Nitrogen-Nitrogen Radical Coupling-Enabled Precise Difunctionalization of Carbon-Nitrogen Double Bonds.

In this study, we have developed a metal-free, photoinduced energy transfer strategy for the efficient difunctionalization of carbon-nitrogen double bonds (C═N). Utilizing oxime ester-based bifunctional reagents, we have achieved direct radical difunctionalization of C═N bonds through nitrogen-nitrogen radical coupling, with over 35 examples and yields up to 96%. This method exhibits broad substrate scope, being compatible with a variety of carboxylic acids and biologically active molecules, thus offering a novel approach for the difunctionalization of heteroatom-containing unsaturated bonds in synthetic chemistry.

Photocatalytic Unsymmetrical Diamination of Styrenes, Indoles, and Benzofurans Facilitated by Benzotriazolyl and Iminyl Radicals.

Utilizing energy transfer catalysis, this research employed the bifunctional reagents benzotriazole carboxylic acid oxime esters to simultaneously generate benzotriazole and imine radicals. The synthesis of two distinct C-N bonds in a single conversion is showcased through radical addition and radical-radical cross-coupling processes between benzotriazole carboxylic acid oxime ester and olefins. This process facilitates the intermolecular two-component unsymmetrical diamination reaction of olefins.

The Merger of Halogen Atom Transfer (XAT) and Energy Transfer Catalysis (EnT) for the Modular 1,2-Iminylalkylation of Diazenes.

The 1,2-iminylalkylation of diazenes using alkyl iodides in combination with an -benzoyl oxime is reported. In this transformation, -benzoyl oxime acted as a radical precursor and XAT mediator. In addition to common alkyl iodides, other alkyl iodides such as iodomethane, iodomethane-, trifluoroiodomethane, ethyl difluoroiodoacetate, and iodoalkanes containing unprotected hydroxyl and amide groups can also serve as C-radical precursors in the 1,2-iminylalkylation with electrophilic diazenes as radical acceptors.

Photoinduced Difunctionalization of Diazenes Enabled by N-N Radical Coupling.

In this study, a metal-free difunctionalization strategy for diazenes was developed using a range of bifunctionalization reagents. This strategy involves a unique N(sp)-N(sp) radical coupling between the hydrazine radical and the imine radical. More than 30 triazane core motifs were constructed by installing imines and various functional groups, including alkyl, phenyl, cyanoalkyl, and sulfonyl groups, on both ends of the nitrogen-nitrogen bond of diazenes in an efficient manner.

Photocatalytic Multicomponent 1,-Carboimination with Alkyl Iodides and -Benzoyl Oxime through EnT and XAT Processes.

In this study, we developed a strategy using commercially available alkyl iodides and -benzoyl oxime to efficiently introduce alkyl and iminyl groups via energy transfer and halogen-atom transfer processes. We performed three-component 1,2-carboimination of olefins and four-component 1,4-carboimination across olefins and alkynes, resulting in the synthesis of over 60 nitrogen-containing molecules. Moreover, this transformation enables the synthesis of molecules with sensitive groups that were previously difficult to achieve.

Diastereoselective Access to Seven-Membered Benzosultams via Palladium-Catalyzed Ring-Opening [3 + 2]-Annulation.

A palladium-catalyzed ring-opening [3 + 2]-annulation of spirovinylcyclopropanyl oxindoles with seven-membered cyclic -sulfonylimines has been developed. A wide range of seven-membered benzosultams featuring both a quaternary center and axially chiral biaryl scaffolds have been afforded in an average yield of 87% with moderate to excellent diastereoselectivities. The enantioenriched benzosultams were also accessed successfully in good yields with excellent atropoenantioselectivities enabled by the Pd(dba)/(,,)-SKP ligand.

Visible-light-driven oxidation of organosilanes by a charge-transfer complex.

Direct oxidation of organosilanes is one of the most straightforward ways to access silanols. Herein, we describe a novel photo-induced strategy for oxidation of organosilanes to access silanols, promoted by a photoactive charge-transfer complex (CTC) between sodium benzenesulfinate and molecular O. A streamlined sequence transformation of organosilanes to silyl ethers was also readily achieved.

Photocatalytic 1,2-Iminosulfonylation and Remote 1,6-Iminosulfonylation of Olefins.

A new class of iminosulfonylation reagents were developed and extensively used in the 1,2-iminosulfonylation of various olefins. Olefins containing bioactive molecules, such as indomethacin, gemfibrozil, clofibrate, and fenbufen, afforded the desired iminosulfonylation products in synthetically useful yields. Furthermore, the first remote 1,6-iminosulfonylation of alkenes was realized by using oxime ester bifunctionalization reagents.

