Radical Fluorosulfonamidation: A Facile Access to Sulfamoyl Fluorides.

Recently, the introduction of fluorosulfonyl (-SO2F) groups have attracted considerable research interests, as this moiety could often afford enhanced activities and new functions in the context of chemical biology and drug discovery. Herein, we report the design and synthesis of 1-fluorosulfamoyl-pyridinium (FSAP) salts, which could serve as an effective photoredox-active precursor to fluorosulfamoyl radicals and enable the direct radical C-H fluorosulfonamidation of a variety of (hetero)arenes. This method features mild conditions, visible light, broad substrate scope, good group tolerance, etc., and a metal-free protocol is also viable by using organic photocatalysts. Further, FSAP can also be applied to the radical functionalization of alkenes via 1,2-difunctionalization, radical distal migration, tandem radical-polar crossover reactions, etc. In addition, a formal C-H methylamination of (hetero)arenes by combining this radical C-H fluorosulfonamidation with subsequent hydrolysis as well as product derivatization are also demonstrated.

Radical Ring-Opening Fluorosulfonylation of Methylenecyclobutanols via Electron Donor-Acceptor Photoactivation.

A visible-light-mediated catalyst- and additive-free method for radical ring-opening fluorosulfonylation of methylenecyclobutanols is reported. Sulfuryl chlorofluoride acts as a FSO2 radical precursor as well as an electron acceptor to form electron donor-acceptor complexes with various methylenecyclobutanol substrates. This method shows fully regioselective and (E)-stereoselective ring-opening processes, providing a variety of FSO2-functionalized γ,δ-unsaturated carbonyls in 38-77% yields. A selection of product diversifications has been studied to demonstrate the versatility of these sulfonyl fluoride products.

The Development of Visible-Light Organic Photocatalysts for Atom Transfer Radical Polymerization via Conjugation Extension.

This work aimed to develop organic photocatalysts (PCs) that could mediate organocatalytic atom transfer radical polymerization (O-ATRP) under visible light. Through the core-modification of known chromophoric structures and ring-locking to reach a conjugation extension, annulated N-aryl benzo[kl]acridines were identified as effective visible light-responsive photocatalysts. The corresponding selenium-doped structure showed excellent performance in the O-ATRP of methacrylates, which could afford polymer products with controlled molecular weights and low dispersities under the irradiation of visible light at a 100 ppm catalyst loading.

Fluorosulfonyl Arylation of Alkynes via Electron Donor-Acceptor Photoactivation.

A radical fluorosulfonyl arylation of alkynes with sulfuryl chlorofluoride as the FSO2 radical precursor via electron donor-acceptor photoactivation driven by daylight or a blue light-emitting diode is disclosed. A series of valuable benzo-fused carbocycles and heterocycles have been produced with simple operation under mild conditions in the absence of any external catalysts or additives. The synthetic potential of this protocol has further demonstrated excellent scalability, as well as diverse postderivatizations, including SuFEx reactions and other useful cascade reactions.

Visible Light-Regulated Ring-Opening Polymerization of Lactones by Employing Indigo as a Photoacid Catalyst.

The development of visible light-regulated polymerizations for precision synthesis of polymers has drawn considerable attention in the past years. In this study, an ancient dye, indigo, is successfully identified as a new and efficient photoacid catalyst, which can readily promote the ring-opening polymerization of lactones under visible light irradiation in a well-controlled manner, affording the desired polyester products with predictable molecular weights and narrow dispersity. The enhanced acidity of indigos by excitation is crucial to the H-bonding activation of the lactone monomers. Chain extension and block copolymer synthesis are also demonstrated with this method.

Asymmetric Ion-Pairing Photoredox Catalysis for Stereoselective Cationic Polymerization under Light Control.

