Synthesis of Hypervalent Iodine Diazo Compounds and Their Application in Organic Synthesis.

Diazomethyl-substituted iodine(III) compounds with electron-withdrawing groups (EWG) connected to diazo methyl center were a type of donor-acceptor diazo compounds with potential reaction abilities similar to ordinary diazo compounds. Although several diazomethyl-substituted iodine(III) compounds were synthesized and used in the nucleophilic substitution reactions as early as 1994, the synthesis and application of new iodine(III) diazo compounds have only been reported to a certain extent in recent years. In the presence of rhodium catalyst, photocatalyst, or nucleophiles, diazomethyl-substituted iodine(III) compounds can be converted into rhodium-carbenes, diazomethyl radicals, ester radicals or nucleophilic intermediates, which can be used as key intermediates for the formation of chemical bonds. The aim of this review is to give an overview of diazomethyl-substituted iodine(III) compounds in organic synthesis.

Unlock the C-N Bond Amidation of Enaminones: Metal-Free Synthesis of Enamides by Water-Assisted Transamidation.

The C-N bond transamidation of primary amides with N,N-dimethyl enaminones has been efficiently realized by heating in the presence of trifluoromethanesulfonic acid (TfOH). The method enables the practical synthesis of valuable enamides without the use of any metal reagent. In addition, this transamidation protocol can also be expanded to the reactions of sulfonamides, and the late-stage functionalization on sulfonamide drugs such as Celecoxib and Valdecoxib has been verified. Moreover, the participation of water in assisting the transamidation process has been identified by the isotope labeling experiments using D2O, disclosing a new possibility in designing catalytic tactic to other transamidation reactions.

Transition-Metal-Free C-H Trifluoromethylthiolation of N,N-Disubstituted Enaminones To Access CF3S-Functionalized Enaminones and Their Application in the Synthesis of CF3S-Heteroaryls.

The α-C-H trifluoromethylthiolation of N,N-disubstituted enaminones has been achieved with simple and cheap CF3SO2Na as the CF3S source. The reactions were run at mild temperature (0 °C to rt) using POCl3 as the only reducing reagent. The work represents the first example on the synthesis of α-trifluoromethylthio enaminones via direct C-H functionalization. In addition, the resulting CF3S-functionalized enaminones have been proven as useful building blocks in the synthesis of various CF3S-functionalized heteroaromatic compounds by simple annulation reactions.

Cascade in Situ Iodination, Chromone Annulation, and Cyanation for Site-Selective Synthesis of 2-Cyanochromones.

A facile cascade reaction for the site selective synthesis of 2-cyanochromones is described. By using simple o-hydroxyphenyl enaminones and potassium ferrocyanide trihydrate (K4[Fe(CN)6]3·3H2O) as starting materials and I2/AlCl3 as promoters, the products are furnished via tandem chromone ring formation and C-H cyanation. The in situ formation of 3-iodochromone and a formal 1,2-hydrogen atom transfer (HAT) process account for the unconventional site selectivity. In addition, the synthesis of 2-cyanoquinolin-4-one has been realized by employing corresponding 2-aminophenyl enaminone as substrate.

Catalyst-Free Cascade Annulation of Enaminones and Aryl Diazonium Tetrafluoroboronates for Cinnoline Synthesis and the Anti-Inflammatory Activity Study.

A simple and concise method for the synthesis of cinnolines has been developed by the reactions of readily available enaminones and aryl diazonium tetrafluoroboronates. The reactions run efficiently to provide cinnolines with broad diversity in the substructure by heating in dimethyl sulfoxide without using any catalyst or additive. In addition, the primary investigation of the anti-inflammatory activity of these products leads to the observation of p-chlorobenzoyl (3f) and p-nitrobenzoyl (3j) cinnolines as attractive anti-inflammatory compounds in vitro.

Synergistic Visible Light and Pd-Catalyzed C-H Alkylation of 1-Naphthylamines with α-Diazoesters.

The combination of visible light irradiation and Pd-catalysis has been practically employed for the C-H alkylation reactions of naphthylamines and α-diazo esters, leading to the synthesis of α-naphthyl functionalized acetates via C-C bond construction under mild reaction conditions and under solvent-free conditions. The light irradiation has been proven to play a pivotal role in the reactions, probably by promoting the generation of active carbene species from α-diazo esters.

