Visible light promoted difunctionalization reactions of alkynes

Visible light promoted difunctionalization of alkynes is reviewed. The difunctionalization reaction is achieved by different reagents. Radicals such as carbon(sp3), carbon(sp2), and other heteroatom(P, S, N, Se, O, and halide) radicals initiated by visible light can undergo radical addition to a carbon-carbon triple bond. Upon further transformation, the desired difunctionalized products are obtained. Some organometallic complexes can be activated by visible light;the difunctionalization of alkynes is catalyzed by these species. Other reagents like 1,3-dipole precursors could also react with alkynes to give difunctionalization products;here, the 1,3-dipole derivatives are obtained by visible light photocatalysis. So far, the strategy has been succeeded in the formation of C–C bonds and C–X bonds. Several valuable chemical skeletons have been constructed under mild conditions. However, high regio-and stereoselectivities in some direct difunctionalization methodologies are yet to be achieved.

Atroposelective Synthesis of 3-Aryl-Indoles Through a One-Pot 2,3-Difunctionalization of Simple Indoles

Indole and its derivatives represent the most important heterocycles that are widely present in bioactive molecules,natural products and advanced materials,and thus functionalization of simple indoles to construct complex indole derivatives is a research area of great current interest.2,3-Difunctionalization of indoles has been extensively studied,but the reported examples are limited to the synthesis of 2,3-disubstituted indole derivatives or dearomatized products containing central chirality.Until now,atroposelective 2,3-difunctionalization of simple indoles for the synthesis of axially chiral molecules is unknown.In this article,we report a straightforward and general strategy for atroposelective 2,3-difunctionalization of simple indoles,forming indole-containing axially chiral products in good yields and excellent enantioselectivities.The strategy we introduce herein may lead to the discovery of new approaches for multifunctionalization of indoles and other heterocyclic scaffolds,thus accessing novel axially chiral heteroarene-containing scaffolds that may find applications in medicinal chemistry and asymmetric catalysis.

Photoinduced difunctionalization with bifunctional reagents containing N-heteroaryl moieties

Bifunctional reagents that serve as dual coupling partners with an activating species have emerged as valuable synthetic tools in organic chemistry.They allow for the development of diverse reaction modes with enhanced efficiency and structural variability,which is in high demand for atom-economic and sustainable synthesis.Among them,bifunctional reagents containing Nheteroaryl groups have received much attention due to their ability to introduce privileged N-heteroaryl moieties into complex molecules that are otherwise challenging to access.Furthermore,these reagents have been employed under visible-light conditions to achieve various synthetic applications,enabling difunctionalization of alkenes,alkynes,and[1.1.1]propellanes under mild reaction conditions,providing access to highly functionalized N-heteroarenes.In this review,we provide an overview of the recent achievements and applications of photoinduced difunctionalization using bifunctional reagents containing N-heteroaryl groups.We systematically categorize the representative contributions in the field based on bifunctional reagents and their reactivity patterns.This review aims to highlight the potential of these reagents as powerful synthetic tools for sustainable and diverse synthesis.

Cobalt-Catalyzed Difunctionalization of Styrenes via Ligand Relay Catalysis

Here,we report a cobalt-catalyzed sequential dehydrogenative Heck silylation/hydroamination of styrenes with hydrosilane and diazo compound to access 1-amino-2-silyl compounds with excellent regioselectivity.This difunctionalization reaction could undergo smoothly using 1 mol%catalyst loading with good functional group tolerance.Not only di-and tri-substituted hydrosilanes,but also alkoxysilane is suitable,which does explore the scope of the family of 1-amino-2-silyl compounds.The ligand relay phenomenon between neutral tridentate NNN ligand and anionic NNN ligand is observed for the first time via absorption spectral analysis in this one-pot,two-step transformations.The primary mechanism has been proposed based on the control experiments.

Recent Advances on the Electrochemical Difunctionalization of Alkenes/Alkynes

Electroorganic synthesis is an emerging area of high impact research in organic chemistry, which is considered as one of the green and efficient methods and attracts growing research attention. In this review, we summarized comprehensively the recent literature reports on the electrochemical oxidative difunctionalization of unsaturated C—C bonds. The reaction types described in this review included electrochemical intermolecular cyclization, electrochemical intramolecular cyclization, and electrochemical difunctionalization of alkenes/alkynes. This review focuses on the discussion of its synthetic generality for the preparation of functionalized compounds and the related electrochemical oxidative reaction mechanism.

