Understanding reaction mechanisms at the electronic-structure level is fundamental to controlling chemical reactivity and designing new catalysts. Mechanistic insight bridges the gap between empirical observation and molecular-level explanation by revealing key intermediates, transition states, and energy profiles that govern how and why reactions proceed.
In collaboration with Professor Changgui Zhao and Professor Guohua Hou at Beijing Normal University, we has employed density functional theory to elucidate mechanisms of diverse organic and catalytic reactionsfor a variety of challenging organic and organometallic processes [1], [2], [3], [4]. These calculations clarify competing pathways and reveal the origins of selectivity. In the future, we plan to investigate reactions involving transition-metal complexes and photochemical processes, where strong correlation plays a central role.
[m.n]Paracyclophanes ([m.n]PCPs) are widely used in asymmetric catalysis, energy materials, and π-stacked polymers. To date, however, most studies have focused on [2.2]PCPs. The atroposelective synthesis and structural characterization of [m.n]PCPs with variable ansa chain lengths remain underexplored. In this study, we report an N-heterocyclic carbene-catalyzed enantioselective macrocyclization. This method enables the efficient construction of a diverse array of [m.n]PCPs with excellent enantioselectivities. A comprehensive investigation was conducted, including ring strain energy calculations, aromatic interaction energy analysis, racemization barrier measurements, local strain visualization, and systematic geometric analysis. These studies provide detailed insights into the relationship between the macrocyclic structure and properties. The synthetic utility of [m.n]PCPs is demonstrated by a [6.5]PCP-derived thiourea organocatalyst that effectively promotes the asymmetric amination reaction.
@article{Wen2026,author={Wen, Yilu and Yao, Yaqi and Zhong, Yujun and Li, Chenyang and Zhao, Changgui},doi={10.1039/D6SC05207J},issn={2041-6520},journal={Chem. Sci.},month=aug,publisher={Royal Society of Chemistry},title={{Enantioselective synthesis and characterization of [m.n]paracyclophanes}},url={https://pubs.rsc.org/sc/article/doi/10.1039/d6sc05207j},year={2026},}
An unprecedented catalytic kinetic resolution of 2-substituted 3-nitro-2H-chromenes via Rh-catalyzed asymmetric hydrogenation has been developed to simultaneously produce a variety of syn-chiral 2-substituted 3-nitro-2H-chromanes containing vicinal stereogenic centers with excellent diastero- and enantioselectivities [diastereomeric ratio (dr) of >99:1 and up to 99.9% enantiomeric excess (ee)] and recovered chiral 2-substituted 3-nitro-2H-chromenes with 90–99.9% ee in high yields, respectively, achieving excellent kinetic selectivity factors of up to 1057. Moreover, in addition to syn-chiral 2-substituted 3-nitro-2H-chromanes, this new approach provides concise, atom-economical, and straightforward access to anti-chiral 2-substituted 3-nitro-2H-chromanes and a mammalian target of rapamycin (mTOR) inhibitor, (R)-DHM25.
@article{Su2025,author={Su, Yanhao and Xie, Chaochao and Hu, Ziyu and Zi, Guofu and Li, Chenyang and Hou, Guohua},doi={10.1021/acs.orglett.5c00903},issn={1523-7060},journal={Org. Lett.},month=mar,number={12},pages={3095--3100},title={{Diastereo- and Enantioselective Catalytic Kinetic Resolution of 2-Substituted 3-Nitro-2 H -chromenes}},url={https://pubs.acs.org/doi/10.1021/acs.orglett.5c00903},volume={27},year={2025},}
Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process.
@article{Li2024a,author={Li, Jiayan and Dong, Ziyang and Chen, Yang and Yang, Zhanhui and Yan, Xinen and Wang, Meng and Li, Chenyang and Zhao, Changgui},doi={10.1038/s41467-024-46376-8},issn={2041-1723},journal={Nat. Commun.},month=mar,number={1},pages={2338},publisher={Springer US},title={{N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution}},url={https://www.nature.com/articles/s41467-024-46376-8},volume={15},year={2024},}
An N-heterocyclic carbene (NHC)-catalyzed atroposelective macrolactonization has been disclosed. This approach affords planar-chiral macrocycles in high yields with excellent enantioselectivities over a broad substrate scope. Controlled experiments suggest that the enantioselectivity might arise from the cation–n interaction between the acyl azolium and the electron-rich moiety in the substrate. This mechanism is supported by density functional theory calculations, which also suggest an important π–π interaction in stabilizing the transition state.
@article{Wang2024,author={Wang, Jiaming and Wang, Meng and Wen, Yilu and Teng, Peng and Li, Chenyang and Zhao, Changgui},doi={10.1021/acs.orglett.3c04200},issn={1523-7060},journal={Org. Lett.},month=feb,number={5},pages={1040--1045},title={{N-Heterocyclic Carbene-Catalyzed Highly Enantioselective Macrolactonization to Access Planar-Chiral Macrocycles}},url={https://pubs.acs.org/doi/10.1021/acs.orglett.3c04200},volume={26},year={2024},}
