Modular Synthesis of 1,2-Benzothiazines and 1,2-Benzothiazine 1-Imines via Palladium-Catalyzed C-H/C-C Activation Reactions.

In this study, a modular approach toward cyclic sulfoximines and sulfondiimines via palladium-catalyzed intramolecular C-H/C-C activation reactions was reported. Various 1,2-benzothiazines including bicyclic, tricyclic, highly fused ones, ones of the seven-membered ring, along with 1,2-benzothiazine 1-imines were accessed in good yields. KIE experiment demonstrated that the C-H bond cleavage at the position ortho to the sulfoximine group is not the rate-determining step in the coupling reaction.

Regio- and Diastereoselective Hydrophosphination and Hydroamidation of gem-Difluorocyclopropenes.

In this study, concise, efficient, and modular hydrophosphinylation and hydroamidation of gem-difluorocyclopropenes were disclosed in a mild and transition-metal-free pattern. Through this approach, phosphorus, and nitrogen-containing gem-difluorocyclopropanes were produced in moderate to good yields with excellent regio- and diastereoselectivity. Readily available gem-difluorocyclopropenes and nucleophilic reagents, along with inexpensive inorganic bases, were employed. Multiple synthetic applications, including gram-scale and derivatization reactions and modification of bioactive molecules, were subsequently elaborated.

I2-Mediated [3 + 3] Annulation for the Construction of Indole-Pyrimidine-Pyrazole-Fused Tetracyclic Heteroarenes.

An I2-mediated annulation of 3-aminopyrazoles with indole-3-carboxaldehydes has been demonstrated for the first time. This tandem strategy allows the facile construction of indole-pyrimidine-pyrazole-fused tetracyclic heteroarenes that are otherwise inaccessible by the existing methods. These fused heterocycles exhibited enhanced antifungal activities against Valsa mali and Botryosphaeria dothidea compared with commercial Xemium fungicide.

Recent advances in palladium-catalyzed sulfonylation via SO2 insertion.

The importance of sulfonyl-group-containing compounds, such as sulfonamides, sulfones, sulfinate esters, and sulfonyl fluorides, in pharmaceuticals, bioactive molecules, and natural products cannot be overstated. The new development of palladium-catalyzed sulfonylation via SO2 insertion represents a crucial advancement in organic synthesis, enabling the direct α,α-difunctionalization of SO2 and providing efficient access to an array of structure-diverse sulfonyl-containing compounds. Although there have been numerous reviews about SO2 insertion, many of them only cover specific aspects of palladium-catalyzed reactions, leading to an oversight of some important works. Besides, these reviews often lack detailed discussions and systematic conclusion on reaction mechanisms, and fail to comprehensively summarize the significant research achievements in palladium-catalyzed reactions over the past few years. Herein, we aim to systematically consolidate the recent advances in palladium-catalyzed sulfonylation via SO2 insertion, elucidate the underlying reaction mechanism, and highlight some unsolved challenges in this segment. This review seeks to serve as a valuable resource for researchers, assisting in the continued development of palladium-catalyzed sulfonylation methodologies.

Palladium-Catalyzed Atroposelective Coupling-Cyclization of 2-Isocyanobenzamides to Construct Axially Chiral 2-Aryl- and 2,3-Diarylquinazolinones.

A palladium-catalyzed imidoylative cycloamidation of N-alkyl-2-isocyanobenzamides with 2,6-disubstituted aryl iodides, affording unprecedented axially chiral 2-arylquinazolinones, has been developed with good yields and atroposelectivities. In this coupling-cyclization process, the biaryl linkage and the heteroaromatic ring are formed sequentially in one step. When N-(2,4-dimethoxyphenyl)-2-isocyanobenzamide is applied as a substrate, 2,3-diarylquinazolinones containing two stereogenic axes are produced with moderate diastereoselectivity and good enantioselectivities.

Electrochemically promoted oxidative α-cyanation of tertiary and secondary amines using cheap AIBN.

