Research Area

 

Our aim is to develop new synthetic methodologies based on selective cleavage and applications of C–H, C–C and C–X bonds mediated or catalyzed by organometallic compounds in the hope of finding new-generation material transformations. Six projects are in progress:

1) Co-operative Effect of Lewis Acids with Transition Metals for Organic Synthesis

2) Research and Development of Organo-bi-metallic Reagents

3) Monometallic Reagents --- 1-Lithio-1,3-Butadienes as Useful Building Blocks

4) Selective Cleavage of C–C and C–X Bonds of Inert Ligands Facilitated by External Reagents Attack on Organometallic Compounds

5) Reaction Chemistry and Application of Bis(alkynyl)silanes

6) Isolation and Structural Characterization of Active Organometallic Intermediates

Co-operative Effect of Lewis Acids with Transition Metals for Organic Synthesis

 

Transition metal-mediated or -catalyzed C–C bond or C–X bond forming reactions are among the most powerful tools in organic synthesis Meanwhile, Lewis acid-mediated or -catalyzed organic transformations are widely used. However, an effective combination of these two powerful protocols or effective cooperation of transition metal (TA) and Lewis acid (LA) should open a new era in modern synthetic chemistry. The concept of cooperation effect between transition metal and Lewis acid is summarized as a tutorial review in Chem. Soc. Rev. 2007, 36, 1395. Herein a brief introduction of cooperation effect is shown. Lewis acids may play a very important role in many types of transition metal-mediated chemical bond forming reactions, mainly including (1) promoting reactivity (type I). The M–C bond in this category does not react or reacts very slowly with certain substrates without Lewis acids. However, in the presence of Lewis acids, the reaction proceeds or speeds up. (2) Increasing the selectivity of the reaction (type II), and (3) changing the reaction direction (type III) from Product A (without LA) to Product B (with LA).  

 

The present research project was initiated in 1998. Zirconacyclopentadienes did not react with aldehydes in the absence of Lewis acids. However, a new cycloaddition reaction of two molecules of alkynes with an aldehyde by deoxygenation of the carbonyl bond mediated by AlCl3 and zirconocene was achieved for the first time to give multi-substituted cyclopentadiene derivatives. The reaction proceeded with a formal [2+2+1] pattern. It was the first example of deoxygenation cyclization of the C=O double bonds of carbonyl compounds, and provided a new method for the preparation of cyclopentadienes by one-pot procedure from readily available alkynes and aldehydes. Hereafter, a series of both Lewis acid and zirconocene mediated reactions between unsaturated substrates and aldehydes was developed. For example, the reaction of one alkyne, one alkene and one carbonyl compound yielded homoallylketones and 2, 5-dihydrofurans with a formal [2+2+2] pattern. In the case of isocyanates, selective cleavage of C=N or N=O double bonds was found. Recently, much attention has been directed to organochromium-mediated or -catalyzed C–C or C–X bond forming reactions.

 

 Research and Development of Organo-bi-metallic Reagents 

 

Development of organometallic reagents has been one of the most important areas in synthetic chemistry, since practically useful and efficient reagents can remarkably accelerate the advancement of synthesis and related subjects. We have found and developed a new type of organolithium reagents---1,4-dilithio-1,3-butadienes since 1999, which can exhibit many novel and unprecedented reactivities toward unsaturated substrates, such as CO, CO2, aldehydes, ketones, nitriles and etc. The special type of organolithium reagents is quite different from traditional organolithiums, owing to the cooperative manner between two alkenyllithium moieties. This work has been published as a review in Eur. J. Org. Chem. 2004, 2773. Very recently, a new type of lithio siloles from readily available silyl 1,4-dilithio- 1,3-butadienes via novel reaction mechanisms were prepared, which are more general in terms of substitution patterns and synthetic methods. Then we developed other organo-bi-metallic reagents, such as dimagnesium reagents, dialuminium reagents, diiron reagents, dicopper reagents, and etc. Our results demonstrated that these organo-bi-metallic reagents could exhibit some unexpected reactivities, probably because of cooperative effects between bimetallic moieties and various substrates, which enriched the chemistry of orgao-bi-metallic compounds and offered a variety of highly efficient and useful methods for the preparations of many important intermediates and functional materials, such as octatetraene, cyclooctatetraene, tricyclo [3.3.0.02,8]3,6-octadiene, tricyclo [3.3.0.02,6]3,7-octadiene, and etc.

