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Electrosynthesis has received great attention among researchers in both academia and industry as an ideal technique to promote single electron reduction without the use of expensive catalysts. In this work, we report the electrochemical reduction of Katritzky salts to alkyl radicals by sacrificing the easily accessible metal anode. This catalyst and electrolyte free platform has broad applicability to single electron transfer chemistry, including fluoroalkenylation, alkynylation and thiolation. The deaminative functionalization is facilitated by the rapid molecular diffusion across microfluidic channels, demonstrating the practicality that outpaces the conventional electrochemistry setups., Electrochemical transformations use electrons and electron holes instead of chemical oxidants and reductants as reagents. Here, the authors report an electrochemical reductive deaminative cross-coupling of Katrizky salts with various radical acceptors, including examples of fluoroalkenylation, alkynylation and thiolation.

A photoinduced 1,4-heteroaryl migration from a carbon center to a nitrogen center accompanied by a cyanoalkylacylation of heterocyclic-substituted azidyl homoallylic alcohols and cycloketone oxime esters has been described. This simple and powerful protocol merged the dual C–C bond cleavage with C–N bond formation, providing an efficient and environmentally safe approach to a variety of synthetically useful cyanoalkyl-containing β-enamino ketones with outstanding selectivity and commendable functional group compatibility. Moreover, the application of microflow technique enhanced these reactions compared with the equivalent batch reaction, significantly reducing the reaction times to 5–9.3 min and broadening the substrate scope to more than 35 successful substrates.

Here we developed a novel method involving the use of continuous flow for the selective alkynylation of cysteine-containing peptides and 1-thioglycoside residues. This method was characterised by mild conditions (room temperature, metal-free, oxidant-free conditions), greatly enhancing its usefulness for modifying amino acids and peptides. The newly developed S-alkynylation reagents could apparently reduce the cost and difficulty of the synthesis, thus increasing the sustainability and economy of the process. Moreover, good to excellent yields were obtained for a selection of alkynylated cysteine-containing peptides (35 examples) and 1-thioglycoside residues (15 examples) within short residence times (3–4 minutes).

Currently, the selective activation of C(sp3)–F bonds and C–C bonds constitute one of the most widely used procedures for the synthesis of high-value products that range from pharmaceuticals to agrochemical applications. While numerous examples of these two methods have been reported in their respective fields, the processes which merge the activation of both single C(sp3)-F bonds and C–C bonds in one step still remain elusive. Here, we demonstrate the controllable defluoroalkylation–distal functionalization of trifluoromethylarenes with unactivated alkenes via distal heteroaryl migration. This is proposed to proceed via tandem C(sp3)–F and C–C bond cleavage using visible-light photoredox catalysis combined with Lewis acid activation. This strategy provides facile and flexible access to multiply functionalized α,α-difluorobenzylic ketones in useful yields (up to 88%) under mild conditions. The products can be further transformed into other valuable compounds, demonstrating the method’s utility. The radical C–F cleavage of fluoroalkanes offers a valuable method for the synthesis of fluorinated products. Here, photoredox catalysis promotes tandem intermolecular defluoroalkylation/intramolecular heteroaryl migration of unactivated alkenes to yield difluorobenzyl ketones, proposed to proceed via a radical mechanism.

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri- and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri- or difluoromethylated 2-(2-acetylphenyl)isoquinoline-1,3-diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N-substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant-free conditions.

A direct electrooxidative sulfonylation/heteroarylation reaction of alkenes with sulfinic acids, which proceeds through distal heteroaryl ipso-migration and C-S and C-C bond formations, is reported. This electro-synthetic method offers an efficient and environmentally friendly entry to prepare various sulfonated functionalized heteroarenes under an undivided cell at room temperature, avoiding the use of any metal catalysts, additives, and oxidants. Preliminary mechanistic studies indicated a radical pathway.

A novel three-component selenosulfonation of 1,7-enynes with sulfinic acids and diphenyl diselenides for the formation of multifunctional 3,4-dihydroquinolin-2(1H)-ones was developed in batch and flow. This room-temperature protocol provides a highly efficient approach to diverse selenosulfones in moderate to excellent yields and with a broad scope of substrates. It should provide a potential synthesis method for the construction of diverse and meaningful 3,4-dihydroquinolin-2(1H)-ones derivatives in the fields of pharmaceutical and biological chemistry. Additionally, obvious acceleration (20h to 43s) was obtained under micro flow conditions.

Silver-mediated C(sp3)–H functionalization and 6-endo-dig oxo-cyclization of conjugated β-alkynyl ketones have been established under oxidative conditions. The reaction leads to the concise formation of a wide range of isochromenes via C(sp3)–H bond-breaking and radical addition steps. Dual and monofunctional isochromene products were selectively controlled by using either electron-rich or electron-deficient radical sources.

A metal-free arylsulfonyl radical-triggered desulfonylation of N-aryl-N-arylsulfonyl-acrylamides under mild conditions for the facile synthesis of a series of sulfonylated amides has been described. The radical transformation simultaneously installs C–S and C–C bonds with concomitant cleavage of N–S and C–S bonds through continuous 5-exo-trig cyclization, desulfonylation, and aryl migration sequence.