Rongalite as C1 Synthon in the Synthesis of Divergent Pyridines and Quinolines.

Rongalite has been used as a cheap and efficient carbon synthon for the synthesis of divergent N-heteroaromatics, including different pyridines and quinolines. The selective synthesis of different products can be achieved by employing enaminones or enaminones/anilines as reaction partners. In addition, compared with the reaction using conventional aldehyde synthons, rongalite displays an evident advantage in providing products with considerably higher product yields under milder conditions. The GC-MS analysis of the reaction process has been performed to probe the possible reaction mechanism.

Three-Component Fusion to Pyrazolo[5,1-a]isoquinolines via Rh-Catalyzed Multiple Order Transformation of Enaminones.

A facile and practical method for the synthesis of fused tricyclic pyrazolo[5,1-a]isoquinolines has been realized via the reactions of enaminones, hydrazine hydrochloride, and internal alkynes. By means of Rh catalysis, the extraordinary high-order bond functionalization, including the transformation of aryl C-H, ketone C═O, and alkenyl C-N bonds in the enaminones, marks the major feature of the cascade reactions. The results disclose the individual advantage of enaminones in the design of novel and efficient synthetic methods.

Three-Component Chemo-Selective Synthesis of N-(o-Alkenylaryl) Pyrazoles by Pyrazole Annulation and Rh-Catalyzed Chemo-Selective Aryl C-H Addition Cascade.

By using readily available enaminones, aryl hydrazine hydrochlorides, and alkynes as starting materials, the chemo-selective three-component synthesis of atropisomeric N-(o-alkenylaryl) pyrazoles has been efficiently accessed with rhodium catalysis. Unlike Satoh-Miura reaction leading to the alkyne-based C-H benzannulation by using prior prepared N-phenyl pyrazoles and alkynes as substrates, this three-component protocol displays unprecedented selectivity of C-H alkenylation by blocking the second round metal alkenylation with the key protonation step in the presence of acids.

Ultrasound-Promoted Synthesis of α-Thiocyanoketones via Enaminone C═C Bond Cleavage and Tunable One-Pot Access to 4-Aryl-2-aminothiazoles.

Ultrasound has been successfully employed to promote the thiocyanation of the C═C bond in enaminones for the synthesis of α-thiocyanoketones and 2-aminothiazoles. The reactions of enaminones with ammonium thiocyanate provide α-thiocyanoketones with ultrasound irradiation at room temperature. More interestingly, simply further heating the vessel after ultrasonic irradiation leads to the selective synthesis of 2-aminothiazoles with an unconventional 4-aryl substructure.

Photocatalytic C-H Thiocyanation of NH2-Enaminones and the Tunable Synthetic Routes to 2-Aminothiazoles and 2-Thiazolinones.

Visible light photocatalytic reactions of NH2-enaminones and ammonium thiocyanate for chemoselective α-C-H thiocyanation have been realized for the first time, providing a sustainable route for the synthesis of thiocyanated NH2-enaminones. In addition, the thiocyanated enaminone products can be flexibly transformed into 2-aminothiazoles and 2-thiazolinones via a simple operation.

Thiazole-5-carbaldehyde Synthesis by Cascade Annulation of Enaminones and KSCN with Dess-Martin Periodinane Reagent.

The Dess-Martin periodinane (DMP) reagent-mediated reactions of tertiary enaminones with potassium thiocyanate for the synthesis of thiazole-5-carbaldehydes are developed. The product formation involves cascade hydroxyl thiocyanation of the C═C double bond, intramolecular hydroamination of the C≡N bond, and thiazole annulation by condensation on the ketone carbonyl site, representing novel reaction pathways in the reactions between enaminones and thiocyanate salt. DMP plays dual roles in mediating the free radical thiocyanation and inducing the unconventional selective thiazole-5-carbaldehyde formation by masking the in situ generated formyl group during the reaction process.

Copper-Catalyzed Regiospecific Amination of Heteroarenes with Quinoneimides.

In this work, an unprecedented and widely applicable strategy for the regioselective C-3 amination of indoles and C-2 amination of heteroarenes (pyrrole and benzofuran) is presented in a simple, high-efficiency way. This protocol is also one of the few methods for the efficient construction of C-N bonds of quinoneimides by the 1,6-addition reaction.

