Sangwon Seo

β ‐Methylene carbonyl motifs constitute privileged structural frameworks that play vital roles as a pharmacophore and serve as key intermediates in the assembly of architecturally complex molecules. Despite their synthetic importance, asymmetric approaches for their preparation remain scarce and are largely confined to substrate‐controlled or stoichiometric chiral auxiliary methods. Herein, we report a nickel hydride‐catalyzed enantioconvergent α ‐alkenylation of carbonyl compounds with alkynes, providing a direct and general route to α ‐chiral β ‐methylene carbonyl derivatives. The transformation proceeds via Markovnikov‐selective alkyne hydronickellation followed by nickel‐radical recombination to forge the α ‐stereogenic center, delivering the desired products with high levels of regio‐ and enantioselectivity. The protocol accommodates a wide range of alkynes and α ‐halocarbonyl partners, displays excellent functional group tolerance, and can be applied to the modification of biologically relevant molecules. Mechanistic investigations indicate that a partially protic Ni(II)H species governs the observed regioselectivity, while enantio‐discrimination occurs during the radical capture step. This work establishes NiH catalysis as a versatile platform for expanding the synthetic repertoire for enantioenriched β ‐methylene carbonyl architectures.

β ‐Methylene carbonyl motifs constitute privileged structural frameworks that play vital roles as a pharmacophore and serve as key intermediates in the assembly of architecturally complex molecules. Despite their synthetic importance, asymmetric approaches for their preparation remain scarce and are largely confined to substrate‐controlled or stoichiometric chiral auxiliary methods. Herein, we report a nickel hydride‐catalyzed enantioconvergent α ‐alkenylation of carbonyl compounds with alkynes, providing a direct and general route to α ‐chiral β ‐methylene carbonyl derivatives. The transformation proceeds via Markovnikov‐selective alkyne hydronickellation followed by nickel‐radical recombination to forge the α ‐stereogenic center, delivering the desired products with high levels of regio‐ and enantioselectivity. The protocol accommodates a wide range of alkynes and α ‐halocarbonyl partners, displays excellent functional group tolerance, and can be applied to the modification of biologically relevant molecules. Mechanistic investigations indicate that a partially protic Ni(II)H species governs the observed regioselectivity, while enantio‐discrimination occurs during the radical capture step. This work establishes NiH catalysis as a versatile platform for expanding the synthetic repertoire for enantioenriched β ‐methylene carbonyl architectures.

The formation of multiple and remote C–C bonds remains highly challenging owing to difficulties in reactivity and selectivity control. Herein, we report a nickel‐catalyzed twofold conjunctive cross‐electrophile coupling that employs an alkene and a 1,3‐enyne as conjunctive platforms and alkyl and aryl halides as coupling partners. Through a philicity‐alternating radical relay followed by selective radical capture, the reaction enables the formation of three or more C–C bonds. Combined experimental and theoretical investigations provide a rationale for the sequential radical additions to the π systems and the selective capture of a radical intermediate by the nickel catalyst. Furthermore, a five‐component coupling showcases the sequential and controlled addition of alkyl and aryl moieties across three conjunctive units, demonstrating the synthetic versatility of the twofold conjunctive coupling.

Investigation of the fundamental microscopic processes occurring in organic reactions is essential for optimising both organocatalysts and synthetic strategies. In this study, single‐molecule fluorescence microscopy was employed to study the Diels–Alder reaction catalysed by a first‐generation MacMillan catalyst, providing direct insights into its kinetic dynamics. This reaction proceeds via a series of reversible processes under equilibrium conditions ( S ⇄ IM ₁ ⇄ IM ₂ → P , IM ₁ and IM ₂ : N,O‐acetal and iminium ion intermediates, respectively). The individual reaction trajectories of single molecules were directly observed in real‐time, and the kinetic transitions between the different states were quantitatively analysed using a hidden Markov model, thereby enabling precise determination of the kinetic rate constants and transition probabilities at the single‐molecule level. In particular, the unique structural features of the MacMillan catalyst were probed to reveal how specific interactions stabilise the reaction intermediates and influence their kinetic behaviours. These findings highlight the importance of single‐molecule fluorescence microscopy in understanding the fundamental mechanisms of organic reactions and guiding the rational design of more effective catalysts.

The C–H functionalization of polymers enables the direct incorporation of new functional groups into polymer backbones, presenting significant opportunities for the upcycling of commodity polymers. However, developing reactions that achieve selective functionalization while preserving the intrinsic features of polymers and avoiding undesirable structure deformation remains a considerable challenge. In this study, we present a transition metal-free post-functionalization approach for polyethers via a photoinduced α-C–H amidation reaction. This strategy provides a route to previously unattainable α-amino polyethers, which exhibit distinct physical properties from those of the parent polymer. By leveraging a polar-radical relay mechanism, we effectively incorporate C–N bonds into the polyether backbone while suppressing degradation and cross-linking. Conducted under mild and convenient conditions, this approach demonstrates significant site selectivity at the ethereal α-position, even in the presence of other types of C–H bonds, achieving tailed post-functionalization of macromolecules. Furthermore, the present strategy holds promise for broader applications, including the amidative degradation of commodity polymers and transformation of polyethylene glycol (PEG) network.

Over the past few years, earth-abundant transition metal-catalyzed hydrosilylation has emerged as an ideal strategy for the synthesis of organosilanes. The success in this area of research has expanded to the advancements of alkyne dihydrosilylation reactions, offering broadened synthetic applications through the selective installation of two silyl groups. In particular, catalysts based on Fe, Co, and Ni have engendered enabling platforms for mild transformations with a range of distinct regioselectivity. This mini-review summarizes recent advances in this research field, highlighting the unique features of each system from both synthetic and mechanistic perspectives.