepts. The following is a brief summary of his achievements.
1. Development of Novel Organotitanium and -Chromium Reagents for the Wittig-type Olefination: Although Wittig reagents are useful for the conversion of carbonyl compounds to alkenes, it is still difficult to convert esters (R1COOR2) to the corresponding vinyl ethers [R1C(OR2)=CHR3] and aldehydes (R1CHO) to the corresponding (E)-alkenes (R1CH=CHR2, R2 = alkyl, halides, SiR3, and Bpin) stereoselectively. For the first transformation, Takai developed a novel organotitanium reagent derived from 1,1-dihaloalkanes (R3CHBr2), zinc (with a catalytic amount of lead), titanium(IV) chloride, and TMEDA. The reagent gives (Z)-vinyl ethers from esters in a stereoselective manner. To accomplish the second transformation, Takai developed geminal dichromium reagents by reduction of geminal dihalogen compounds (R2CHX2, R2 = alkyl, halides, SiMe3, and Bpin) with chromium(II) chloride. Because the transformation can be performed under mild conditions, the reagents are widely used for the synthesis of complex molecules especially as components of cross-coupling reactions. This chromium-mediated reaction has become a standard method to construct (E)-olefins from aldehydes, and is generally referred to as the "Takai reaction".
2. Preparation of Tantalum-Alkyne Complexes and their Application to Synthesis: A variety of tantalum-alkyne complexes are easily generated by treatment of alkynes with low-valent tantalum derived from tantalum(V) chloride and zinc. Takai showed that the tantalum-alkyne complexes act as cis-vicinal alkene dianion equivalents and are useful as synthetic intermediates for stereoselective construction of tri- and tetrasubstituted alkenes. The structures of the tantalum-alkyne complexes have also been determined by X-ray crystallographic analysis.
3. Generation of Various Organochromium Reagents for Selective Construction of Carbon Skeletons: Functionalized allylchromium compounds and propargyl-, alkenyl- aryl-, and alkynylchromium compounds are prepared by reduction of the corresponding halides with chromium(II), and the latter three compounds require the addition of a catalytic amount of a nickel salt. The reaction with alkenylchromium reagents under nickel catalysis is often referred to as the "Nozaki-Hiyama-Kishi reaction". The nucleophilic addition of these organochromium reagents to carbonyl compounds, usually to aldehydes, proceeds under mild conditions in a chemo- and stereoselective manner even in the presence of many oxygen-containing functionalities. Therefore, this method has been used in many total syntheses, especially those of marine natural products such as palytoxin, brevetoxin B, and halichondrin B. Takai has written a review in Organic Reactions on nucleophilic addition of organochromium reagents.
4. Discovery of Effects on the Reducing Ability of Mother Metals by Secondary Metal Elements: Zinc powder derived from the pyrometallurgy smelting method (distillation) contains a trace amount of lead. In contrast, zinc from hydrometallurgy (electrolysis) is pure and free from lead. Takai has clarified that the capricious reactivity of zinc in the Simmons-Smith reaction and preparation of alkylzinc compounds from iodo alkanes heavily depends on a trace amount of lead. This discovery and the effects of a catalytic amount of nickel for the generation of alkenylchromium reagents were warnings that contamination by a trace amount of secondary metal elements can occur when using inorganic metals (or salts). He also showed how to activate several metals such as zinc, manganese, and aluminum by addition of secondary metal elements.
5. Control of One-Electron Transfer and its Application to Sequential Radical and Anionic Reactions: Radicals are usually generated by homolytic cleavage of single bonds. They can also be prepared by one-electron reduction of alkyl halides or unsaturated compounds. Takai revealed that manganese metal can be activated by treatment with a catalytic amount of lead(II) chloride and Me3SiCl, and that the activated manganese metal can be utilized effectively for stepwise one-electron reduction of alkyl iodides. Three-component coupling reactions of alkyl iodides, electron-deficient olefins, and carbonyl compounds can be accomplished with activated manganese based on the concept of sequential generation of radical and anionic species. Such sequential one-electron reduction was also applied to the sequential aldol reaction-cyclopropanol formation using chromium(II) as a reductant.
6. Development of Novel Rhenium- and Manganese-Carbonyl Catalyzed Reactions: In contrast to late-transition metals such as palladium, rhodium, and ruthenium, rhenium complexes have not been popular as catalysts for organic synthesis except in a few cases such as catalytic reactions with rhenium-oxo complexes or MeReO3. Therefore, the reactivity of rhenium complexes has not been explored as extensively as that of other transition metal complexes. Takai focused on rhenium-carbonyl complexes and discovered their novel catalytic activity, namely, C-H bond activation, C-C single-bond cleavage, and novel cycloaddition reactions. In addition, he found that carbonyl complexes of manganese, also a group 7 metal, have similar reactivity to the rhenium complexes. In contrast to conventional C-C bond formation which usually employs organic halides as starting materials, thus producing metal halides as byproducts, this process does not produce undesirable waste, and is environmentally benign. By using this process, new organic functional materials have also been produced.
In summary, Prof. Kazuhiko Takai has created various novel and useful synthetic reagents for organic synthesis from a deep insight into the features of group 4-7 metal elements, and has developed useful transformations that are difficult to achieve by conventional methods. He has opened new vistas in the field of synthetic organic and organometallic chemistry, and has had (and will continue to have) great influence on the synthesis of natural products and functional materials. His contribution is highly valued worldwide, and he therefore deserves The Chemical Society of Japan Award.