During his research career, Dr. Kambe, Professor of Chemistry at Osaka university, has discovered various synthetic reactions that involve the use of heavy heteroatom compounds and transition metal complexes combined with the use of organometallic compounds. His major achievements are based on the formation of highly coordinated hypervalent heteroatom compounds and transition metalate complexes and their applications to organic synthesis.
1. Formation of Hypervalent Heteroatom Compounds and Their Applications in Organic Synthesis
Typical elements obey the octet rule and form organic compounds with the eight outermost electrons in their valence orbitals forming covalent bonds with other atoms. For example, ethers, on reaction with organometallic compounds such as organolithium compounds or Grignard reagents, coordinate to the metals by donating a lone pair of electrons as a Lewis base. On the other hand, tellurides, an ether analogue, react with such organometallic compounds as a Lewis acid by accepting the lone pair of electrons of carbanions into a C-Te antibonding σ* orbital, thus forming an anionic tellurium complex carrying three substituents with a three-center-four-electron hypervalent bond. These metal tellurolates undergo ligand elimination in equilibria to generate more themodynamically stable carbanions. This SN2 reaction at tellurium was found to be extremely rapid, even at low temperatures, much faster than the corresponding Sn-Li exchange that has been widely employed for generating a variety of organolithium compounds. The synthetic utility of this exchange reaction was demonstrated by the efficient generation of carbonyllithium compounds and their successful trapping with various electrophiles. These carbonyllithiums are umpolung species which are extremely kinetically unstable. By using this Te-Li exchange technique, a variety of organometallic species containing alkali metals and alkali earth metals were generated and employed in organic synthesis.
Kambe extended this strategy based on hypervalent intermediates to radical chemistry. He revealed that radical substitution reactions (SH2) also took place efficiently on chalcogen atoms and that tellurides react with carbon radicals faster than the corresponding iodides by more than one-order of magnitude to participate in SH2 reactions. A variety of transformations that involve inter- and intramolecular radical reactions were developed in which C-Te bonds were cleaved and added across unsaturated bonds. Other heteroatom compounds including selenium and sulfur were also synthesized and employed as useful intermediates in organic synthesis.
2. Development of Synthetic Reactions Using Transition Metal Anionic Complexes as Key Intermediates
The successful results described above prompted him to study anionic transition metal complexes with the goal of developing new synthetic reactions. He generated ate complexes of Ti, Zr, Co, Rh, Ni, Pd, Cu and examined their reactivities. With a working hypothesis stating that π-carbon ligands such as allyl groups or alkynes stabilize anionic complexes by withdrawing electrons from the central metal by back donation, he was able to generate a variety of ate complexes using Grignard reagents in the presence of butadienes or alkynes. One of the exciting outcomes of his research was the transition metal catalyzed cross-coupling reaction between sp3-carbon centers. Nickel, as well as palladium, was found to catalyze the cross-coupling of alkyl (pseudo)halides with alkyl Grignard reagents under mild conditions in the presence of butadiene. This reaction proceeds efficiently without the need for heteroatom ligands such as amines or phosphine derivatives, which were commonly employed in transition metal catalyzed reactions, thus demonstrating the potential of such a reaction in large scale synthesis. The reaction proceeds rapidly via all 16-electron intermediates, making the present reaction compatible for use in conjunction with a wide variety of functional groups including esters, ketones, nitryls etc. Very high turn-over numbers of up to ten to the sixth order were attained in copper catalyzed alkyl-alkyl cross-coupling when butadiene or alkynes were used as ligands, permitting the use of tert-alkyl Grignrad reagents to construct quaternary carbon centers and the use of less reactive alkyl chlorides or fluorides as cross-coupling partners between unactivated sp3-carbons centers. Kambe also developed convenient methods for introducing alkyl and/or silyl groups to olefins and dienes using titanium as well as zirconium as catalysts via the combined use of alkyl halides and/or chlorosilanes in the presence of Grignard reagents. The alkylation and/or silylation of conjugated dienes with or without their dimerization was also achieved using nickel and palladium catalysts.
It was also revealed that electron rich anionic complexes serve as good electron transfer reagents. Kambe developed efficient methods for generating various carbon radicals from alkyl halides by reactions with in situ formed metalate complexes and developed useful procedures for the construction of carbon skeletons by means of a combination of transition metal catalyzed processes and free radical processes.
In summary, Professor Kambe's efforts have resulted in the development of a new field of heteroatom chemistry based on the unique properties of heavy heteroatom elements to form highly coordinated structures and developed various novel synthetic transformations utilizing SN2 and SH2 reactions as key processes to produce carbanions and carbon radicals. He applied this principle to transition metals and developed unique catalytic reactions in which anionic ate complexes play important roles. His outstanding achievement includes the successful development of efficient bond forming reactions between sp3-carbons catalyzed by transition metals, leading to significant contributions to expanding the scope of cross-coupling to saturated hydrocarbon chemistry. Accordingly, it was approved that his achievements are clearly deserving of his receiving Chemical Society of Japan (CSJ) Award.