The electrochemical α-cyanation of tertiary and secondary amines has been developed by using a cheap cyanide reagent, azobisisobutyronitrile (AIBN). The CN radical, generated through n-Bu4NBr-meidated electrochemical oxidation, participates in a novel α-cyanation reaction under exogenous oxidant-free conditions.

Photoinduced efficient synthesis of cyanoalkylsulfonylated oxindoles via sulfur dioxide insertion.

A visible-light-promoted radical cascade reaction of N-arylacrylamide and cyclobutanone oxime esters with sulfur dioxide insertion is established. Mainly through the exploration of the visible light wavelength, it is found that the light source has a certain influence on the formation of cyanoalkylsulfonylated oxindoles, furnishing a range of sulfones in good to excellent yields. This protocol presents good functional group compatibility and does not require transition metals, photosensitizers, external bases, or oxidants.

Pd-Catalyzed C(sp2)-H Imidoylative Annulation: A General Approach To Construct Dibenzoox(di)azepines.

A general method to construct the scaffolds of dibenzooxazepine and dibenzodiazepine, through Pd-catalyzed isocyanide insertion and intramolecular C(sp2)-H activation, has been developed. This is the first example of seven-membered heterocycle formation by C-H imidoylative annulation.

Enantioselective Synthesis of 2-Oxindole Spirofused Lactones and Lactams by Heck/Carbonylative Cylization Sequences: Method Development and Applications.

An efficient one-pot assembly of all-carbon spiro-oxindole compounds from non-oxindole-based materials has been developed through a palladium-catalyzed asymmetric Heck/carbonylative lactonization and lactamization sequence. Diversified spirooxindole γ-and δ-lactones/lactams were accessed in high yields with good to excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. The natural product coixspirolactam A was conveniently synthesized by applying the current methodology, and thus its absolute configuration was elucidated for the first time. Asymmetric synthesis of an effective CRTH2 receptor antagonist has also been demonstrated utilizing this method in the key step.

Copper-catalyzed N-cyanation of sulfoximines by AIBN.

The direct copper-catalyzed N-cyanation of sulfoximines was achieved by using AIBN as a safe cyanide source. It represents a simple and environmentally benign procedure for the construction of the N-CN bond. Furthermore, some sec-amines can also be tolerated well under this procedure.

Copper-catalyzed N-methylation/ethylation of sulfoximines.

A protocol for the copper-catalyzed N-methylation of sulfoximines with di-tert-butyl peroxide (DTBP) was developed. This protocol has good functional group tolerance leading to N-methylated sulfoximines in moderate to good yields. Besides, N-ethylation of sulfoximines was achieved in the presence of bis(1,1-dimethylpropyl)peroxide as the ethylating agent under a standard procedure.

Chiral phosphoric acid-catalyzed dual-ring formation for enantioselective construction of N-N axially chiral 3,3'-bisquinazolinones.

In contrast with the well-developed C-C and C-N axial chirality, research focusing on the catalytically asymmetric synthesis of N-N axially chiral compounds is still limited. As a privileged subunit of many antibiotics, the synthesis of N-N axially chiral 3,3'-bisquinazolinones has not been updated with atroposelective construction. Herein, we firstly report a chiral phosphoric acid-catalyzed dual-ring formation strategy leading to the aforementioned compounds with good chemical yields and enantioselectivities. Notably, metal-free reaction conditions are another advantage of this procedure.

Visible-Light Photosynthesis of CHF2 /CClF2 /CBrF2 -Substituted Ring-fused Quinazolinones in Dimethyl Carbonate.

With eco-friendly and sustainable CO2 -derived dimethyl carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2 /CClF2 /CBrF2 -substituted ring-fused quinazolinones.

Ultrasound-Assisted Iodination of Imidazo[1,2-α]pyridines Via C-H Functionalization Mediated by tert-Butyl Hydroperoxide.

A novel metal catalyst-free and environmentally friendly method for the regioselective iodination of imidazo[1,2-α]pyridines at their C3 position is disclosed, which has a wide substrate scope and could be sustainable. This reaction proceeds through ultrasound acceleration in the presence of a green alcohol solvent. Compared with a conventional heating system, the reaction efficiency and the rate are significantly improved and the iodine atom economy is maximized using ultrasound techniques.