Photoinduced Remote C(sp)-H Imination Enabled by Vinyl Radical-Mediated 1,5-Hydrogen Atom Transfer.

A vinyl radical-mediated 1,5-hydrogen atom transfer strategy for remote C(sp)-H imination under visible-light-induced photochemical metal-free conditions afforded diverse γ-imino alkenes with excellent stereoselectivity. Oxime ester-based bifunctional reagents provided not only nucleophilic alkyl radicals for radical addition reactions with electron-deficient alkynes but also long-lived steady-state imine radicals for trapping alkyl radicals following the intramolecular 1,5-hydrogen migration of unstable olefin radicals.

Photocatalytic Modular Cyanoalkylamination of Alkenes Involving Two Different Iminyl Radicals.

The modular cyanoalkylamination of alkenes using bench-stable and easy-to-handle α-imino-oxy acid oxime esters as difunctional reagents creates new synthetic avenues. A metal-free photosensitization protocol for the installation of both amino and cyanoalkyl functionalities onto alkene feedstocks in a single step via two differently reactive nitrogen-centered radicals was developed via energy-transfer catalysis. Excellent functional group tolerance and mild reaction conditions also render this protocol suitable for the cyanoalkylamination of pharmaceutically relevant molecule-derived alkenes.

Photochemical Organocatalytic Aerobic Cleavage of C═C Bonds Enabled by Charge-Transfer Complex Formation.

A novel visible-light-driven organocatalytic protocol to access aerobic oxidative cleavage of olefins, promoted by sodium benzene sulfinate, is described herein. An array of alkenes smoothly delivered the corresponding aldehydes and ketones under transition-metal-free conditions. Notably, α-halo-substituted styrenes proceeded with photoinduced oxidation to finally afford α-halo-acetophenones with halogen migration.

Visible-Light-Driven, Photocatalyst-Free Cascade to Access 3-Cyanoalkyl Coumarins from -Hydroxycinnamic Esters.

A visible-light-driven, photocatalyst-free route starting from easily accessed -hydroxycinnamic esters and -perfluoropyridin-4-yl oximes has been successfully developed to rapidly assemble a wide range of 3-cyanoalkyl coumarins. This process does not require addition of external photocatalysts, exhibiting beneficial features including mild reaction conditions, synthetic simplicity, and excellent substrate compatibility. Extensive mechanistic investigations revealed that the in situ generated phenolate anions served as photosensitizers to drive this photoinduced transformation.

Photocatalytic Hydroacylation of Alkenes by Directly Using Acyl Oximes.

Acyl oximes are directly used as the acyl radical precursors in the hydroacylation reactions for the first time. In this work, acyl radicals can be effectively generated -scission of a phosphoranyl radical under photocatalytic conditions. As a result, the hydroacylation of alkenes triggered by the resulting acyl radicals leads to facile syntheses of a range of valuable ketones.

Visible-Light-Induced, Catalyst-Free Radical Cross-Coupling Cyclization of -Allylbromodifluoroacetamides with Disulfides or Diselenides.

A visible-light-induced, catalyst-free radical cross-coupling cyclization of diselenides or disulfides with -allylbromodifluoroacetamide has been developed. This developed protocol exhibits good functional group tolerance and affords a variety of 4-thio- and 4-seleno-substituted 3,3-difluoro-γ-lactams in moderate to good yields. Based on control experiments, a plausible radical-radical cross-coupling pathway is proposed.

Photocatalytic C-F Bond Borylation of Polyfluoroarenes with NHC-boranes.

The first photoredox-catalyzed defluoroborylation of polyfluoroarenes with NHC-BH has been facilely achieved at room temperature via a single-electron-transfer (SET)/radical addition pathway. This new strategy makes full use of the advantage of photoredox catalysis to generate the key boryl radical via direct activation of a B-H bond. Good functional group tolerance and high regioselectivity offer this protocol incomparable advantages in preparing a wide array of valuable polyfluoroarylboron compounds.

-Perfluoropyridin-4-yl Oximes: Iminyl Radical Precursors for Photo- or Thermal-Induced N-O Cleavage in C(sp)-C(sp) Bond Formation.

-Perfluoropyridin-4-yl group was first installed onto cycloketone oximes as a new electrophore, which was proven to be efficient iminyl radical precursors under photocatalytic and thermal conditions. A range of -perfluoropyridin-4-yl oximes were successfully utilized in C(sp)-C(sp) bond formations of quinoxalin-2(1)-ones and alkenes, providing facile accesses to a range of functionalized alkylnitriles.

Photoinduced Single-Electron Transfer as an Enabling Principle in the Radical Borylation of Alkenes with NHC-Borane.

