Yi He, Yuta Kato, Hong Lu, Takashi Kurogi, Yihang Zhang, Yuxuan Yang, Hideki Yorimitsu, Hao Wei
Despite the prevalence of furans in organic chemistry, their direct conversion into diverse heterocycles via oxygen transmutation remains a formidable challenge. This limitation is primarily attributed to the robust endocyclic C-O bonds, its aromaticity, and the lack of strategies to activate inert oxygen atoms. In this study, we report a lithium-mediated strategy that enables the divergent transmutation of furan oxygen atoms. By employing a mechanochemical ball-milling protocol, we achieve this transformation under mild and operationally simple conditions, significantly enhancing the efficiency compared to conventional solution-phase methods. This approach enables the precise replacement of oxygen with diverse elements-including silicon, carbon, selenium, phosphorus, germanium, and titanium-via deoxygenatively dilithiated intermediates that react in situ with various electrophiles, thereby providing direct access to a library of valuable heterocycles. This work highlights a versatile platform for molecular diversification with endocyclic transmutation, demonstrating that mechanochemistry can serve as an operationally efficient and time-saving strategy for complex heterocycle synthesis.