The three-component dialkylation of alkenes provides an efficient strategy for constructing C(sp3)–C(sp3) bonds, facilitating the synthesis of complex molecules such as pharmaceuticals, natural products, and functional materials. Nevertheless, key challenges persist, including precise regiocontrol, suppression of β-hydride elimination, and minimization of side reactions. Recent advances in radical chemistry and transition-metal catalysis have considerably expanded the scope of this methodology for both activated and unactivated alkenes. This review systematically summarizes recent progress in this field, with emphasis on mechanistic insights, substrate applicability, and innovative strategies for controlling regio- and stereoselectivity. Finally, current limitations are evaluated, and promising future research directions are proposed.

Photoredox-catalyzed dicarbofunctionalization of alkynes has emerged as a cutting-edge research direction in organic synthesis.This strategy ingeniously integrates the mild activation capabilities of photochemistry with the efficient bond-forming characteristics of transition metal catalysis.Through mechanisms such as single-electron transfer,energy transfer,or proton-coupled electron transfer,highly selective dicarbofunctionalization of alkynes can be achieved under visible light conditions.Compared with traditional methods,this approach not only offers mild reaction conditions and excellent functional group tolerance,but also enables precise control over chemo-,regio-,and stereoselectivity,thereby providing a new paradigm for the efficient synthesis of polysubstituted alkenes,cyclic compounds,and bioactive molecules.This review systematically summarizes the latest advances in this field with a focus on the substrate scope,reaction mechanisms,strategies for selectivity control,and synthetic applications,while also offering perspectives on future development trends.

Electron donor-acceptor (EDA) complex photochemistry has emerged as a powerful strategy for expanding the potential of visible light-driven radical synthetic chemistry. This photochemical strategy intrinsically differs from photoredox catalysis since it does not rely on the use of exogenous photocatalysts. The majority of reported EDA complex-driven photosynthesis rely on the use of stoichiometric electron-donor and acceptor substrates, leading to a limited efficiency and scope of the photochemical processes. An important advance is to implement the EDA complex photochemistry within a catalytic regime, where either the donor or acceptor is employed catalytically. This approach provided opportunities to expand the efficiency and versatility of the EDA complex photochemistry, while implementing asymmetric radical processes by using a chiral catalyst. The aim of this review is to highlight the recent advances in catalytic EDA complex photochemistry. The review is organized into two primary categories: reactions mediated by catalytic electron donors and those by catalytic electron acceptors. We focus on the discussion of different EDA catalysis models and reaction mechanisms. Finally, the review concludes with an analysis of prevailing challenges and perspectives on future research directions.

1,3-Dienes represent a class of abundant and versatile chemical feedstocks for constructing complex chiral allylic compounds, privileged structural motifs widely found in natural products and bioactive molecules. However, their multiple reactive sites pose a fundamental challenge to asymmetric functionalization. Traditional methods are often limited by issues such as poor selectivity, harsh reaction conditions, and unwanted byproduct formation. In recent years, visible-light-driven transition metal catalysis has emerged as a powerful strategy that enables precise control of the stereoselectivity under mild conditions, garnering significant attention. This review systematically summarizes recent advances in catalytic asymmetric functionalization of 1,3-dienes involving photoredox/palladium, copper, or chromium combinations, with a focus on reaction mechanisms, substrate adaptability, and synthetic applications. It aims to provide fundamental insights for the development of novel and efficient asymmetric catalytic methods for the transformation of 1,3-dienes.

Five- and six-membered benzo-fused lactams are important and prevalent scaffolds in many natural products and biologically active compounds. In spite of considerable advances in their synthesis, the intramolecular alkene functionalization preferably goes through 5-exo-trig cyclization to afford five-membered ring products, while the kinetically disfavored 6-endo-trig cyclization remains largely elusive. Herein, we report a novel catalyst-controlled 5-exo/6-endo regiodivergent intramolecular aryl-aminoalkylation of alkenes. The present method affords a variety of five- and six-membered N-heterocycles simultaneously from the same simple starting materials, and both products are very useful building blocks in organic synthesis. The computational studies reveal that the bonding affinity of the alkyl radical to the metal center is the primary factor behind the divergent regioselectivity. The stronger bonding affinity to the Ni center, than that to the Pd center, causes the Ni-catalyzed reaction to commence with C-Br bond cleavage to provide an aryl radical via an outer-sphere single electron transfer (OSET) pathway, while the Pd-catalyzed reaction begins with the Giese addition of an alpha-amino radical to the terminal position of alkenes.

We report herein the first reductive alkylation/aldol reaction via dual nickel/photoredox catalysis. This catalytic strategy completes the traditional approaches that require the performance of reactive organometallic reagents. By the simple assembly of unactivated alkyl halides, α,β-unsaturated carbonyls, and aldehydes in one-pot reaction, a variety of synthetically valuable β-hydroxyl carbonyl compounds can be synthesized under mild conditions with moderate to good yields. The reaction features a broad substrate scope and functional group tolerance. Both aromatic and aliphatic aldehydes and 1°, 2°, and 3° alkyl bromides are all compatible with this catalytic system.

