The C–H formylation of pyridines represents a valuable strategy for pyridine functionalization,as the resulting formylated pyridines can serve as versatile synthetic linchpins,enabling diverse transformations via the...The C–H formylation of pyridines represents a valuable strategy for pyridine functionalization,as the resulting formylated pyridines can serve as versatile synthetic linchpins,enabling diverse transformations via the formyl group.However,methods for regioselective meta-and para-formylation of pyridine have remained unexplored,and site-switchable strategies for introducing the same functional group are still scarce.Herein,we report a site-switchable metaand para-C–H formylation of pyridines proceeding via oxazino pyridine intermediates.The regioselectivity was precisely dictated by employing CHBr_(3)or CH_(3)OH as masked formyl equivalents under readily tunable conditions.This strategy enabled regioselective access to a structurally diverse array of formylated pyridines,while offering operational simplicity,broad functional group tolerance,scalability,and compatibility with late-stage modifications.Furthermore,the broad synthetic utility of formylated pyridines significantly enhanced the value of this method beyond mere formylation.Together with established ortho-formylation protocols,this work expands the synthetic toolbox for regioselective pyridine formylation,further broadening the accessible pyridine chemical space for applications in drug discovery and materials science.展开更多
基金grant from Deutsche Forschungsgemeinschaft(DFG),Germany(grant no.STU 280/31-1)the Alexander von Humboldt Foundation,Germany(post-doctoral fellowship to S.-M.Guo).
文摘The C–H formylation of pyridines represents a valuable strategy for pyridine functionalization,as the resulting formylated pyridines can serve as versatile synthetic linchpins,enabling diverse transformations via the formyl group.However,methods for regioselective meta-and para-formylation of pyridine have remained unexplored,and site-switchable strategies for introducing the same functional group are still scarce.Herein,we report a site-switchable metaand para-C–H formylation of pyridines proceeding via oxazino pyridine intermediates.The regioselectivity was precisely dictated by employing CHBr_(3)or CH_(3)OH as masked formyl equivalents under readily tunable conditions.This strategy enabled regioselective access to a structurally diverse array of formylated pyridines,while offering operational simplicity,broad functional group tolerance,scalability,and compatibility with late-stage modifications.Furthermore,the broad synthetic utility of formylated pyridines significantly enhanced the value of this method beyond mere formylation.Together with established ortho-formylation protocols,this work expands the synthetic toolbox for regioselective pyridine formylation,further broadening the accessible pyridine chemical space for applications in drug discovery and materials science.
