Research

Accessing high-energy molecular architectures and reactive intermediates from stable and readily available starting materials remains a fundamental challenge in synthetic chemistry. Conventional organic synthesis generally relies on thermodynamically favorable pathways, limiting access to transformations and products that lie beyond equilibrium constraints. We aim to develop new strategies for “uphill synthesis,” in which controlled energy input is used to convert stable feedstocks into higher-energy products and reactive intermediates. Our research group explores complementary approaches to achieve this goal through chemical modification  strategies and photo-induced activation methods.

The synthesis of structurally complex molecules from stable and readily available starting materials often requires carefully designed strategies to increase molecular reactivity. Our group explores chemical modification as a means of storing or introducing chemical energy into molecular structures, enabling otherwise challenging transformations.

One approach is based on intrinsic activation through molecular strain. In our work with azabicyclo[1.1.0]butanes (ABBs) (JACS, 2023 and Angew, 2026), the substantial strain energy of the bicyclic framework is harnessed to drive strain-release functionalization, providing efficient access to decorated azetidines and other structurally complex molecules. This strategy demonstrates how molecular strain can serve as a built-in source of chemical energy for molecular construction. We also investigate transient activation, in which stable molecules are temporarily converted into more reactive species. For example, ketones can be transformed into pro-aromatic dihydroquinazolinone (DHQZ) derivatives, which serve as versatile precursors for radical transformations (Org. Lett., 2022). Similarly, thiols can undergo transient chemical modification to form activated perfluoroaryl sulfide species, enabling C–S bond activation and subsequent radical chemistry (JOC, 2022). These approaches allow stable functional groups to be temporarily converted into reactive intermediates and subsequently transformed into valuable molecular structures.

Together, these strategies demonstrate how chemical modification can be used to encode, store, or temporarily introduce reactivity, providing new pathways for converting stable feedstocks into higher-energy intermediates and structurally complex products.

We harness light as an external source of energy to access reactive states and transformation pathways that are difficult to reach under conventional thermal conditions. Our research investigates how molecular systems can absorb, transfer, and utilize photon energy to generate highly reactive intermediates in a controlled manner.

Our work encompasses several complementary modes of photo-induced activation, including direct excitation (JACS, 2025), photosensitization (Green Chem., 2022), and electron donor–acceptor (EDA) complex formation (Org. Lett., 2025). These approaches allow us to generate radical and excited-state intermediates without relying solely on conventional thermal activation.

These strategies enable the development of light-driven transformations under mild conditions and provide access to reactive intermediates and reaction pathways that are challenging to achieve using conventional thermal methods. By controlling the absorption and utilization of light energy, we aim to expand the scope of synthetic transformations accessible through photochemical activation.