Transition Metal-free Cross-Coupling Reactions Catalyzed by Aluminyl Anions

The aim of this research program is to develop an efficient catalytic system for versatile cross-coupling reactions promoted by anionic aluminum species [Al]–M+. Transition metal-mediated cross-coupling reactions are powerful tools for the construction of carob-carbon bonds, and indeed various pharmaceutical and agrochemical compounds are currently manufactured by employing the cross-coupling methods. While a variety of metal complexes that enable cross-coupling reactions have been reported thus far, the cost of transition metal complexes consisted of metal and specific ligands is essentially high, and many metals are often toxic. Therefore, the development of catalysts constructed by earth-abundant cheap elements, instead of expensive transition metals, is highly desirable from both economical and environmental points of view. In this project, we develop a transition metal-free methodology for cross-coupling reactions. By incorporating aluminum into the cyclic (alkyl)(amino) framework, various anionic aluminum species [Al]–M+ can be readily synthesized. The dicoordinate aluminum center of [Al]–M+ possesses both a lone pair of electrons and an unoccupied p-orbital, being isoelectronic with carbenes. The anionic nature of the aluminum center exhibits strong nucleophilicity and it undergoes the substitution reaction with haloarenes Ar-X to afford the corresponding derivative [Al]-Ar. Subsequent nucleophilic attack by organometals R’-M to the neutral and tricoordinate aluminum center of [Al]-Ar yields an ionic tetracoordinate aluminum species [[Al]-Ar(R’)]–M+, from which reductive elimination of the Ar and R’ fragments may give rise to the coupling product Ar-R’, concomitant with the reproduction of [Al]–M+. The elementary step should be applicable to the one-pot reaction and even a catalytic process. Because aluminum is abundant, cheap and not toxic compared with transition metals, the proposed systems for the cross-coupling reactions may be carried out under the economical conditions compared with extant conventional methods. Moreover, the coupling product can be utilized various synthetic building blocks for organic synthesis, drug, pharmaceutical and agrochemical compounds, which will provide a practical opportunity to use our system in industrial processes.