Zinc Trifluoromethanesulfonate-Catalyzed para-Selective Amination of Free Anilines and Free Phenols with Quinoneimides.

An efficient zinc-catalyzed amination of free anilines and free phenols with quinoneimides has been disclosed, which proceeds smoothly under simple and mild conditions. The para-selective amination is accomplished on the anilines and phenols via a 1,6-addition pathway, leading to C-N bond formation. The developed protocol offers a promising approach not only for the construction of structurally diverse p-phenylenediamine compounds with excellent yields but also for the synthesis of the para-amination of free phenol derivatives with good to excellent yields. This protocol also extends the application of the quinoneimide-involved 1,6-addition reaction.

Visible-Light-Mediated Tandem Difluoromethylation/Cyclization of Alkenyl Aldehydes toward CF2H-Substituted Chroman-4-one Derivatives.

An efficient and facile visible-light-mediated tandem difluoromethylation/cyclization of alkenyl aldehydes, with easily accessible and air-stable [Ph3PCF2H]+Br- as the difluoromethylation reagent, has been established. A range of CF2H-substituted chroman-4-one skeletons and their derivatives, such as 2,3-dihydroquinolin-4(1H)-ones, chroman, 3,4-dihydronaphthalen-1(2H)-one, 2,3-dihydrobenzofuran, and 2,3-dihydro-1H-inden-1-one, are efficiently produced in moderate to good yields with excellent chemoselectivity under mild reaction conditions.

Recent advances in transition metal-free annulation toward heterocycle diversity based on the C-N bond cleavage of enaminone platform.

Enaminones and analogous stable enamines are well known as platform building blocks in organic synthesis for the construction of heterocyclic compounds, especially N-heterocycles. To date, enaminones have been successfully employed in the synthesis of various 5- or 6- membered heterocycles. Recently, synthetic protocols accomplished by diversity-oriented annulation reactions based on the C-N bond cleavage of enamines have gained notable success. In this review, the development of the transition metal-free heterocyclic product synthesis based on the annulation reactions of enaminones or analogous enamines featuring a C-N bond cleavage is reviewed.

Metal-free three-component assemblies of anilines, α-keto acids and alkyl lactates for quinoline synthesis and their anti-inflammatory activity.

A new and metal-free three-component method for the synthesis of 2,4-disubstituted quinolines via the reactions of anilines, α-keto acids and alkyl lactates is reported. The reactions proceed in the presence of p-toluene sulfonic acid (p-TSA) and tert-butyl peroxybenzoate (TBPB) to provide diverse quinoline products via the construction of new CC double, C-C single and CN double bonds without producing any organic mass-based side product. Notably, the anti-inflammatory activity of the quinolines has been investigated by measuring their ability to inhibit NO release by lipopolysaccharide (LPS) induced RAW264.7 cells, leading to the identification of 4i, 4t and 4x as potent anti-inflammatory compounds in vitro.

Visible-light-mediated tandem phosphorylation/cyclization for the synthesis of phosphorylated oxindoles.

The visible-light-mediated tandem phosphorylation/cyclization of N-arylacrylamides with H-phosphine oxides has been developed for the synthesis of phosphorylated oxindoles. This efficient and facile process was useful for the construction of a C-P bond and triggered the formation of a C-C bond with good compatibility with functional groups undermild reaction conditions.

Transition-metal-free three-component coupling approach to QUINAP derivatives.

The aluminum(III) triflate catalyzed three-component coupling reaction of alkynes, amines and phosphorylated aryl aldehydes to access phosphoryl quinoline derivatives has been developed. The reaction proceeds in a simple system without the use of transition metals, ligands or additives, thus making it attractive for the fast preparation of a variety of new potential N-P bidentate ligands.

Synthesis of 3,3-Dihalogenated 2-Aminochromanones via Tandem Dihalogenation and Cyclization of o-Hydroxyarylenaminones with NXS (X = Cl or Br).

An unprecedented method for the synthesis of dichlorinated and dibrominated 2-amino-substituted chromanones is developed by employing enaminones and NCS/NBS as starting materials under microwave irradiation. The reactions proceed quickly to deliver products without using any catalyst or additive, thus providing practical access to 3,3-dihalogenated 2-aminochromanones.