 

 

 

 Monolithio Reagents---1-Lithio-1,3-Butadienes: Useful Building Blocks for Cyclic Compounds 

 

Besides our continuous investigation on 1,4-dilithio-1,3-butadienes, new reactions and useful applications could be also achieved from the unique structure of monolithio reagents 1-lithio-1,3-butadienes. There are at least three points should be considered for the reactions of monolithio reagents, e.g. (1) the alkenyllithium moiety, (2) the butadienyl skeleton, and (3) the substituent X. Obviously, the alkenyllithium moiety is most likely to react with a variety of organic substrates following the common way of monlithio reagents. However, our recent results have revealed that substituted 1-lithio-1,3-butadienes can serve as building blocks for the preparation of a wide variety of cyclic compounds and linear compounds. The intra-cooperation between the alkenyllithium moiety and the butadienyl skeleton is the essential factor which makes 1-lithio-1,3-butadiene derivatives useful and unique as building blocks. In addition, the substitution patterns and the nature of the substituents on the butadienyl skeleton have been demonstrated to affect remarkably the reaction pathways of 1-lithio-1,3-butadienes. This work as VOL.80 Commemorative Accounts is published in Bull. Chem. Soc. Jpn. 2007, 80, 1021.

 

 

Selective Cleavage of C–C and C–X Bonds of Inert Ligands Facilitated by External Reagents Attack on Organometallic Compounds.

 

Cyclopentadienyl ligands (Cp) are the most popular ligands for stabilization of various metal complexes, including those of early transition metals and lanthanides. It is well-known that a Cp ligand usually acts as an inert ligand toward the C–C bond cleavage on transition-metal complexes since the first preparation of ferrocene in 1951. However, in 2003, as a joint project we and Takahashi et al discovered that two C–C bonds of a Cp of titanacyclopentadienes were cleaved into a two-carbon unit and a three-carbon unit in the presence of two nitriles, which were converted into a benzene derivative and a pyridine derivative, respectively. This is the first example that Cp ligands participate in a reaction fashion under appropriate conditions. This work was highlighted in Angew. Chem. Int. Ed. 2004, 43, 1463.

 

Further, an unusual migration of an alkyl group via C–C bond cleavage of a Cp ligand of titanacyclopentadienes was found to yield indene derivatives as shown below. Novel reactivities of this kind will further change our understanding of the cyclopentadienyl ligand.

 

 

Reaction Chemistry and Application of Bis(alkynyl)silanes

Bis(alkynyl)silane (ArC≡C)2SiMe2 is of significant importance in transition metal-mediated or -catalyzed organic synthesis because of their potential C–Si bond cleavage and applications. Thermodynamically favored six-membered zirconacyclohexadienes were formed in one-pot procedure from the zirconacyclobutene-silacyclobutene complexes, which were generated in-situ by reaction of (ArC≡C)2SiMe2 with 1 equiv of “CpZr(II)”, via this unprecedented alkyne-induced C–C and C–Si bond cleavage process as reported by Takahashi group. Interestingly, a zirconocene-mediated intermolecular coupling reaction of one molecule of (ArC≡C)2SiMe2 with three molecules of organonitriles was found to afford pyrrolo[3,2-c]pyridines via cleavage of one of the three C–N triple bonds and the two Si–C bonds. This work represents a successful example combining the two useful strategies based on the metal-mediated or -catalyzed cleavage of chemical bonds and the one involving multicomponents either added at once or added sequentially, and provides an attractive method for the preparation of N-containing heterocyclic compounds from easily available organonitriles via activation and cleavage of C–N triple bonds. During our continued interest in the zirconocene-mediated reaction of bis(alkynyl)silanes, 2,5-bis(alkynylsilyl)zirconacyclopentadienes were isolated by reaction of (ArC≡C)2SiMe2 with 0.5 equiv of “CpZr(II)” with high regio- and chemoselectivity, which is significantly dependent on the metal-to-diyne ratio in the process. Further study on these zirconacyclopentadienes demonstrated interesting reactivities and useful applications. Reaction chemistry of bis(alkynyl)silanes mediated or catalyzed by transition metals is in progress.

 

Isolation and Structural Characterization of Active Organometallic Intermediates

Structural characterization of active reaction intermediates in metal-mediated or catalyzed organic synthesis is among the most attractive fields in organic, organometallic and inorganic chemistry. It is a challenging project because the active reaction intermediates are very sensitive towards oxygen and moisture. Most importantly, their isolation and structural characterization are of considerable importance in elucidating the metal-mediated or catalyzed reaction mechanism. Generally, the reaction mechanism is proposed based on the assumption as well as some spectroscopic methods. Accordingly, computational studies based on the hypothesis of model compounds provide a good understanding on reaction pathways. However, the most direct and efficient way explaining metal-mediated or catalyzed reactions is to isolate the truly active species and obtain their X-ray crystallographic data.

The project was initiated in 2007. Our aim is to find new reactions mediated/catalyzed by metal catalysts including those of transition metals and lanthanides, and elucidate the reaction mechanism based on the X-ray structure analysis of active organometallic intermediates.