A highly branch-regioselective allylic aminoalkylation reaction has been developed through dual chromium/photoredox catalysis, providing an economical and sustainable alternative to conventional methods that rely on noble transition metals, such as palladium. This transformation proceeds under mild conditions and enables the radical coupling of readily accessible allylic bromides with α-silylamines, yielding a diverse range of synthetically valuable branched homoallylic amines. Notably, the method features a broad substrate scope and excellent functional group tolerance, accommodating various aromatic and aliphatic allylic bromides as well as diverse N-heterocyclic amines.

Chiral gamma-amino acids are among the most valuable and ubiquitous structural units in natural products, pharmaceuticals and many physiologically active compounds. Herein, we demonstrate a convenient synthetic approach to chiral gamma-amino acid structures via an asymmetric aryl-aminoalkylation of alkenes enabled by a dual photoredox/nickel catalysis. Taking advantage of the mild and redox-neutral condition, high levels of enantiocontrol of alpha-carbonyl benzylic stereocenters are obtained. Experimental and computational mechanistic studies were performed to gain insights into the mechanism and origin of enantioselectivity. The results reveal that the reaction follows a Ni(0)/Ni(I)/Ni(III)/Ni(I) catalytic cycle and C-X bond oxidative addition is the enantiodetermining step.

beta-Amino acid-containing structures show important biological activity and are found widely in many pharmacologically active compounds; therefore, the development of efficient methods for the synthesis of beta-amino acid derivatives has evoked considerable interest in the past decades. Herein, we report a nickel/photoredox-catalyzed synthesis of beta-amino acid derivatives from readily available alkyl redox-active esters, alkenes, and alpha-silylamines. This reaction is characterized by a broad substrate scope, mild conditions, and excellent selectivity. Mechanistic studies suggest that the reaction proceeds through a radical pathway.

Catalytic electron donor-acceptor (EDA) complex photochemistry has recently emerged as a popular and sustainable alternative to photoredox synthetic methods. Yet, the catalytic EDA strategy is still in its infancy for organic synthesis due to the challenges of designing novel catalytic paradigm and expanding the substrate and reaction scope. Here, we disclose a catalytic EDA/Cu cooperative strategy by employing NaI as a catalytic donor for copper-catalyzed radical asymmetric carbocyanation. A diverse range of synthetically useful chiral benzyl nitriles are produced with high enantioselectivities. This synergetic EDA/copper catalysis enables the decarboxylative cyanation without request of any photoredox catalysts, further expanding the synthetic potential of catalytic EDA chemistry in organic synthesis. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

The dehydrogenative coupling of silanes with alcohols represents an atom-economical and environmentally benign approach for the synthesis of organosilicon, which are widely utilized in organic synthesis, surface modification, and functional material design. In response to the demand for efficient and sustainable catalytic systems, this study reports the innovative construction of a series of layered WXS2 catalysts featuring acid-base cooperative catalytic sites. A microwave-assisted calcination strategy was employed to achieve precise modulation of the acid and base active sites, enabling structural and functional tunability. Comprehensive characterization revealed that the W6+/W4+ ratio plays a pivotal role in determining the surface acidity of the catalysts. Moreover, pyridine and pyrrole poisoning experiments were conducted to clarify the cooperative effect between acidic and basic sites in governing both catalytic activity and selectivity. Isotope-labeling experiments with 18O further unveiled the mechanistic impact of acid-base site ratios on the reaction pathway, and a dual-site catalytic mechanism was proposed, in which acidic sites activate Si-H bonds while basic sites enhance the nucleophilicity of alcohols. These insights collectively provide a theoretical foundation and practical guidance for the development of high-performance, non-noble-metal catalytic systems for silane transformations.

Propynylamines are prevalent structures widely existing in biologically active compounds and natural products. In this study, we present a novel alkynylation approach for synthesizing propargylamines by cross-coupling of alkynyl bromides and alpha-silylamines via a nickel metallaphotoredox catalysis. A diverse range of N-heterocyclic and acyclic alpha-silylamines, along with aromatic and aliphatic alkynyl bromides, are nicely incorporated, delivering structurally diverse propargylamines in moderate to good yields. Mechanistic studies suggest that the reaction proceeds through a radical pathway.

A dual nickel/photoredox‐catalyzed reductive aldol reaction using readily available alkyl bromide and α‐silylamine as bench‐stable hydride source and organic reductant is reported. A variety of β‐hydroxyl carbonyl compounds can be efficiently synthesized under mild conditions. The reaction exhibits broad substrate scope, accommodating various (hetero)aromatic and aliphatic aldehydes, as well as acyclic and cyclic α,β‐unsaturated carbonyls.

