Research Projects

Captivated by CRISPR gene editing, synthetic organic chemists are increasingly focused on developing analogous molecular editing strategies that enable late-stage skeletal remodeling of complex molecules—offering a modular alternative to traditional multistep de novo synthesis. This proposal aims to develop atom-insertion-based skeletal editing methodologies centered on main group elements—nitrogen, carbon, and boron—by harnessing the unique reactivities of nitrene, metal carbenoids, and borylene. These tools will enable direct access to emerging heterocyclic scaffolds with high potential in drug discovery and material science. Specifically, the proposal targets – firstly, nitrogen atom insertion to develop a hypervalent iodine-mediated two-fold nitrogen atom insertion strategy across both α C–C bonds of ketones using proaromatic compounds, enabling direct access to aza-isosteres of quinazoline-2,4-dione scaffold in (pre)clinical drugs and natural products. Building on our success, the N-insertion strategy will further be extended to (de)conjugated butenolides to access oxazinones and subsequently pyridines. Secondly, catalytic generation of metal-carbenoids from halo-substituted ynamides or (ethynyloxy)arenes and pyridine N-oxides will be explored. Unlike hazardous diazo or diazirine reagents, these C-atom donors offer built-in amide or ester functionalities for downstream synthetic elaboration. The feasibility of this C-insertion approach will be validated through N–N bond insertions in azoles, enabling carbon incorporation in heterocyclic frameworks. Thirdly, the generation of borylene species from dibromoaryl(alkyl)boranes and their insertion into proaromatic substrates under unified metallaphotoredox catalysis will enable access to 1,2-BN isosteres of underexplored heteroaromatic scaffolds such as (benzo)carbazoles and dibenzothiophenes—structures with promising applications in both therapeutics and optoelectronic materials. The proposed work will leverage the underutilized reactivity of proaromatic compounds—well-known for inert C–C bond activation but largely unexplored in skeletal editing. By integrating the reactivities of nitrene, metal-carbenoids, and borylene with proaromatic frameworks, this proposed plan introduces a unified and modular platform for constructing novel heterocycles that are otherwise synthetically challenging. It will open untapped chemical space, especially for nitrogen-, carbon-, and boron-based edits, and provide a new approach to functionalize complex molecules in a modular and late-stage manner. The success of this proposal will contribute significantly to the fields of synthetic chemistry, drug discovery, and material science—addressing key challenges in precision molecular editing and unlocking new opportunities for therapeutic and optoelectronic material advancement.