New I2-catalyzed multicomponent bicyclization reactions of β-ketonitriles with sulfonyl hydrazides have been established, providing a direct and metal-free access toward unreported pyrazolo[1,5-a]pyrimidin-4-ium sulfonates. The latter could be quantitatively converted into densely functionalized pyrazolo[1,5-a]pyrimidines in the presence of bases. Using sulfonyl hydrazides as a sulfenylating agent, the resulting pyrazolo[1,5-a]pyrimidines enabled I2-catalyzed unprecedented disulphenylations to access fully substituted pyrazolo[1,5-a]pyrimidines through direct C(sp(2))-H bond bifunctionalization.

A new base-promoted bicyclization strategy for the synthesis of functionalized indeno[1,2-b]pyran-2-ones has been established from readily accessible o-phthalaldehydes (OPA) and the preformed 1-arylethylidenemalononitriles. The reaction pathway involves an aldol addition, 5-exo-trig carbocyclization and 6-exo-dig oxo-cyclization sequence, resulting in continuous multiple C–C and C–O bond formation.

A new metal-free bicyclization reaction of 1,7-enynes anchored by α,β-conjugates with arylsulfonyl radicals generated in situ from sulfonyl hydrazides has been established using tert-butyl hydroperoxide and tetrabutylammonium iodide. The reactions occurred through sulfonylation/6-exo-dig/6-exo-trig bicyclization/in situ desulfonylation/5-exo-trig cyclization/alkyl or alkenyl migration cascade mechanism to give benzo[j]phenanthridines regioselectively.

A catalytic domino spirocyclization of 1,7-enynes with simple cycloalkanes and cyclo-1,3-dicarbonyls has been established via multiple C-C bond formations from alkynyl/alkenyl functions and dual α,α-C(sp(3))-H abstraction/insertion. The reaction involves addition, 6-exo-dig cyclization and radical coupling sequences under convenient catalytic conditions and provides a concise access to spiro cyclopenta[c]quinolines in good to excellent yields.

A base-promoted [3 + 2] cycloaddition for the construction of multi-functionalized imidazo[1,2-a]indole derivatives with good yields has been accomplished. This transformation provides an easy and facile protocol for the formation of diverse imidazo[1,2-a]indoles of chemical and biomedical importance using preformed 3-sulfonyl-2-sulfonyldiazenyl-1H-indoles and readily available but-2-ynedioates under mild conditions.

A novel chemoselective polymerization methodology was established by employing rare earth catalysis and microflow technology. The microscale effect (inner size and flow rate) on chemoselectivity and polymerization kinetic were investigated for the model system of mercapto-alcohol initiating ring-opening polymerizations (ROP) of caprolactone (e-CL) in the presence of lanthanum tris(2,6-di-tert-butyl-4-methylphenolate)s. By reducing the inner diameter (ID) of the microreactor tube from 4 mm to 0.5 mm, the chemoselectivity (thiol fidelity) was firstly increased from 63% into 74% and then decreased to 69%. Faster flow rates enabled better chemoselective (82% at 667 μL min−1 vs 63% at 167 μL min−1). The chemoselective polymerization kinetics were compared between batch reactor and microreactor with varied ID. In contrast to the batchwise reaction, flow chemistry brought great benefits in the chemoselective polymerization, including faster polymerization, higher thiol fidelity, more controlled molecular weight and distributions. Microreactor with 2 mm ID showed better performance than that with 1 mm ID, which was consistent with the results of microscale effect study. Six varied rare earth phenolates were utilized to demonstrate the versatility of microflow system and resultant polymer exhibited thiol fidelity over 87%. By applying this continuous flow chemoselective ROP strategy, series of well-defined thiol-terminated poly poly(e-caprolactone)s were efficiently synthesized under optimized flow conditions with high thiol fidelity (>91%) and varied molecular weights (3440–15,090 g mol−1). This work would provide deep insight into microflow technology and chemoselective polymerization.

A new base-promoted bicyclization strategy for the synthesis of functionalized indeno[1,2-b]pyran-2-ones has been established from readily accessible o-phthalaldehydes (OPA) and the preformed 1-arylethylidenemalononitriles. The reaction pathway involves an aldol addition, 5-exo-trig carbocyclization and 6-exo-dig oxo-cyclization sequence, resulting in continuous multiple C–C and C–O bond formation.

A metal-free arylsulfonyl radical-triggered desulfonylation of N-aryl-N-arylsulfonyl-acrylamides under mild conditions for the facile synthesis of a series of sulfonylated amides has been described. The radical transformation simultaneously installs C–S and C–C bonds with concomitant cleavage of N–S and C–S bonds through continuous 5-exo-trig cyclization, desulfonylation, and aryl migration sequence.

New I2-catalyzed multicomponent bicyclization reactions of β-ketonitriles with sulfonyl hydrazides have been established, providing a direct and metal-free access toward unreported pyrazolo[1,5-a]pyrimidin-4-ium sulfonates. The latter could be quantitatively converted into densely functionalized pyrazolo[1,5-a]pyrimidines in the presence of bases. Using sulfonyl hydrazides as a sulfenylating agent, the resulting pyrazolo[1,5-a]pyrimidines enabled I2-catalyzed unprecedented disulphenylations to access fully substituted pyrazolo[1,5-a]pyrimidines through direct C(sp2)–H bond bifunctionalization.