Copper-catalyzed 1,1-difunctionalization of terminal alkynes: a three-component reaction for the construction of vinyl sulfones

A copper-catalyzed 1,1-difunctionalization of terminal alkynes was achieved via a three-component reaction, providing a variety of vinyl sulfones with good yields and excellent chemo-and stereoselectivity. Preliminary mechanistic studies indicated that the reaction probably underwent a Cu-catalyzed formal C–H insertion to produce an allene intermediate, which was then trapped by a sulfonyl anion to give the corresponding product.

Electrochemical synthesis of β-hydroxy-, β-alkoxy-, and β-carbonyloxy sulfones by vicinal difunctionalization of olefins

An electrochemical vicinal heterodifunctionalization of olefins for the synthesis ofβ-oxysulfones is described.With suitable choice of the conditions,including current,electrodes,and electrolyte,this oxidation reaction proceeded efficiently in an undivided cell without the use of a stoichiometric chemical oxidant.In addition to the previously established synthesis ofβ-hydroxysulfones in the presence of water,minor modification of this protocol by using either external alcohol nucleophiles or internal carboxylic acid nucleophile also led to the synthesis ofβ-alkoxysulfones,andβ-sulfonyl lactones.

Catalyst-controlled regiodivergent 1,2-difunctionalization of alkenes with two carbon-based electrophiles

Regiodivergent catalysis provides an efficient strategic approach for the construction of architecturally different molecules from the same starting materials. In this field, the intermolecular regiodivergent 1,2-difunctionalization of alkenes with two electrophiles is still a challenging task. A ligand-controlled, nickel-catalyzed regiodivergent dicarbofunctionalization of alkenes using both aryl/vinyl halides and acetals as electrophiles under mild reductive reaction conditions has been accomplished. This study provides a general approach to accessing both β-methoxyl esters and γ-methoxyl esters from readily available acrylates,aryl halides and acetals. Experimental mechanistic evidence supports that the difference in regioselective outcomes is attributed to the ligand tuning the reactivity of the nickel catalyst, which results in different catalytic cycles operating for these two reaction conditions.

Integrating aryl chlorides into nickel-catalyzed 1,1-difunctionalization of alkenes

Difunctionalization of alkenes have developed into an important type of reactions for rapidly and efficiently assemble complex molecules.While extensive advancements have been achieved by the assistance of transition metal catalysis,the employment of cheap,abundant aryl chlorides as coupling partner is still a challenging task in this field.Herein,we report our first achievement in 1,1-difunctionalization of alkenes with aryl chlorides as coupling partners.The success is predominantly ascribed to the judicious selection of 1,2-diamine ligand.This study provides an efficient protocol for the synthesis of secondary benzyl boronates from easily accessible feedstock chemicals.Furthermore,the distinguished features of this method include excellent 1,1-regio-and chemoselectivity,good functional group tolerance and easily-operational catalytic reaction conditions.

Recent advances in radical‐mediated transformations of 1,3‐dienes

1,3‐Dienes are a class of easily accessible and versatile feedstock chemicals that can participate in a wide range of reactions to facilitate the synthesis of various valuable allylic compounds.In the past decades,radical methodology has emerged as a powerful tool for organic synthesis by virtue of the fact that diverse highly reactive radical species can usually be generated under mild,neutral and controlled conditions,and allow for rapid generation of molecular complexity.In this review,we critically illustrate the recent advances in the field of radical‐mediated transformations of 1,3‐dienes based on the different radical precursors and working modes.Wherever possible,particular emphasis is also put on the related mechanistic studies and synthetic applications.