[2 + 2 + 1] Heteroannulation of Alkenes with Enynyl Benziodoxolones and Silver Nitrite Involving C≡C bond Oxidative Cleavage: Entry to 3-Aryl-Δ2-isoxazolines.

A copper-catalyzed [2 + 2 + 1] heteroannulation of alkenes with enynyl benziodoxolones and AgNO2 involving oxidative cleavage of the C≡C bond promoted by cooperative Zn(OTf)2, KOAc, and 4 Å MS for producing 3-aryl Δ2-isoxazolines is reported. Mechanistic studies indicate that AgNO2 serves as the N/O two-atom unit source, enabling the formation of three bonds through NO2 addition across the C≡C bond, NO-transfer, C≡C bond cleavage, and annulation cascades.

Relay Palladium/Copper Catalysis Enabled Silylative [5 + 1] Benzannulation Using Terminal Alkynes as One-Carbon Units.

Using terminal alkyne as a nontraditional one-carbon (C1) unit and silylborane as an external silicon pronucleophile, a relay palladium/copper-catalyzed silylative [5 + 1] benzannulation of 3-acetoxy-1,4-enynes for producing polysubstituted arylsilanes, especially including bioactive motif-based analogues, in a single reaction step through benzene ring skeleton assembly and silyl intermolecular incorporation cascades is developed. Mechanistic studies show that this reaction allows the terminal sp-hybridized carbon atom in terminal alkynes as a C1 unit via cleavage of two π-bonds and one C(sp)-H bond.

Pd-Catalyzed Domino Imidoylation/Heck/C(sp2)-H Cyclization: Isocyanide Relay Strategy toward Tricyclic-Fused Heterocycles Containing an All-Carbon Quaternary Center.

A palladium-catalyzed domino process for the quick assembly of tricyclic-fused heterocycles starting from aryl iodides and functionalized isocyanides containing a disubstituted terminal alkene has been developed. The process is triggered by intermolecular isocyanide insertion, followed by Heck-type carbopalladation of the intramolecular alkene moiety and subsequent C(sp2)-H activation. Moreover, an asymmetric version of this reaction could also be realized in good yield with moderate enantioselectivity after preliminary exploration of chiral ligands.

Oxidative [4+2] Cycloaddition of α-(N-Arylamino) Carbonyls with Aryl Alkenes by Multiple C-H Functionalizations and [1,2]-Aryl Shifts.

A new, general copper-catalyzed oxidative tandem [4+2] cycloaddition of α-(N-arylamino) carbonyl compounds with aryl alkenes to produce highly substituted quinolines has been developed, which allows the formation of three new C-C bonds through a sequence of multiple C-H functionalizations, annulation, and [1,2]-aryl shifts.

One-Carbon Incorporation Using Cyclobutanone Oxime Ester Enabled [2 + 2 + 1] Carboannulation of 1,7-Enynes by C-C/N-O Bond Cleavage and C-H Functionalization.

A NiCl2-promoted [2 + 2 + 1] carboannulation of 1,7-enynes with internally oxidative cyclobutanone oximes to produce canyo-functionalized 4H-cyclopenta[c]quinolin-4-ones is disclosed. Through C-C/N-O bond cleavage and C-H functionalization, the process enables one-carbon incorporation using cyclobutanone oximes to achieve [2 + 2 + 1] carboannulation of 1,7-enynes, which is highlighted by allowing the formation of four new bonds with high selectivity and broad substrate scope.

Silver-catalyzed oxidative 1,2-alkyletherification of unactivated alkenes with α-bromoalkyl carbonyls: facile access to highly substituted 2,3-dihydrofurans.

A new, general silver-catalyzed oxidative 1,2-alkyletherification of unactivated olefinic ketones with primary, secondary and tertiary α-bromoalkyl carbonyls promoted by tert-butyl hydroperoxide (TBHP) and Et3N has been developed. Through the cooperative action of Ag2O, TBHP and Et3N, the reaction enables the construction of highly valuable quaternary-carbon-possessing 2,3-dihydrofuran frameworks using a concomitant intramolecular annulation strategy.