By virtue of noninvasive regulations by light, photocontrolled polymerizations have attracted considerable attention for the precision synthesis of macromolecules. However, a cationic polymerization with simultaneous photocontrol and tacticity-regulation remains elusive so far. Herein, we introduce an asymmetric ion-pairing photoredox catalysis strategy that allows for the development of a stereoselective cationic polymerization with concurrent light regulation for the first time. By employing an ion pair catalyst (PC+/*A-) consisting of a photoredox active cation (PC+) and a sterically confined chiral anion (*A-) to deliver the stereochemical control, the cationic polymerization of vinyl ethers can be achieved with photocontrol and high isotactic selectivity (up to 91% m) at a remarkable low catalyst loading (50 ppm).

Radical Hydro-Fluorosulfonylation of Propargylic Alcohols via Electron Donor-Acceptor Photoactivation.

A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation of the electron donor-acceptor (EDA) complex. The reaction avoids the requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling the facile synthesis of various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to various privileged molecules of biological relevance.

Electroreductive hydroxy fluorosulfonylation of alkenes.

An electroreductive strategy for radical hydroxyl fluorosulfonylation of alkenes with sulfuryl chlorofluoride and molecular oxygen from air is described. This mild protocol displays excellent functional group compatibility, broad scope, and good scalability, providing convenient access to diverse ß-hydroxy sulfonyl fluorides. These ß-hydroxy sulfonyl fluoride products can be further converted to valuable aliphatic sulfonyl fluorides, ß-keto sulfonyl fluorides, and ß-alkenyl sulfonyl fluorides. Further, some of these products showed excellent inhibitory activity against Botrytis cinerea or Bursaphelenchus xylophilus, which could be useful for potent agrochemical discovery. Preliminary mechanistic studies indicate that this transformation is achieved through rapid O2 interception by the alkyl radical and subsequent reduction of the peroxy radical, which outcompete other side reactions such as chlorine atom transfer, hydrogen atom transfer, and Russell fragmentation.

FSO2 Radical-Initiated Tandem Addition Reaction of Two Different Olefins: A Facile Access to Multifunctional Aliphatic Sulfonyl Fluorides.

Multicomponent reactions represent a powerful method for building complex molecules from structurally simple starting materials. Herein, we report a novel three-component radical-polar crossover reaction involving a tandem addition reaction of two different olefins, which is initiated by the selective addition of fluorosulfonyl radicals to alkyl alkenes. This tandem process provides facile and effective access to multiple functionalized aliphatic sulfonyl fluoride molecules. Further transformation of the products is also demonstrated.

Fluorosulfonylvinylation of Unactivated C(sp3)-H via Electron Donor-Acceptor Photoactivation.

An electron donor-acceptor (EDA) complex photoactivation strategy for radical fluorosulfonylation is disclosed for the first time. Simply upon blue light irradiation, the FSO2 radical can be generated efficiently under catalyst-free, base-free, and additive-free conditions, which enables facile access to 6-keto alkenylsulfonyl fluorides from readily available propargyl alcohols and FSO2Cl. The 6-keto alkenylsulfonyl fluoride motif has been showcased as a versatile SuFEx hub with diverse follow-up derivatizations.

Radical Fluorosulfonyl Heteroarylation of Unactivated Alkenes with Quinoxalin-2(1H)-ones and Related N-Heterocycles.

The incorporation of sulfonyl fluoride groups into molecules has been proved effective to enhance their biological activities or introduce new functions. Herein, we report a transition-metal-free and visible-light-mediated radical 1-fluorosulfonyl-2-heteroarylation of alkenes, which could allow access to a series of SO2F-containing quinoxalin-2(1H)-ones, which are a critical structural motif widely present in a number of biologically active molecules. Further application of the method to the modification of other heterocycles and drug molecules as well as ligation chemistry via SuFEx click reactions is also demonstrated.

Organocatalytic [2 + 2] Photopolymerization under Visible Light: Accessing Sustainable Polymers from Cinnamic Acids.