Iron phthalocyanine-catalyzed radical phosphinoylazidation of alkenes:A facile synthesis of β-azido-phosphine oxide with a fast azido transfer step

Phosphinoylazidation of alkenes is a direct method to build nitrogen-and phosphorus-containing compounds from feed-stock chemicals.Notwithstanding the advances in other phosphinyl radical related difunctionalization of alkenes,catalytic phosphinoylazidation of alkenes has not yet been reported.Here,we describe the first iron-catalyzed intermolecular phosphinoylazidation of styrenes and unactivated alkenes.The method is practically useful and requires a relatively low loading of catalyst.Mechanistic studies confirmed the radical nature of the reaction and disclosed the unusually low activation energy 4.8 kcal/mol of radical azido group transfer from the azidyl iron(III)phthalocyanine species(PcFeulN3)to a benzylic radical.This work may help to clarify the mechanism of iron-catalyzed azidation,inspire other mechanism studies and spur further synthetic applications.

Recent Advances in Enantioselective Reactions of Terminal Unactivated Alkenes

α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petro-chemical industry,and also found in natural products.Compared to the alkenes attaching the directing groups or activating group,the catalytic asymmetric reaction of unactivated terminal alkenes presents great challenges due to the weak electron effect and small steric hindrance effect.This review mainly summarizes the latest progress of the asymmetric reaction of unactivated terminal olefins since 2016.

Acylfluorination of enynes via phosphine and silver catalysis

This work describes intermolecular acylfluorination of gem-difluoroenynes using acyl fluorides as both acyl source and fluorine source.Trifluoromethyl-substituted allenones or furans could be selectively achieved via phosphine and silver catalysis.These approaches exhibit high regioselectivity,atom econ-omy and broad functionality tolerance.

Controlling the Reactivity of IBA-N_(3)by Switching Halogen Salts:Providing a Universal Strategy for Haloazidation of Alkenes

Although various routes have been reported for haloazidation,unavoidable problems exist,such as environmentally unfriendly monomer halogen,the need for in situ generation of unstable halogen azides(XN3),applicability to one type of haloazidation and inability to precisely control selectivity.Herein,we developed a universal strategy for haloazidation of alkenes through controlling the reactivity of IBA-N_(3) by switching halogen salts,allowing for the synthesis of a diversity of halogen azide products.Mechanistic studies have shown that by tuning the reactivity of IBA-N_(3) via switching halogen salts,different intermediates can be controllably produced to achieve regioselectivityand chemoselectivity in thehaloazidationof alkenes.

Synergistic Brønsted Base/Photoredox-Catalyzed Three-Component Coupling with Malonates to Synthesize δ-Hydroxy Esters and δ-Keto Esters

Multicomponent alkene 1,2-dicarbofunctionalizations(DCFs)have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C-C double bond in one step for enhancing molecular complexity and diversity.To the best of our knowledge,there is only one report on photoredox-catalyzed three-component DCFs with malonates through the radical−radical cross-coupling,while photoredox-catalyzed radical-polar crossover(RPC)-type DCFs with malonates were still rare.Herein,we describe a redox-neutral RPC-type 1,2-dialkylation of styrenes with malonates and aldehydes through the synergistic Brønsted base/photoredox catalysis system.This transition-metal-free strategy provides an efficient and clean approach to a broad variety ofδ-hydroxy esters and also features exceptionally mild conditions,wide compatibility of substrate scope and functional groups,and high atomic economy.Moreover,three-component 1,2-alkylacylation from the same starting materials was achieved in one-pot manner through such RPC-type coupling and subsequent two-electron oxidation process,providing a set ofδ-keto esters of interest in pharmaceutical research.

S-,P-stabilized bromoallenes for modular allenylborylation of alkenes

Simultaneously forming a carbon-carbon and a carbon-heteroatom bond in a single step through transition metal-catalyzed alkene difunctionalization strategy has emerged as a powerful tool for synthetic organic chemistry.Due to the uncontrollable reactivity,direct cross-coupling with bromoallenes as the building blocks for the selective allenation and borylation remains challenging.We herein report a new type of S-and P-stabilized bromoallenes for palladium-catalyzed modular allenation and borylation of alkenes to the divergent synthesis of multiply functionalized allenes in a highly regio-and diastereoselective manifold.The reaction features broad substrate scope and wide functional group compatibility,thus providing a straightforward method to install allenyl and boryl groups across alkenes.Control experiments highlight the crucial importance of S-,P-stabilization for the oxidative insertion of Pd-species into the allenyl-Br bond.The facile syntheses of bioactive allenic steroids and exocyclic allenes demonstrate the synthetic utility of this protocol.