A photoinduced SET process enables the direct B-H bond activation of NHC-boranes. In contrast to common hydrogen atom transfer (HAT) strategies, this photoinduced reaction simply takes advantage of the beneficial redox potentials of NHC-boranes, thus obviating the need for extra radical initiators. The resulting NHC-boryl radical was used for the borylation of a wide range of α-trifluoromethylalkenes and alkenes with diverse electronic and structural features, providing facile access to highly functionalized borylated molecules.

Visible-Light-Driven, Photoredox-Catalyzed Cascade of ortho-Hydroxycinnamic Esters To Access 3-Fluoroalkylated Coumarins.

A general and straightforward protocol for di-/perfluoroalkylation of ortho-hydroxycinnamic esters via a photoredox-catalyzed cascade was developed to access a variety of 3-fluoroalkylated coumarins. This method was characterized by all-in-one synthetic design, simplified operation, mild reaction conditions, and broad substrate scope. Moreover, a sequential one-pot procedure starting from commercially available salicylaldehyde was also successfully realized to synthesize 3-fluoroalkylated coumarins.

Photocatalytic, Phosphoranyl Radical-Mediated N-O Cleavage of Strained Cycloketone Oximes.

A photoinduced, phosphoranyl radical-mediated protocol for the direct N-O cleavage of strained cycloketone oximes via a polar/SET crossover process was developed for the first time. This visible-light-driven direct N-O activation mode for oxime offers beneficial features such as streamlined synthetic process and versatile photochemical reactivities. Consequently, the alkenes and α-trifluoromethyl alkenes with varied electronic and structural features acted as competent radical receptors in this protocol, enabling facile accesses to a range of elongated cyano and/or gem-difluoroalkene-bearing compounds.

A One-Pot Ring-Opening/Ring-Closure Sequence for the Synthesis of Polycyclic Spirooxindoles.

One-pot ring-opening/ring-closure process of combining methyleneindolinone with 3-aminooxindole has been developed in this work. Novel polycyclic spirooxindoles were efficiently assembled under mild conditions in high yields (up to 95 %) with moderate to good diastereoselectivities (up to >95:5 d.r.

Photocatalytic reductive radical-radical coupling of N,N'-cyclicazomethine imines with difluorobromo derivatives.

A visible-light-induced difluoroalkylation of N,N'-cyclicazomethine imine was successfully realized through a novel photoredox radical-radical cross-coupling reaction. This developed protocol exhibits high functional group tolerance and affords a variety of difluorinated 3-pyrazolidinone scaffolds. Extensive mechanistic investigations have been undertaken, well revealing the involvement of a reductive radical-radical coupling pathway.

Palladium-catalysed ring-opening [3 + 2]-annulation of spirovinylcyclopropyl oxindole to diastereoselectively access spirooxindoles.

A novel palladium-catalysed ring-opening [3 + 2]-annulation of spirovinylcyclopropyl oxindole with α,β-unsaturated nitroalkenes is reported. A series of spirooxindole derivatives were synthesized in high yields and good to excellent diastereoselectivities. This developed protocol offers a new and efficient pathway for the assembly of spirooxindoles.

Unraveling and Manipulating the Stereospecific Retro-Aldol Reaction in the Organocatalytic Asymmetric Aldol Reaction of Isatin and Cyclohexanone.

An l-pyroglutamic acid-derived bifunctional organocatalyst was designed and applied in an organocatalytic asymmetric direct aldol reaction between isatins and cyclohexanone, in which an erosion of enantiomeric excess of aldol adduct was unexpectedly observed. Through closely monitoring the reaction and performing extensive control experiments, it was determined that the erosion of ee was attributed to a rare stereospecific retro-aldol process. Moreover, effective manipulation of the retro-aldol process by tuning the use of starting materials was ultimately accomplished, leading to evidently upgraded enantioselectivity and functional group tolerance.

Organocatalytic Domino Entry to an Octahydroacridine Scaffold Bearing Three Contiguous Stereocenters.

A facile and enantioselective access to a functionalized octahydroacridine scaffold was developed via an organocatalytic domino sequence between cyclohexenone and 2- N-substituted benzaldehyde. High levels of yields (up to 99%) and enantioselectivities (up to 99:1 er) were readily achieved in this developed organocatalytic transformation, which holds promising applications in the construction of complex multicyclic systems for further pharmacological studies.

Visible-Light-Induced External Radical-Triggered Annulation To Access CF-Containing Benzoxepine Derivatives.

A facile and diversified synthesis of functionalized CF-containing benzoxepine derivatives via photoredox catalysis was achieved in this work. This novel protocol features broad substrate scope, mild reaction conditions, operational simplicity, easy scale-up, and versatile derivatization, which would facilitate its practical and broad applications in the construction of valuable and synthetically challenging heterocycles.