A Ni/photoredox dual catalytic cross-coupling is disclosed in which a diverse range of (hetero)aryl bromides are used as electrophiles, with 1,4-dihydropyridines serving as precursors to Csp3-centered alkyl radical coupling partners. The reported method is characterized by its extremely mild reaction conditions, enabling access to underexplored cores.

Under oxidative conditions, 1,4-dihydropyridines (DHPs) undergo a homolytic cleavage, forming exclusively a Csp3-centered radical that can engage in the C-H alkylation of heterocyclic bases and 1,4-quinones. DHPs are readily prepared from aldehydes, and, considering that aldehydes normally require harsh reaction conditions to take part in such transformations, with mixtures of alkylated and acylated products often being obtained, this net decarbonylative alkylation approach becomes particularly useful. The present method takes place under mild reaction conditions and requires only persulfate as a stoichiometric oxidant, making the procedure suitable for the late-stage C-H alkylation of complex molecules. Notably, structurally complex pharmaceutical agents could be functionalized or prepared with this protocol, such as the anti-malarial Atovaquone and anti-theilerial Parvaquone, thus evidencing its applicability. Mechanistic studies revealed a likely radical chain process via the formation of a dearomatized intermediate and provided a deeper understanding of the factors governing the reactivity of these radical forebears.

A rapid, highly diastereoselective amidoarylation of unactivated olefins was achieved to render medicinally privileged pyrrolidinone structures. Taking advantage of a photoredox proton-coupled electron transfer process, amidyl radicals were obtained from non-prefunctionalized N-H bonds under mild conditions, which were subsequently trapped by pendant olefins, delivering alkyl radicals for nickel-catalyzed cross-coupling. Mechanistic studies revealed the key balance between thermodynamically-driven radical generation and kineticallydriven cyclization, which led to expanding the scope toward urea and carbamate substrates.

The development of synthetic tools to introduce saccharide derivatives into functionally complex molecules is of great interest, particularly in the field of drug discovery. Herein, we report a new route toward highly functionalized, arylated saccharides, which involves nickel-catalyzed cross-coupling of photoredox-generated saccharyl radicals with a range of aryl- and heteroaryl bromides, triggered by an organic photocatalyst. In contrast to existing methods, the mild reaction conditions achieve arylation of saccharide motifs while leaving the anomeric carbon available, thus providing access to a class of arylated glycosides that has been underexplored until now. To demonstrate the potential of this strategy in late-stage functionalization, a variety of structurally complex molecules incorporating saccharide moieties were synthesized.

A Pd-catalyzed C(sp 3 )-H functionalization/carbenoid insertion is described. The method allows for the rapid synthesis of bicyclic frameworks, generating all-carbon quaternary centers via multiple C-C bond-formations in a straightforward manner.