Herpesviruses, including α-herpesvirus and herpes simplex virus (HSV-1), are masters of immune evasion. Previously we demonstrated that CD1d-restricted NKT cells are required for optimal anti-HSV-1 immune responses and HSV-1 efficiently downregulates CD1d to suppress NKT cell function. To delineate how the virus evades NKT cell function and establishes infection in vivo, we screened an HSV-1 expression library to identify the viral gene(s) downregulating CD1d and discovered that a leaky late gene, UL56, most efficiently suppresses CD1d expression by degrading the protein, apparently via both proteasome- and lysosome-dependent pathways. To investigate the molecular mechanism of UL56 suppression of CD1d expression, we purified and identified UL56-associated proteins by mass spectrometry. The most abundant associated proteins were members of NEDD4 E3 ubiquitin ligase family. Interestingly overexpression of one member, NEDD4L is sufficient to downregulate CD1d expression. However, different from the K5 protein from Kaposi sarcoma's herpesvirus (KSHV), UL56 and NEDD4L did not directly ubiquitinate CD1d. CD1d protein lacking the key lysine residue in its cytoplasmic tail is similarly downregulated by UL56 and NEDD4L protein. Co-expression of UL56 and NEDD4L synergistically reduced the CD1d expression, suggesting that UL56 collaborates with NEDD4L to downregulate CD1d. During in vivo infection, UL56-deficient mutant virus showed significantly weaker virulence in NKT-sufficient mice but demonstrated higher virulence in mutant mice lacking NKT cells. All our results supported that at least one of the pathogenesis functions of UL56 is its suppression of NKT cell function during infection. In the large DNA genomes of herpeviruses, there are many genes encoding associate proteins. Most of these proteins are not essential for viral replication but play key roles in viral pathogenesis, in particular, modulating the host immune system to allow efficient viral replication in vivo and latency. The HSV-1 UL56 gene is one of such genes, and its exact pathogenic roles have remain elusive. After we demonstrated the essential roles of CD1d-restricted NKT cells in anti-HSV-1 immunity during HSV-1 ocular infection (P. Rao, X. Wen, J. H. Lo, S. Kim, X. Li, et al., J Virol 92:e01490-18, 2018, https://doi.org/10.1128/jvi.01490-18), we now screened the HSV-1 expression library and identified UL56 is a key factor downregulating CD1d and suppressing NKT cell function. In this manuscript, we are reporting our molecular mechanism study of how UL56 evades CD1d antigen presentation and NKT cell function.

将廉价丰富的原料转化成高附加值的精细化学品是合成化学永恒的主题.氨是化肥工业和有机化工的重要原料,全球每年通过Haber-Bosch法合成氨的总量超过1.82亿吨[1],巨大的产量和低廉的价格使其成为合成含氮化合物的理想原料.以苯胺及其衍生物为代表的芳基伯胺是医药、农药、染料、功能材料及高分子材料中的关键中间体[2].工业上合成苯胺及其衍生物要经过芳烃的硝化和加氢还原过程,硝化过程中作为氮源的HNO3是通过两步Ostwald法制备的(Scheme 1,A)[3],由于使用硫酸和硝酸作为硝化试剂,该工艺反应选择性差,且会产生大量废酸,后处理困难.因此,发展利用廉价易得的氨直接作为氮源合成芳胺及其衍生物的方法是亟待解决的问题.

A ligand-free cross-coupling of vinyl halides and alpha-silylamines toward tertiary allylic alkylamines by merging nickel and photoredox catalysis is developed. A variety of (E)-vinyl electrophiles including conjugate divinyl halides and sterically hindered vinyl halides are coupled smoothly with alpha-silylamines to afford allylic amines under mild conditions with good yields and E-selectivity. Moreover, by simply modifying the photocatalyst or prolonging the irradiation time, the reaction can afford Z-selective allylic amines as major products via photochemically driven E -> Z isomerization. This radical-based coupling strategy provides an alternative and efficient pathway to construct tertiary allylic alkylamines with good and tunable Z/E selectivity.

An efficient visible-light induced nickel-catalyzed reductive Heck reaction of alkenes by using mild organic reductant Hantzsch ester(HEH)instead of traditional metal reductants or hydride reagents was developed.The reductive hydroarylation of acrylates with aryl halides was successfully achieved without requiring exogenous photoredox catalysts.This reaction is highlighted by the simple and mild conditions,good functional group tolerance,thus providing a complementary approach for alkenes reductive Heck reaction.

A new catalytic decarboxylative cyanation and thiocyanation via a synergistic NaI/Cu catalysis is developed. The photoexcited electron donor-acceptor complex by assembly of NaI, R3P, and N-acyloxy-phthalimide ester (NHPI ester) triggers the generation of alkyl radical species, which then engages in Cu-catalyzed radical coupling process. Key to success of this dual catalytic transformation is the reliable charge transfer between I· and Cu(I). This dual catalytic platform can eliminate the use of expensive iridium-based photocatalyst or synthetically elaborate organic dyes. A series of primary, secondary, and tertiary alkyl nitriles and thiocyanates are easily synthesized. Moreover, an asymmetric decarboxylative cyanation by applying a chiral Cu catalyst is also developed to afford chiral nitriles in high enantioselectivity. The mechanistic details and the origin of the high enantioselectivity are further investigated by the mechanistic experiments and the density functional theory calculations.