Bioinspired Synthesis of Phelligridin Analogues via Ru-Catalyzed C-H Activation/[4 + 2] Annulation of Aryl Imidates with Heteroaromatic Iodonium Ylides.

The first Ru(II)-catalyzed C-H activation/[4 + 2] annulation of aryl imidates with heteroaromatic iodonium ylides is reported. Our approach features the utilization of a commercially available ruthenium catalyst, providing a one-step construction of phelligridin analogues from easily available and nonpreactivated starting materials. The developed methodology is successfully employed for the total synthesis of phelligridin A, significantly streamlining previous multistep synthesis.

Cyclic Iodonium Ylide Unlocked Pd-Catalyzed α-Acyloxylation of Cyclic 1,3-Dicarbonyls with Carboxylic Acids.

To date, a general approach for the direct α-acyloxylation of cyclic 1,3-dicarbonyls remains challenging. Herein, we report a Pd-catalyzed α-acyloxylation of cyclic 1,3-dicarbonyl-derived hypervalent iodine compounds with highly abundant carboxylic acids. Our approach utilizes a commercially available Pd(OAc) catalyst, which exhibits mild reaction conditions, scalability, operational simplicity, and robustness against moisture and air.

Rh-Catalyzed α-Arylation of Cyclic 1,3-Dicarbonyls with Benzocyclobutenols Enabled by a Cyclic Iodonium Ylide Strategy.

To date, the general and catalytic α-arylation of cyclic 1,3-dicarbonyls remains elusive. We now report the first Rh-catalyzed α-arylation of cyclic 1,3-dicarbonyls with benzocyclobutenols through a cyclic iodonium ylide strategy. Our strategy represents a good solution for the previously challenging α-arylation of cyclic 1,3-dicarbonyls with sterically demanding aryl partners, which is especially appropriate for structurally unique heteroaromatic 1,3-dicarbonyls.

Ru(II)-Catalyzed Carboamination of Olefins with α-Carbonyl Sulfoxonium Ylides.

The first ruthenium-catalyzed carboamination of olefins with α-carbonyl sulfoxonium ylides is reported. The utilization of an inexpensive ruthenium catalyst enables the concise synthesis of pharmaceutically important isoindolin-1-ones, which possess both a stereogenic center and β-carbonyl side chain. This method is mild, efficient, and scalable and allows for the coupling of a wide range of aryl-, heteroaryl-, alkenyl-, and alkyl-substituted sulfoxonium ylides.

Rhodium-Catalyzed Difunctionalization of Alkenes Using Cyclic 1,3-Dicarbonyl-Derived Iodonium Ylides.

Herein, we introduce an iodonium ylide strategy to achieve novel α-alkylation of cyclic 1,3-dicarbonyls through harnessing C(sp)-Rh species generated from 5-- cyclization to provide rapid access to molecular hybridization of medically important isoindolin-1-ones and cyclic 1,3-dicarbonyls from readily available substrates. This approach features mild conditions, good yield, excellent functional group tolerance, and the simultaneous formation of two new chemical bonds and one stereogenic center. Moreover, the hydroxyl group of resulting product provides a good handle for downstream transformations.

Catalytic and Base-free Suzuki-type α-Arylation of Cyclic 1,3-Dicarbonyls via a Cyclic Iodonium Ylide Strategy.

To date, it remains challenging to achieve a general and catalytic α-arylation of cyclic 1,3-dicarbonyls, particularly ubiquitous heteroaromatic ones. In most cases, the preparation of their medically significant arylated derivatives requires multistep synthetic sequences. Herein, we introduce a new, convenient strategy involving the conversion of cyclic 1,3-dicarbonyls to cyclic iodonium ylides (CIYs), followed by rhodium-catalyzed α-arylation with arylboronic reagents via carbene coupling.

Rh(III)-Catalyzed C-H Annulation of Alkenyl- or Arylimidazoles and (Hetero)cyclic 1,3-Dicarbonyl Compounds: A Rapid Access to Imidazo-Fused Polycyclic Compounds.

A novel strategy for the synthesis of imidazo-fused polycyclic compounds under mild, base-free, and silver-free conditions by a rhodium(III)-catalyzed C-H annulation of alkenyl or arylimidazoles and (hetero)cyclic 1,3-dicarbonyl compounds is reported here. Such a step-economic protocol features the selective cleavage of two different C-H bonds in one step, featuring easy operation, readily available starting materials, gram-scale synthesis, broad functional group tolerance, and no requirement to presynthesize carbene precursors. Notably, the synthetic potential is showcased by the structural modification of drug and the highly step-economic synthesis of Janus kinase inhibitor in only three steps with a satisfactory 26% total yield (previous method: in nine steps with 0.

Aromatic Acids and Leucine Derivatives Produced from the Deep-Sea Actinomycetes SCSIO15079 with Antihyperlipidemic Activities.

