In the 1950s, the arene activation method by means of π-coordination of transition metals with aromatic rings emerged. However, such activation method was difficult to be developed into catalysis, and therefore, relevant research studies became scarce after 2000. In 2020, Hang Shi’s team of Westlake University made a breakthrough by using a transition metal catalyst ligated with hemilabile ligands, and rekindled interests in this field. Very recently, this achievement was selected in the Virtual Issue of Outstanding Work Published in 2020 by Early Career Investigators in the Journal of the American Chemical Society (JACS).

This collection is an annual selection of papers published in the JACS in the previous year. It aims to highlight those important discoveries made by young groups in the early stages of research in various chemical subfields around the world. 

In 2020, over 2000 papers were published in JACS. 27 papers were chosen for this collection, and only 4 papers were related to organic synthetic chemistry. One of them, Ru(II)-Catalyzed Amination of Aryl Fluorides via 6-Coordination , was contributed by Shi’s team. 

Melanie Sanford, associate editor at JACS and professor at University of Michigan commented on the importance of this work, "Nucleophilic aromatic substitution (SNAr) of aryl fluorides as the limiting reagents was realized by 6 ruthenium complexes activation of aryl fluorides. Such a process was achieved in a catalytic fashion by turnover of the stable metal complexes. The authors solved this challenge through a hemilabile ligand design." 

Aromatic compounds such as benzene and toluene, are organic molecules isolated from coal tar or natural gums in ancient times. Meanwhile, aromatic compounds are widely applied in the chemical industry related to materials, pharmaceuticals, and perfumes. For instance, about 80% medicine molecules contain aromatic rings in their structures.

Chemists have worked hard to develop new synthesis methods to modify and funcionalize aromatic rings for more than a century. In the 20th century, chemists found that some transition metals (such as palladium and nickel) could react with aryl halides to generate aryl metal complexes through a metal-engaged carbon–halogen cleavage. Such reactive complexes could further react with a series of coupling reagents, affording aromatic derivatives with different structures and substituents. Based on these findings, chemists established the transition-metal-catalyzed cross-coupling strategy that featured a series of arene functionalization reactions, which had been widely applied so far. In 2010, the Nobel Prize in Chemistry was awarded to three outstanding chemists for palladium-catalyzed cross couplings in organic synthesis. Since 2000, the carbon–hydrogen bond cleavage merged as another broad interest in organometallic chemistry and homogeneous catalysis, and man y relevant catalytic reactions have been developed.

In general, models of arene activation by transition metals can be divided into two categories: one is the aforementioned transition-metal-catalyzed cross-coupling, in which the metal catalyst selectively cleaves a σ-bond on aromatic rings to generate aryl metal species; the other is the π-bond activation through π-coordination of a transition metal. Although the later one can date back to the 1950s, only very limited success has been achieved in the development of catalysis until now.

I n 2020, Hang Shi’s team from Westlake University established a ruthenium-catalyzed nucleophilic aromatic substitution (SNAr) through π-coordination strategy, which not only solved a long-standing challenge in the field of arene activation but also provided a new opportunity for the precise synthesis of molecules bearing aromatic rings. This achievement which was selected into the virtual issue of outstanding work published in 2020 by early-career investigators in JACS is the first publication of Shi’s team (The first author is Dr. Qikai Kang, and the corresponding author is Prof. Hang Shi). In detail, the authors found that a hemilabile ligand could benefit the catalysis in two ways: a side chain group of the ligand that coordinates to ruthenium temporarily could promote product dissociation through steric repulsion; the hemilabile nature provides flexibility to stabilize reaction intermediates, as well as reduces the energy cost in the coordination of substrates to the catalyst.

In addition, Shi’s team further expanded the scope of the above mentioned activation strategy and found that a transition metal rhodium catalyst could catalyze the hydroxylation of aryl fluorides to afford valuable phenol derivatives. In previous reports, the same hydroxylation can not happen even at 300°C in the absence of the catalyst. Meanwile, they isolated and characterized the reaction intermediate, thus proving an important evidence for a long-standing hypothesis of the reaction mechanism. This work was published in Angewandte Chemie Internation Edition in 2021 (Dr. Qikai Kang and graduate student Yunzhi Ling as the co-authors).

The relevant research works are currently undergoing in Shi’s team. The aim of their research is to design and development of catalysis by means of π-coordination with transition metal catalysts, and as thus pave a new way for synthesis and functionalization of aromatic compounds.