Herein, the successful development of a metal-free, solution [2 + 2] photopolymerization of natural cinnamic acid-derived bisolefinic monomers is reported, which is enabled by a strategy based on direct triplet state access via energy transfer catalysis. 2,2'-Methoxythioxanthone has been identified as an effective organic photocatalyst for the [2 + 2] photopolymerization in solution, which can be excited by visible light and activate the biscinnamate monomers via triplet energy transfer. This method features its metal-free conditions, visible light utilization, solution polymerization, and abundant biomass-based feedstock, as well as processable polymer products, which is different from the rigid, insoluble products obtained from solid-state photopolymerization. This solution polymerization method also shows a good compatibility to monomer structures; cinnamic acid-derived bisolefinic monomers with different linkers, including diamine, natural diol, and bisphenol, can all readily undergo [2 + 2] photopolymerization, and be transformed into colorless, sustainable polymers.

Organocatalytic Ring-Opening Polymerization of ϵ-Caprolactone with Phosphoramidimidates (PADIs) as a Bifunctional Brønsted Acid Catalyst.

In this study, an organocatalytic ring-opening polymerization (ROP) of ϵ-caprolactone (ϵ-CL) has been developed by employing PADIs as a novel and efficient acid/base bifunctional organocatalyst, which could afford metal-free poly(ϵ-caprolactone) with predictable molecular weight and narrow dispersity at a low catalyst loading under mild conditions. NMR and kinetic studies indicate that the ring-opening polymerizations of lactones catalyzed by PADIs proceed in a living and well controlled manner. Moreover, this organic Brønsted acid catalytic system could allow the synthesis of PCL with molecular weight above 60 kg/mol, as well as well-defined star polymers.

Linear Cyclobutane-Containing Polymer Synthesis via [2 + 2] Photopolymerization in an Unconfined Environment under Visible Light.

The [2 + 2] photopolymerization of diolefinic monomers is an appealing approach for the construction of polymeric materials. Herein, we demonstrate that the establishment of an effective donor-acceptor conjugation by introducing electron-donating alkoxy groups at appropriate positions of the benzene ring could activate p-phenylenediacrylate (PDA), thus enabling the development of the first solution [2 + 2] photopolymerization of such monomers under the irradiation of visible light. Variation on the alkoxy groups and the ester parts could allow access to a series of linear cyclobutane-containing polymer products with high molecular weight (up to 140 kDa) and good solubility in common solvents. Further, temporal control and postpolymerization modification with preinstalled pendant C═C bonds via thiol-ene click reaction are also demonstrated with this [2 + 2] photopolymerization system.

Radical Fluorosulfonyl Arylation of Alkenes: Accessing FSO2-Functionalized Chromanes via Formal Endo and Exo Cyclization.

The introduction of sulfonyl fluoride groups into bioactive molecules can often bring about enhanced biological activity, which has attracted more research interest in chemical biology and drug development in recent years. Here, we report the development of a radical fluorosulfonylation of alkenes/intramolecular arylation cascade for the construction of chromanes with sulfonyl fluoride groups attached. The radical 1,2-fluorosulfonyl arylation reactions proceed well in both endo and exo cyclization fashions, allowing for further variation of the distance between the chromane core and the sulfonyl fluoride group.

Radical Hydro-Fluorosulfonylation of Unactivated Alkenes and Alkynes.

Recently, radical fluorosulfonylation is emerging as an appealing approach for the synthesis of sulfonyl fluorides, which are highly in demand in various disciplines, particularly in chemical biology and drug discovery. Here, we report the first establishment of radical hydro-fluorosulfonylation of alkenes, which is enabled by using 1-fluorosulfonyl 2-aryl benzoimidazolium (FABI) as an effective redox-active radical precursor. This method provides a new and facile approach for the synthesis of aliphatic sulfonyl fluorides from unactivated alkenes, and can be further applied to the late-stage modifications of natural products and peptides, as well as ligation of drugs in combination with click chemistry. Remarkably, this system could enable the radical hydro-fluorosulfonylation of alkynes, affording valuable alkenylsulfonyl fluoride products with a rare, high Z-selectivity, which are normally less stable and more challenging to synthesize in comparison with the E-configured products.

