Through the formation of an electron donor–acceptor (EDA) complex, strain‐release aminopyridylation of [1.1.1]propellane with N‐aminopyridinium salts as bifunctional reagents enabled the direct installation of amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in the absence of an external photocatalyst. The robustness of this method to synthesize 1,3‐aminopyridylated BCPs under mild and metal‐free conditions is highlighted by the late‐stage modification of structurally complex biorelevant molecules. Moreover, the strategy was extended to P‐centered and CF3 radicals for the unprecedented incorporation of such functional groups with pyridine across the BCP core in a three‐component coupling. This practical method lays the foundation for the straightforward construction of new valuable C4‐pyridine‐functionalized BCP chemical entities, thus significantly expanding the range of accessibility of BCP‐type bioisosteres for applications in drug discovery.

A photocatalytic double umpolung strategy for the vicinal aminopyridylation of ketones was developed using pyridinium N−N ylides. The inversion of the polarity of the pyridinium N−N ylides by single‐electron oxidation successfully enables radical‐mediated 1,3‐dipolar cycloadditions with enolsilanes formed in situ from ketones, followed by homolytic cleavage of the N−N bond. Intriguingly, the nucleophilic amino and electrophilic pyridyl groups in the ylides can be installed at the nucleophilic α‐position and electrophilic carbonyl carbon, respectively, which are typically inaccessible by their innate polarity‐driven reactivity. This method accommodates a broad scope, and the utility was further demonstrated by the late‐stage functionalization of complex biorelevant molecules. Moreover, the strategy can be successfully applied to enamides.

Through the formation of an electron donoracceptor (EDA) complex, strain-release aminopyridylation of [1.1.1]propellane with N-aminopyridinium salts as bifunctional reagents enabled the direct installation of amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in the absence of an external photocatalyst. The robustness of this method to synthesize1 ,3-aminopyridylated BCPs under mild and metal-free conditions is highlighted by the late-stage modification of structurally complex biorelevant molecules. Moreover,t he strategy was extended to P-centered and CF 3 radicals for the unprecedented incorporation of such functional groups with pyridine across the BCP core in at hreecomponent coupling.T his practical method lays the foundation for the straightforwardc onstruction of new valuable C4pyridine-functionalized BCP chemical entities,t hus significantly expanding the range of accessibility of BCP-type bioisosteres for applications in drug discovery.

The photoinduced C4-selective C–H borylation of pyridines was achieved using electron donor–acceptor complexes derived from a Lewis base and N-amidopyridinium salts under external oxidant- and photocatalyst-free conditions. Notably, the nucleophilic character of phosphite-ligated boryl radicals enables addition of a radical to position C4 of pyridinium salts to afford C4-borylated heteroarenes that are otherwise difficult to obtain. This approach provides a versatile platform for the installation of both phosphite- and amine-coordinated boron groups on a series of pyridines under mild conditions, demonstrating excellent C4-positional selectivity for the pyridine scaffolds.