Catalytic C-H bond activation is a highly attractive strategy in green and sustainable covalent synthesis for drugs, natural products and advances materials from simple organic hydrocarbons. Our program systematically established a revolutionary approach in exploiting synergistic effect between main and transition metal to promote efficient selective C-H activation. The following highlights are our several breakthrough discoveries, which led to several significant contributions in the field of chemical science and catalysis, particularly on the development and the understanding of bimetallic cooperative effect on CH activation. (Total citation more than 200 times with several 11 top prestigious 5% scientific publications. Our other research endeavor is also focused on developing and design novel scaffold of ligand framework with the aim of pushing the boundaries of current concept and chemical knowledge. Some of our current interests include (a) functional linked nitrogen-heterocyclic carbene (NHC) and (b) carbodicarbenes, which were used to isolate uniquely chemical structures and to discover interestingly reactivities in transition metals and main group elements. Evidently, our works in CH activation, main group chemistry and ligand design have been recognized with numerous international and national awards as listed below here:
(a) Para-CH bond Activation of Pyridine with Isolation Ni-Al Intermediate
We discovered that the first example of bimetallic Ni-Al catalyst mediated the para-C-H functionalization of pyridinein a selective manner (Scheme R1). In similar studies, we also delivered penetrating new insight on the synergistic effect of a bimetallic in C-H bond activation based on single crystal X-ray diffraction experiment. The success of this program hinges upon a new conceptual paradigm: (a) Acceleration on one of the key steps in catalytic CH activation via Lewis acid, and (b) Steric demanding created by Lewis metal for reinforcing positional selectivity. Our work has been published in Journal of the American Chemical Society. Central to the implication on our discovery is pervasive (total citations = 61 times), as many researchers have implemented our bimetallic concept into their catalysis effort.
(b) Double CH Activation
In the interest of constructing C-C bonds in a more atom- and step-economical fashion, we also developed efficient Pd-catalyzed double C-H activation of cross coupling of heteroarenes with styrenes and other olefinic substrates. This alkenylation paradigm encompasses a wide range of substrate scopes and provides a straightforward and high valued synthetic approach toward C2-E-alkenylated azole motifs. This work has been selected as the highlight in the back cover of the Chemical Communication.
(c) Functional Linked Amino-NHC: Organic Catalysis and Medicinal Implications
Our lab is a pioneer of designing a myriad of amino-NHC frameworks and investigating of their fundamental chemical reactivities, which we have made numerous significant contributions and innovations in the context of molecular catalysis, synthetic chemistry, medicinal and main group elements as illustrated in Scheme R5 with high number of citation (150 times). For example, Anti-cancer agents: Amino-NHC Gold Complexes (Scheme R5a) was developed to have the capacity to induce apoptosis through a p53-bak pathway, a sensational finding that could serve as a new alternate strategy to reduce the resistance of cancer cells to p53-induced apoptosis. The anti-tumor pathway is uniquely different from classical drug cis-platin.
We also have used Amino-NHC to perform “Metal-Free” catalytic process. For the first time, amino-NHC has been shown to mediate the direct C–H functionalization of benzene and pyridine in the absence of a metal catalyst (Scheme R5(c)). Using Electron Spin Resonance, a state of art technique, we have demonstrated the first spectroscopic evidence confirming the radical intermediate in this process, setting a ground breaking work for many other works in this field, namely “metal-free” catalytic C-H bond activation. Furthermore, this versatility of amino-NHC catalyst is also witnessed in C-C, C-B and C-N bond formation (Scheme R5(b)).
(d) Creative Ligand Design Approach: Carbodicarbene and Elusive Boron species
Recently, we have designed another novel ligand with interesting framework called carbodicarbene. In our main group metal’s endeavor, we have discovered the formation of a hitherto unknown three-coordinate dicationic hydrido boron complex with unique bonding environment (Scheme 5). Supporting ligand carbodicarbene gave unprecedented reaction with BH3 without using more highly electrophilic Lewis acid precursors. A reaction behavior not observed for other common NHC ligands. These results pave the way for future studies in highly electrophilic Lewis acid chemistry with interesting potential applications in organic synthesis and catalysis.
(e) Isolation of Novel Pincer bis-(pyridine)carbodicarbene Framework and Highly Efficient Cross-Coupling
The simple synthetic development of acyclic pincer bis(pyridine)carbodicarbene is realized on our endeavor on the ligand design. Presented is the first isolated structural pincer carbodicarbene with a C-C-C angle of 143°, larger than the monodentate framework. More importantly theoretical analysis revealed that this carbodicarbene embodies a more allene-like character. Pd complexes supported by this pincer ligand are active catalysts for Heck-Mizoroki and Suzuki-Miyaura coupling reactions
(f) Expanding Ligand Framework Diversity of Carbodicarbenes and Direct Observation of Boron Activation in Methylation of Amines with CO2
A simple and convergent synthetic strategy was developed to increase the diversity of the carbodicarbene framework by incorporation of unsymmetrical units. Reactivity studies revealed that carbodicarbenes are competent organocatalysts for amine methylation using CO2 as a synthon.
(g) Isolation of Tridentate Acyclic Bis(Pyridine)carbodicarbene and Further Studies on Its Structural Implications and Reactivities
The simple synthetic development of acyclic pincer bis(pyridine)carbodicarbene is depicted herein. Presented is the first isolated structural pincer carbodicarbene with a C-C-C angle of 143°, larger than the monodentate framework. More importantly theoretical analysis revealed that this carbodicarbene embodies a more allene-like character. Pd complexes supported by this pincer ligand are active catalysts for Heck-Mizoroki and Suzuki-Miyaura coupling reactions.