Monophosphoniums as Effective Photoredox Organocatalysts for Visible Light-Regulated Cationic RAFT Polymerization.

Visible light-regulated metal-free polymerizations have attracted considerable attention for macromolecular syntheses in recent years. However, few organic photocatalysts show high efficiency and strict photocontrol in cationic polymerizations. Herein, we introduce monophosphonium-doped polycyclic arenes as an organic photocatalyst, which features the high tunability, broad redox window, long excited state lifetime, and excellent temporal control in the cationic reversible addition-fragmentation chain transfer polymerization of vinyl ethers. A correlation of the catalytic performance and the photophysical and electrochemical properties of photocatalysts is also discussed.

Photoredox catalytic radical fluorosulfonylation of olefins enabled by a bench-stable redox-active fluorosulfonyl radical precursor.

Sulfonyl fluorides have attracted considerable and growing research interests from various disciplines, which raises a high demand for novel and effective methods to access this class of compounds. Radical flurosulfonylation is recently emerging as a promising approach for the synthesis of sulfonyl fluorides. However, the scope of applicable substrate and reaction types are severely restricted by limited known radical reagents. Here, we introduce a solid state, redox-active type of fluorosulfonyl radical reagents, 1-fluorosulfonyl 2-aryl benzoimidazolium triflate (FABI) salts, which enable the radical fluorosulfonylation of olefins under photoredox conditions. In comparison with the known radical precursor, gaseous FSO2Cl, FABI salts are bench-stable, easy to handle, affording high yields in the radical fluorosulfonylation of olefins with before challenging substrates. The advantage of FABIs is further demonstrated in the development of an alkoxyl-fluorosulfonyl difunctionalization reaction of olefins, which forges a facile access to useful ß-alkoxyl sulfonyl fluorides and related compounds, and would thus benefit the related study in the context of chemical biology and drug discovery in the future.

Electrochemical Synthesis of ß-Keto Sulfonyl Fluorides via Radical Fluorosulfonylation of Vinyl Triflates.

Electrochemical synthesis of versatile ß-keto sulfonyl fluorides is accomplished by radical fluorosulfonylation of vinyl triflates with FSO2Cl as the fluorosulfonyl radical source. This electroreductive protocol uses inexpensive graphite felt as electrodes, thus avoiding the use of a sacrificial anode. Moreover, this protocol, featuring metal-free, mild conditions and easy scalability, allows expedient access to valuable ß-keto sulfonyl fluorides from readily available precursors, as well as the cyclic ones that are otherwise inaccessible using prior methods.

Organocatalytic, Stereoselective, Cationic Reversible Addition-Fragmentation Chain-Transfer Polymerization of Vinyl Ethers.

Tacticity is a crucial factor affecting the properties of synthetic polymer materials. Here, we introduce a type of chiral organic Brønsted acid catalyst, 1,1'-bi-2-naphthol-derived N,N'-bis(triflyl)phosphoramidimidates (PADIs), for the cationic polymerization of vinyl ethers, which enables the development of the first organocatalytic, highly stereoselective, cationic reversible addition-fragmentation chain-transfer (RAFT) polymerization of vinyl ethers with a trithiocarbonate chain-transfer agent. This metal-free RAFT process could afford isotactic poly(vinyl ethers) with high stereoselectivity, controllable molecular mass, and narrow dispersity at low catalyst loadings (as low as 200 ppm). Moreover, the trithiocarbonate chain-end allows for chain extension to synthesize diblock copolymers comprising an isotactic poly(vinyl ether) block, by a mechanistic switching from stereoselective cationic RAFT polymerization to visible-light-regulated cationic and radical RAFT polymerization.