A new metal-free oxidative hydrophosphinylation of 1,7-enynes for forming polyfunctionalized 3,4-dihydroquinolin-2(1H)-ones has been realized using readily accessible diarylphosphine oxide and TBPB as an oxidant. The reaction pathway involves an in situ-generated P-centered radical-triggered α,β-conjugate addition/6-exo-dig cyclization/H-abstraction sequence, providing a direct and promising protocol for the formation of C–P, C–C and C–H bonds and rapid construction of complex heterocyclic compounds.

A new cascade three-component halosulfonylation of 1,7-enynes for efficient synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones has been established from readily accessible arylsulfonyl hydrazides and NIS (or NBS). The reaction pathway involves in situ-generated sulfonyl radical-triggered α,β-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in continuous multiple bond-forming events including C-S, C-C and C-I (or C-Br) bonds to rapidly build up molecular complexity.

A new metal-free bicyclization reaction of 1,7-enynes anchored by α,β-conjugates with arylsulfonyl radicals generated in situ from sulfonyl hydrazides has been established using tert-butyl hydroperoxide and tetrabutylammonium iodide. The reactions occurred through sulfonylation/6-exo-dig/6-exo-trig bicyclization/in situ desulfonylation/5-exo-trig cyclization/alkyl or alkenyl migration cascade mechanism to give benzo[j]phenanthridines regioselectively.

A catalytic domino spirocyclization of 1,7-enynes with simple cycloalkanes and cyclo-1,3-dicarbonyls has been established via multiple C–C bond formations from alkynyl/alkenyl functions and dual α,α-C(sp3)-H abstraction/insertion. The reaction involves addition, 6-exo-dig cyclization and radical coupling sequences under convenient catalytic conditions and provides a concise access to spiro cyclopenta[c]quinolines in good to excellent yields.

A base-promoted [3 + 2] cycloaddition for the construction of multi-functionalized imidazo[1,2-a]indole derivatives with good yields has been accomplished. This transformation provides an easy and facile protocol for the formation of diverse imidazo[1,2-a]indoles of chemical and biomedical importance using preformed 3-sulfonyl-2-sulfonyldiazenyl-1H-indoles and readily available but-2-ynedioates under mild conditions.

A new cascade three-component halosulfonylation of 1,7-enynes for efficient synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones has been established from readily accessible arylsulfonyl hydrazides and NIS (or NBS). The reaction pathway involves in situ-generated sulfonyl radical-triggered α,β-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in continuous multiple bond-forming events including C-S, C-C and C-I (or C-Br) bonds to rapidly build up molecular complexity.

A direct and metal-free access toward fully substituted pyrazoles and its sulphenylation has been established through an iodine-mediated three-component [3 + 2] annulation of β-ketonitrile (or pentane-2,4-dione), arylhydrazines, and aryl sulfonyl hydrazides. The reaction allows the formation of one C–S and two C–N bonds by the multiple bond cleavage including sulfur–oxygen, sulfur–nitrogen, and carbon–oxygen bonds. The method features low-cost and readily accessible substrates, bond-forming efficiency, and broad substrate scopes as well as simple one-pot operation, which makes this strategy highly attractive.

The metal-free oxidative coupling of C2,C3-unsubstituted indoles with arylsulfonylhydrazides proceeds under mild conditions and furnishes difunctionalized indoles with good to excellent yields.

A metal-free synthesis of bifunctionalized indole derivatives was developed through a novel TBHP/TBAI-mediated oxidative coupling of C2,C3-unsubstituted indoles with arylsulfonyl hydrazide. Under the same conditions C3-methyl substituted indoles underwent a diazotization process, affording 2-sulfonyldiazenyl-1H-indoles. The former reaction simultaneously established C–S and C–N bonds through selective sulfonylation and diazotization of the indole framework, enabling a mild and practical access to polyfunctionalized indoles with good to excellent yields.

In the title compound, C12H9F3N2O2, the benzene ring is nearly perpendicular to the isoxazole ring, making a dihedral angle of 82.97 (2)°. In the crystal, molecules are linked by N—H...O hydrogen bonds into a supramolecular chain running along the c axis.

In the racemic title compound, C14H17NO6, the plane of the ester group of the methyl hexanoate side chain makes a dihedral angle of 80.0 (2)° with the benzene ring, while the nitro group is approximately coplanar with the benzene ring [dihedral angle = 10.3 (2)°]. In the crystal, molecules form weak aromatic C—H...Onitro hydrogen-bonding interactions, giving inversion dimers [graph set R22(8)].

In the crystal structure of the title compound, C6H7NO2, the molecules are are linked by intermolecular O—H...N and O—H...O hydrogen bonds; π–π stacking is observed between parallel pyridine rings of adjacent molecules [centroid-to-centroid distance = 3.7649 (12) Å].