A photoredox/nickel-catalyzed chloroacylation of alkynes with acyl chlorides is described. Acyl chlorides serve as bifunctional reagents to install acyl and chlorine groups across terminal and selected internal alkynes, affording synthetically useful βchloroenones in moderate to good yields. The vinyl chloride motif enables further palladium-catalyzed diversification, and preliminary mechanistic studies are consistent with a radical pathway involving an acyl-nickel species.
Indolylphosphines have proven to be highly versatile ligands for palladium-catalyzed cross-coupling reactions. This short review covers the major developments in this area from mid 2015 to early 2026, emphasizing how recent innovations in ligand design have substantially improved reaction efficiency, expanded the scope of compatible coupling partners, and enabled challenging transformations under milder conditions. Structural motifs responsible for enhanced catalytic activity are highlighted, underscoring the ongoing impact of indolylphosphines in advancing cross-coupling methodology.
We report a photochemical strain-release strategy for the synthesis of 2-azanorbornanes from N-cyclopropylsulfonamide derivatives. Under acridinium photoredox catalysis in the presence of ZnCl2, single-electron oxidation of the cyclopropylsulfonamide initiates a radical cascade that furnishes the bridged aza-bicyclic core under mild conditions. The method provides modular access to substitution at C1, C3, C4, C5, and C7 of the 2-azanorbornane scaffold and delivers C3-substituted products with complete endo diastereoselectivity, complementary to the selectivity typically observed in aza-Diels-Alder approaches. The reaction is amenable to continuous-flow scale-up, and the resulting products can be converted into valuable 2-azanorbornane building blocks, including C1 and C3-endo α-amino acid derivatives. Mechanistic studies support a key role for ZnCl2 in enabling productive single-electron oxidation and identify product degradation pathways that inform reaction optimization. Overall, this work establishes a modular and operationally simple entry to a privileged saturated aza-heterocycle.
The palladium-catalyzed synthesis of deuterated aromatics through deoxygenative deuteration of aryl nonaflates has been achieved in good to high yields with high D contents. In this process, a variety of functional groups and heterocyclic moieties were well tolerated, and the double incorporation of deuterium also proceeded smoothly. As well as the synthesis of a deuterated estrone derivative, the gram-scale experiment was conducted with sufficient efficiency, showing the promising potentiality of this method.
DNA-encoded libraries (DELs) have transformed early-stage drug discovery by enabling the rapid screening of vast chemical spaces through affinity selection. However, their structural diversity and functional complexity remain constrained by the limited scope of DNA-compatible reactions and the reliance on prefunctionalized building blocks. Functional group transformations (FGTs) have emerged as a versatile yet underexplored strategy for expanding the synthetic capabilities of DELs beyond conventional building-block-driven assembly. By selectively controlling functional-group reactivity, converting readily available functionalities into alternative synthetic handles, and directly remodeling preassembled molecules, FGTs enable molecular diversification at multiple stages of DEL synthesis. In this Review, we present a conceptual framework for on-DNA FGTs based on three complementary synthetic roles: reaction control through functional-group unmasking, chemical-space expansion through functional group interconversion, and function-oriented molecular editing through late-stage functionalization. Together, these strategies highlight how FGTs can extend DEL synthesis toward more programmable and function-oriented molecular diversification.