Six new aromatic acids (-) and three new leucine derivatives containing an unusual oxime moiety (-) were isolated and identified from the deep-sea-derived actinomycetes strain SCSIO15079, together with two known compounds (-). The structures of - including absolute configurations were determined by detailed NMR, MS, and experimental and calculated electronic circular dichroism spectroscopic analyses. Compounds - were evaluated for their antimicrobial and cytotoxicity activities, as well as their effects on intracellular lipid accumulation in HepG2 cells.

Synthesis and antitumor activity of new tetrahydrocurcumin derivatives click reaction.

Three new derivatives of tetrahydrocurcumin , and have been prepared as potent antitumor agents using copper(II)-catalyzed 'click chemistry'. Their structures were identified using H-NMR, C-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116).

Biomimetic Carbene Cascades Enabled Imine Derivative Migration from CarbeneBearing Thiocarbamates.

Inspired by the body circulation of Omeprazole (irreversible proton pump inhibitor), we disclose the carbene-triggered cascades for the synthesis of 2-aminobenzofuran derivatives from -sulfonyl-1,2,3-triazoles or benzothioazole-bearing thiocarbamates, which represents an unprecedented imine derivative migration process. Furthermore, the desulfurizing reagent-free Barton-Kellogg-type reactions starting from -sulfonyl-1,2,3-triazoles have also been achieved for the first time, and elemental sulfur is confirmed as a byproduct during this transformation. Both experimental data and DFT calculations further thoroughly explained the unique reactivity.

Cu-Catalyzed -Amino Benzofuranthioether Formation from -Tosylhydrazone-Bearing Thiocarbamates and Arylative Electrophiles.

An important framework of -amino benzofuranthioethers was constructed by Cu-catalyzed arylative cyclization of -tosylhydrazone-bearing thiocarbamates with silylaryl triflates or ArI. This transformation provides a novel strategy for the synthesis of valuable arylative -amino benzofuranthioethers in moderate yields which could not be obtained from known methods. The reaction features smart design, efficient construction, and mild reaction conditions.

Palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides.

Cross-coupling reactions involving metal carbene intermediates play an increasingly important role in C-C bond formation. Expanding the carbene precursors to a broader range of starting materials and more diverse products is an ongoing challenge in synthetic organic chemistry. Herein, we report a Suzuki-Miyaura coupling reaction of in situ-generated Pd-carbene complexes via desulfurization of thioureas or thioamides.

Synthesis of anti-vicinal diboronates from diarylethynes and Bpin.

Anti-vicinal diboronates were fabricated from easily available diarylethynes and Bpin via a base-catalyzed domino-borylation-protodeboronation (DBP) strategy under transition-metal-free conditions. Under the standard conditions, reactants with a range of different classes of functional groups on the rings, such as MeO, MeS, CFO, MeN, TMS, I, Br, Cl, F, and the thiophene ring, were tolerated. Downstream transformation of the vicinal diboronates provided a facile pathway for obtaining vicinal diols by mild oxidation with NaBO, and a new deuteriation technique was developed in order to acquire 1,2-diarylethanes-1,2-d and 1,2-diarylethanes-1,1,2,2-d.

Cu-Catalyzed Denitrogenative Ring-Opening of 3-Aminoindazoles for the Synthesis of Aromatic Nitrile-Containing (Hetero)Arenes.

An unprecedented Cu-catalyzed oxidative cleavage of two C-N bonds of 3-aminoindazoles is reported herein, which represents the first example for denitrogenative ring-opening of 3-aminoindazoles. This novel reactivity of 3-aminoindazoles enables the production of diverse aromatic nitrile-containing (hetero)arenes via C-H arylation of (hetero)arenes with wide subsrate scope under mild conditions.

Diversity-oriented synthesis of imidazo[2,1-a]isoquinolines.

Herein, we report an efficient and practical strategy for the synthesis of five types of imidazo[2,1-a]isoquinolines via Cp*RhIII-catalyzed [4+2] annulation of 2-arylimidazoles and α-diazoketoesters, whose structural and substituted diversity at 5- or 6-position can be precisely controlled by the α-diazoketoester coupling partners. Compared with previous reports, in this study, we merged two attractive C-C cleavage strategies (retro-Claisen and decarboxylation) into the classical C-H functionalization/condensation process by choosing appropriate ester groups (-COOEt, -COOtBu or -COOiPr) or inexpensive additives (HOAc or KOAc). Moreover, the synthetic efficacies of these methods were demonstrated by the concise synthesis of several bioactive compounds and the late-stage modification of representative drugs.

Dual role of ethyl bromodifluoroacetate in the formation of fluorine-containing heteroaromatic compounds.

An efficient one-pot cascade process via unprecedented quadruple cleavage of BrCFCOOEt with primary amines to afford valuable fluorine-containing heterocycles is described, in which BrCFCOOEt plays a dual role as a C1 synthon and a difluoroalkylating reagent for the first time. Mechanistic studies supported by DFT calculations suggest that a base plays an active role in the formation of the key intermediate isocyanides generated in situ from primary amines and difluorocarbene.

