Pyridinium-Based Fluorosulfonamide Reagents Enabled Photoredox-Catalyzed Radical Fluorosulfonamidation.

Sulfamoyl fluorides, as a crucial building block of SuFEx, have garnered extensive research interest due to their unique properties. However, the direct radical fluorosulfonamidation process for the synthesis of sulfamoyl fluorides has been overlooked. We herein disclosed a practical procedure for constructing a redox-active fluorosulfonamide radical reagent named fluorosulfonyl-N-pyridinium tetrafluoroborate (PNSF) from SO2F2. These reagents can facilitate a range of reactions, including the N-(fluorosulfonyl) sulfonamidation of (hetero)arenes, sequential radical stereoselective fluorosulfonamidation, and 1,2-difunctionalization of alkenes.

Photoredox-catalyzed stereo- and regioselective vicinal fluorosulfonyl-borylation of unsaturated hydrocarbons.

There has been considerable research on sulfur(vi) fluoride exchange (SuFEx) chemistry, which is considered to be a next-generation click reaction, and relies on the unique balance between reactivity and stability inherent in high valent organosulfur. The synthetic versatility of the bifunctional handles containing the fluorosulfonyl group presents great synthetic value and opportunity for drug discovery. However, the direct photoredox-catalyzed fluorosulfonyl-borylation process remains unexplored and challenging due to its system incompatibility and limited synthetic strategies. Herein, we developed a sequential photocatalytic radical difunctionalization strategy for the highly efficient stereoselective synthesis of vicinal fluorosulfonyl borides (VFSBs) with an integrated redox-active SO2F radical reagent. The VFSBs acted as orthogonal synthons, and were subjected to a range of convenient transformations via the cleavage of the C-B and S(vi)-F bonds, including halogenation, Suzuki coupling, hydrogenation, and the SuFEX click reaction, which demonstrated the great potential of the VFSB moieties for use in skeleton linkage and drug modification.

A photoinduced transient activating strategy for late-stage chemoselective C(sp3)-H trifluoromethylation of azines.

The direct functionalization of C(sp3)-H bonds is an ultimately ideal synthetic strategy with high atom economy and step efficiency. However, the direct trifluoromethylation of electron-deficient heteroaryl adjacent C(sp3)-H bonds remains a formidable challenge. We have described a transient activating strategy involving a Tf-shift process and π-π stacking interaction for catalyst-free direct benzylic C(sp3)-H trifluoromethylation of azines, such as pyridine, pyrimidine, quinoline, dihydropyridinone, tetrahydroisoquinoline and tetrahydroquinazoline, with an air-stable crystalline imidazolium sulfonate reagent IMDN-Tf. This bench-stable cationic reagent offers a scalable and practical protocol for the late-stage modification of drug molecules with high site selectivity, which avoids the prefunctionalization and the use of stoichiometric metals and strong oxidants. Furthermore, comprehensive mechanistic studies revealed the determining effect of π-π stacking for the activation of azinylic C(sp3)-H bonds.

A practical fluorosulfonylating platform via photocatalytic imidazolium-based SO2F radical reagent.

Sulfonyl fluorides are key components in the fields of chemical biology, materials science and drug discovery. In this line, the highly active SO2F radical has been employed for the construction of sulfonyl fluorides, but the utilization of gaseous ClSO2F as radical precursor is limited due to the tedious and hazardous preparation. Meanwhile, the synthesis of sulfonyl fluorides from inert SO2F2 gas through a fluorosulfonyl radical (·SO2F) process has met with inevitable difficulties due to the high homolytic bond dissociation energy of the S(VI)-F bond. Here we report a radical fluorosulfonylation strategy for the stereoselective synthesis of alkenyl sulfonyl fluorides and functional alkyl sulfonyl fluorides with an air-stable crystalline benzimidazolium fluorosulfonate cationic salt reagent. This bench-stable redox-active reagent offers a useful and operational protocol for the radical fluorosulfonylation of unsaturated hydrocarbons with good yield and high stereoselectivity, which can be further transformed into valuable functional SO2F moieties.

Electrochemical-Promoted Nickel-Catalyzed Oxidative Fluoroalkylation of Aryl Iodides.

This work describes a general strategy for metal-catalyzed cross-coupling of fluoroalkyl radicals with aryl halides under electrochemical conditions. The contradiction between anodic oxidation of fluoroalkyl sulfinates and cathodic reduction of low-valent nickel catalysts can be well addressed by paired electrolysis, allowing for direct introduction of fluorinated functionalities into aromatic systems.

Integrated redox-active reagents for photoinduced regio- and stereoselective fluorocarboborylation.

Vinylboronates and alkylboronates are key components in variegated transformations in all facets of chemical science. The synthesis of vinylboronates and alkylboronates suffers from step-tedious and poor stereoselective procedures. We have developed a regulated radical difunctionalization strategy for the construction of fluorine-containing vinylboronates and alkylboronates with an integrated redox-active reagent IMDN-SO2RF. This bench-stable imidazolium sulfonate cationic salt offers a scalable and operational protocol for the fluoroalkylation-borylation of unsaturated hydrocarbons in a high regio- and stereoselective manner. The products can be further transformed into valuable fluorinated building blocks.

Redox-active benzimidazolium sulfonamides as cationic thiolating reagents for reductive cross-coupling of organic halides.

Redox-active benzimidazolium sulfonamides as thiolating reagents have been developed for reductive C-S bond coupling. The IMDN-SO2R reagent provides a bench-stable cationic precursor to generate a portfolio of highly active N-S intermediates, which can be successfully applied in cross-electrophilic coupling with various organic halides. The employment of an electrophilic sulfur source solved the problem of catalyst deactivation and avoided odorous thiols, featuring practical conditions, broad substrate scope, and excellent tolerance.

Electrochemically Promoted Fluoroalkylation-Distal Functionalization of Unactivated Alkenes.

Difunctionalization of olefins represents a powerful synthetic tool and yet a challenging task. This work describes an electrochemically enabled fluoroalkylation-migration reaction of unactivated olefins in the absence of a strong oxidant or heavy metal catalyst, affording fluorinated (hetero)aryl ketones in good yields and excellent regioselectivities. The efficient and sustainable electrochemical strategy provides a rapid access to a dual functionalized fluorine-containing heterocyclic manifold.

Leaving Group Assisted Strategy for Photoinduced Fluoroalkylations Using N-Hydroxybenzimidoyl Chloride Esters.

Redox-active esters (RAEs) as alkyl radical precursors have been extensively developed for C-C bond formations. However, the analogous transformations of fluoroalkyl radicals from the corresponding acid or ester precursors remain challenging because of the high oxidation potential of the fluoroalkyl carboxylate anions. The newly developed N-hydroxybenzimidoylchloride (NHBC) ester provides a general leaving group assisted strategy to generate a portfolio of fluoroalkyl radicals, and can be successfully applied in photoinduced decarboxylative hydrofluoroalkylation and heteroarylation of unactivated olefins. In addition, DFT calculations revealed that the NHBC ester proceeds by the fluorocarbon radical pathway, whereas other well-known RAEs proceed by the nitrogen radical pathway.