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

A visible-light-driven, photocatalyst-free route starting from easily accessed ortho-hydroxycinnamic esters and O-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.

O-Perfluoropyridin-4-yl Oximes: Iminyl Radical Precursors for Photo- or Thermal-Induced N-O Cleavage in C(sp2)-C(sp3) Bond Formation.

O-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 O-perfluoropyridin-4-yl oximes were successfully utilized in C(sp2)-C(sp3) bond formations of quinoxalin-2(1H)-ones and alkenes, providing facile accesses to a range of functionalized alkylnitriles.

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 via ß-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 N-Allylbromodifluoroacetamides with Disulfides or Diselenides.

A visible-light-induced, catalyst-free radical cross-coupling cyclization of diselenides or disulfides with N-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.

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. Labeling and photoquenching experiments provide insight into the mechanism of this photoinduced SET pathway.

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.) through simple filtration.

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.

Solvent-Minimized, Chromatography-Free, Diastereoselective Synthesis of Oxazolidine-Dispirooxindoles via oxa-1,3-Dipolar Cycloaddition of 3-Oxindole.

An efficient and diastereoselective decarboxylative oxa-1,3-dipolar cycloaddition between 3-oxindoles and diverse amino acids is developed to access novel oxazolidine-dispirooxindole skeletons bearing vicinal quaternary carbon centers. This protocol features operational simplicity, a broad substrate scope, and good to excellent chemical yields and diastereoselectivities. In particular, minimal solvent (1 mL/10 mmol) and chromatography-free purification render this synthetic process more efficient and environmentally benign in the context of green chemistry.

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.

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,ß-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.

Photoredox-Catalyzed Reductive Dimerization of Isatins and Isatin-Derived Ketimines: Diastereoselective Construction of 3,3'-Disubstituted Bisoxindoles.

Reductive dimerization of isatin and its derivatives can be regarded as a step-economical pathway to construct 3,3'-disubstituted bisoxindoles, which was unfortunately accompanied by severe direct reduction as well as low efficiency. A visible-light driven, photoredox-catalytic protocol was developed to readily furnish 3,3'-dihydroxy- (dl-, > 20:1 dr) and 3,3'-diamino-bisoxindoles (meso-, 3.5:1 to 5:1 dr) in moderate to good yields, successfully circumventing the common problem. Two vicinal quaternary carbon centers were effectively assembled under the irradiation of visible light.

Selectfluor-Triggered Tandem Cyclization of o-Hydroxyarylenaminones To Access Difluorinated 2-Amino-Substituted Chromanones.

A practical and straightforward synthetic route through a Selectfluor-triggered tandem cyclization of o-hydroxyarylenaminone was developed to construct a variety of difluorinated 2-amino-substituted chromanones. This novel protocol features mild reaction conditions, operational simplicity, and broad substrate scope. The enamine moiety in o-hydroxyarylenaminone played dual roles to enable high efficiency in the difluorination and intramolecular cyclization, leading to the accomplishment of a new class of difluorinated 2-amino-substituted chromanones for pharmaceutical studies.

Organocatalytic Asymmetric Allylic Alkylation of Morita-Baylis-Hillman Carbonates with Diethyl 2-Aminomalonate Assisted by In Situ Protection.

With the aid of in situ protection by N-(2-formylphenyl)-4-methyl-benzenesulfonamide, enantioselective allylic alkylation of Morita-Baylis-Hillman carbonates with diethyl 2-aminomalonate was successfully realized. The corresponding adducts can be obtained in up to 99% yield with up to 98% ee as well as excellent regioselectivity. Besides, the adducts with opposite configurations were readily prepared by utilizing easily available and inexpensive quinine or quinidine as organocatalyst. Facile deprotection of the resulting adduct provides straightforward access to enantiopure α-methylene-γ-lactam.

Diversity-driven and facile 1,3-dipolar cycloaddition to access dispirooxindole-imidazolidine scaffolds.

A diversity-driven three-component 1,3-dipolar cycloaddition of isatins, amino acids and isatin-derived ketimines was developed to facilely assemble dispirooxindole-imidazolidine skeletons bearing vicinal quaternary carbon centers. This protocol features additive-free, minimal solvent usage (0.1 mL DMSO/0.2 mmol scale), wide substrate scope (34 examples), mild reaction conditions (room temperature) and high chemical yield (up to 99%).

Diastereoselective Intramolecular [3 + 2]-Annulation of Donor-Acceptor Cyclopropane with Imine-Assembling Hexahydropyrrolo[3,2-c]quinolinone Scaffolds.

An intramolecular [3 + 2]-annulation of amide-linked donor-acceptor cyclopropane with in situ-generated imine is described. As a result, diverse hexahydropyrrolo[3,2-c]quinolinones, as the tricyclic core of martinellines, were efficiently assembled in good to excellent yield (up to 93%) with a good diastereomeric ratio (up to 98:2).

Regioselectivity-Tunable Self-1,3-Dipolar [3+3] Cyclizations of Azomethine Ylides To Assemble Dispirooxindole-piperazines.

A series of novel 2,3- or 2,5-dispirooxindole-piperazine ring systems were efficiently constructed through the acid-promoted self-1,3-dipolar [3+3] cyclizations of azomethine ylides derived from isatin with various primary or cyclic secondary amines. Interestingly, the regioselectivity of this self-[3+3] cyclization could be effectively tuned by varying the structural features of substrates. The unprecedented 2,5-dispirooxindole-piperazine skeleton was achieved in good diastereoselectivity by employing 1,2,3,4-tetrahydroisoquinoline, while using pyrrolidine or glycine methyl ester furnished the 2,3-dispirooxindole-piperazine scaffold in excellent diastereoselectivity (only a single isomer formed).

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. Using this approach, more than 40 benzotriazole-containing molecules were successfully synthesized using styrene, indole, and benzofuran as acceptors, with yields ranging from moderate to excellent.

Photoinduced Remote C(sp3)-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(sp3)-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.

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(sp3)-N(sp2) 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,n-Carboimination with Alkyl Iodides and O-Benzoyl Oxime through EnT and XAT Processes.

In this study, we developed a strategy using commercially available alkyl iodides and O-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.