Rh(ii)/phosphine-cocatalyzed synthesis of dithioketal derivatives from diazo compounds through simultaneous construction of two different C-S bonds.

Rhodium(ii)/phosphine-cocatalyzed bis-sulfuration of α-diazocarbonyl compounds using thiosulfonates as the sulfenylating agent, which provided two sulfur-containing moieties, was developed via simultaneous inter- and intra-molecular C-S bond formation. This novel protocol provides a rapid synthetic route to dithioketal derivatives in moderate to good yields in an atom-economic process. The transformation is proposed to proceed through phosphine ylide formation followed by S(O2)-S bond cleavage and rearrangement.

Thiocarbamate-Directed Tandem Olefination-Intramolecular Sulfuration of Two Ortho C-H Bonds: Application to Synthesis of a COX-2 Inhibitor.

A palladium-catalyzed dual ortho C-H bond activation of aryl thiocarbamates is developed. This tandem reaction initiates by thiocarbamate-directed ortho C-H palladation, which leads to favorable olefin insertion rather than reductive elimination. The oxidative Heck reaction followed by another C-H activation and sulfuration affords the dual-functionalized products.

Cu-Catalyzed Synthesis of 3-Formyl Imidazo[1,2-a]pyridines and Imidazo[1,2-a]pyrimidines by Employing Ethyl Tertiary Amines as Carbon Sources.

A highly efficient synthesis of 3-formyl imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine, under Cu-catalyzed aerobic oxidative conditions and by utilizing ethyl tertiary amines as carbon sources, is disclosed. A novel activation mode of ethyl tertiary amines in which simultaneous selective cleavage of C-C bond and C-N bond of ethyl group with molecular oxygen as terminal oxidant in this one-pot protocol is reported for the first time. This reaction features broad substrate scope, good functional group tolerance, as well as diversified and valuable products.

Merging gold catalysis, organocatalytic oxidation, and Lewis acid catalysis for chemodivergent synthesis of functionalized oxazoles from N-propargylamides.

Novel catalytic systems consisting of cationic gold complexes, N-hydroxyphthalimide (NHPI), and transition-metal-based Lewis acids have been developed for the one-pot synthesis of functionalized oxazoles from N-propargylamides with excellent functional group tolerance. These transformations demonstrated the excellent compatibility of homogeneous gold catalysis with organocatalytic oxidative carbon-nitrogen bond formations using tert-butyl nitrite as the terminal oxidant. Moreover, oxazolecarbonitriles or carboxamides can be easily synthesized in a one-pot protocol according to the different synthetic requirements.

Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2-Aminofurans From N-Tosylhydrazone-Bearing Thiocarbamates.

An efficient and convenient synthesis of valuable disulfanes and benzenesulfonothioates, having a 2-aminofuran framework, has been developed by employing a copper-catalyzed transformation of readily available N-tosylhydrazone-bearing thiocarbamates. This method features an inexpensive metal catalyst, mild reaction conditions, good functional-group tolerance, short reaction times, and delivers valuable and complex products. A copper carbene generated from an N-tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the transformation and it triggers the subsequent cascade.

Chemoselective acylation of benzimidazoles with phenylacetic acids under different Cu catalysts to give fused five-membered N-heterocycles or tertiary amides.

C-N bond formation via a copper-catalyzed aerobic oxidative decarboxylative tandem protocol was realized. The phenylacetic acids which contain ortho-X (X = F or Br) on the aromatic ring will render a fused five-membered heterocycle via a tandem aromatic nucleophilic substitution and aerobic oxidative decarboxylative acylation at the C(sp(2))-H bond of benzimidazoles under the Cu(OAc)2/K2CO3/BF3·Et2O catalytic system, while with CuBr as the catalyst and pyridine as the base, N-acylation occurred and tertiary amides were obtained.

Substituent-Controlled Chemoselective Cleavage of C═C or Csp(2)-C(CO) Bond in α,β-Unsaturated Carbonyl Compounds with H-Phosphonates Leading to β-Ketophosphonates.

An unprecedented substituent-controlled chemoselective cleavage of C═C double bond or C(sp(2))-C(CO) bond along with aerobic phosphorylation of α,β-unsaturated carbonyl compounds with H-phosphonates through a radical process has been disclosed. The current strategy provides an access to β-ketophosphonates under mild conditions with a wide substrate scope.

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles.

A copper-catalyzed oxidative direct formation of amides from nonactivated carboxylic acids and azoles with dioxygen as an activating reagent is reported. The azole amides were produced in good to excellent yields with a broad substrate scope. The mechanistic studies reveal that oxygen plays an essential role in the success of the amidation reactions with copper peroxycarboxylate as the key intermediate.