Photocatalyzed ditrifluoromethylthiolation of alkenes with CF_(3)SO_(2)Na

Since the first report of sodium trifluoromethanesulfinate(CF_(3)SO_(2)Na) as an electrophilic trifluoromethylthiolation reagent in 2015,there has been no breakthrough in research in this field.Herein,we disclose an unprecedented usage of CF_(3)SO_(2)Na as a radical trifluoromethylthiolation reagent.A photocatalyzed ditrifluoromethylthiolation of alkenes with CF_(3)SO_(2)Na in the presence of PPh_(3) and catalytic copper has been developed.Interestingly,either Ir[(p-Fppy)_(2)(bpy)]PF_6 or Ir(ppy)_(3) could facilitate this transformation.Mechanistic studies indicate that initiation of the radical chain proceeded via two different photocatalytic quenching mechanisms.This protocol provides a practical method for the construction of diverse vicinal ditrifluoromethylthiolated compounds.

Nickel-Catalyzed Stereoselective Migratory Carboboration of 1,4-Cyclohexadiene

Multi-substituted cyclohexanes play a crucial role as scaffolds in bioactive compounds.While significant progress has been made in synthesizing substituted cyclohexanes,methods for the stereoselective assembly of 1,3-disubstituted cyclohexanes remain scarce.This study presents a novel approach involving nickel catalysis to achieve stereoselective carboboration of 1,4-cyclohexadiene.This innovative process allows for the simultaneous introduction of a boron group and an aryl or an alkyl fragment into the 1,4-cyclohexadiene framework under mild conditions,with exclusive regioselectivity and excellent cis configuration.The resulting products feature a double carbon bond and the incorporation of the boron group,offering significant potential for subsequent transformations and downstream applications.

Catalytically generated noncovalent ammonium dienolate:a versatile platform for the development of organocatalytic asymmetric cascade reactions

Organocatalytic cascade reactions represent a powerful strategy for the rapid construction of complex chiral molecules with multiple stereocenters from simple substrates under mild conditions. The intriguing structural feature and diverse reactivity of catalytically generated dienolate species render them competent and versatile intermediates for the development of practical and valuable cascade reactions. Over the past years, a plethora of innovative and pioneering noncovalent ammonium dienolatemediated cascade reactions have been designed and implemented under the catalysis of chiral organocatalysts, making dienolate activation a general, robust, and complementary method for the functionalization of unsaturated carbonyl compounds and related substances. This review illustrates the recent advances in organocatalytic noncovalent ammonium dienolate-mediated cascade reactions(mainly from 2010 to 2023), including the cascade transformations of ammonium dienolates directly generated from unsaturated ketone/aldehyde, ester/lactone/azlactone, amide/lactam/pyrazolone/oxindole, and alkylidene nitrile compounds. The contents are arranged based on the reaction types of the ammonium dienolates, with an emphasis on cascade 2,5-, 3,5-, and 4,5-difunctionalizations of these intermediates. Furthermore, other cascade reactions involving the 1,3-, 2,3-, and even more complex 3,4,5-reactivities of ammonium dienolates were also discussed. The reaction pathway, reaction stereoinduction, and synthetic applications of the ammonium dienolate-mediated cascade reactions were highlighted throughout the article. As a stimulating and ever-growing research area, the organocatalytic noncovalent ammonium dienolate-mediated cascade reactions are expected to continue demonstrating their magic power for constructing chiral targets in the future and further expanding the boundaries of asymmetric catalysis.

Controllable Construction of Vinyl Sulfones and β-Keto Selenosulfones via Selective Oxidative Sulfonylation of Alkenes

Comprehensive Summary The selective oxidative sulfonylation of alkenes with selenium sulfonate depended on the reaction conditions.The electrochemical C—H sulfonylation proceeded smoothly to afford(E)-vinyl sulfones with good selectivity in an undivided cell without external oxidant.While aerobic trifunctionalization of alkenes occurred in the presence of KI in the air,which providesβ-keto selenosulfones via the formation of C—O,C—S,and C—Se bonds in one-pot.Following control experiments,a plausible mechanism is proposed to rationalize the experimental results.