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Efficient copper-catalyzed [3 + 2] cycloadditions of ethynyl indoloxazolidones with 1,3-cyclohexanediones to access functionalized furan derivatives under mild conditions.

The visible-light-promoted difunctionalization of alkenyl ketones has been developed for easy access of various tetralones, cyclopropane, or alkenyl migration compounds. With

Controlling absolute stereochemistry in catalytic photochemical reactions is generally challenging owing to high rates of background reactivity. Successful strategies broadly rely on selective excitation of the reaction substrate when associated with a chiral catalyst. Recent studies have demonstrated that chiral Lewis acid complexes can enable selective energy transfer from a photosensitizer to facilitate enantioselective triplet state reactions. Here, we apply this approach to the enantioselective catalysis of a 6π photocyclization through the design of an iridium photosensitizer optimized to undergo energy transfer to a reaction substrate only in the presence of a chiral Lewis acid complex. Among a group of iridium(III) sensitizers, enantioselectivity and yield closely correlate with photocatalyst triplet energy within a narrow window enabled by a modest reduction in substrate triplet energy upon binding a scandium/ligand complex. These results demonstrate that photocatalyst tuning offers a means to suppress background reactivity and improve enantioselectivity in photochemical reactions.

An acid-catalyzed formal [3 + 2] cyclization/N,O-ketalization of in situ formed ortho-alkynyl quinone methides (o-AQMs) and tryptophol derivatives was developed.

Herein, we present a palladium-catalyzed tandem [4+1] cyclo­addition of 4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-ones with ­N-tosyl­hydrazones. The reaction is accomplished by merging the in situ generated aza-ortho-quinone methides (aza-o-QMs) with nucleophilic carbenes. This method enables the construction of diverse indolines with broad functional group compatibility in good yields with high levels of diastereoselectivity under mild conditions.

Controlling absolute stereochemistry in catalytic photochemical reactions is generally challenging owing to high rates of background reactivity. Successful strategies broadly rely on selective excitation of the reaction substrate when associated with a chiral catalyst. Recent stud-ies have demonstrated that chiral Lewis acid complexes can enable selective energy transfer from a photosensitizer to facilitate enantiose-lective triplet state reactions. Here, we apply this approach to the enantioselective catalysis of a 6π photocyclization through the design of an iridium photosensitizer optimized to undergo energy transfer to a reaction substrate only in the presence of a chiral Lewis acid complex. Amongst a group of iridium(III) sensitizers, enantioselectivity and yield closely correlate with photocatalyst triplet energy within a narrow window enabled by a modest reduction in substrate triplet energy upon binding a scandium/ligand complex. These results demonstrate that photocatalyst tuning offers a means to suppress background reactivity and improve enantioselectivity in photochemical reactions.

Herein, we describe a highly effective 1,8-conjugate-addition-mediated formal (3+3)-annulation of (aza)-para-quinone methides in situ generated from propargylic alcohols with 4-hydroxycoumarins and 1,3-dicarbonyl compounds under the catalysis of a Bronsted acid. This methodology affords efficient and practical access to synthetically important and highly functionalized pyranocoumarins and pyrans in excellent yields under mild conditions. Importantly, these products exhibit impressive inhibitory activity toward α-glucosidase.

Herein, we report an efficient Bronsted acid-catalyzed formal (3+3)-annulation of (aza)-para-quinone methides generated in situ from propargylic alcohols with naphthol derivatives, which involves a 1,8-conjugate addition/6-endo annulation process. This protocol provides an effective method for preparing important functionalized pyranocoumarins under mild conditions.

An efficient and straightforward Brønsted acid mediated (3+2)-annulation of (aza)-para-quinone methides, generated in situ from propargylic alcohols and indoles, has been developed involving 1,8-conjugate addition/5-endo annulation cascade. This protocol affords a mild and effective method for the construction of synthetically important and structurally interesting functionalized pyrrolo[1,2-a]indoles.

An efficient and straightforward Lewis-acid-mediated stereoselective (4 + 3)-cyclization of indole-substituted alkylidene malonates and donor-acceptor cyclopropanes has been developed involving the Friedel-Crafts/Michael addition cyclization cascade. This reaction provides a mild and effective method for the construction of synthetically and structurally interesting functionalized cycloheptannelated indoles.

A novel visible-light photoredox catalysis protocol for the effective and efficient synthesis of 3-substituted chroman-4-ones and 2,3-dihydroquinolin-4(1H)-ones via tandem radical addition/cyclization of alkenyl aldehydes has been described. This reaction features a broad substrate scope, mild reaction conditions, and good functional group tolerance character.

Attempts to the construction of B/C ring and E ring in melotenine A are described. Based on para-dienone chemistry, a tactical application of tandem aminolysis/aza-Michael addition reaction was made to access highly functionalized building blocks with the pyrrolo[2,3-d]carbazole tetracyclic unit (A/B/C/D ring). Albeit negative results for assembling the dihydroazepine unit (E ring) by using the proposed fragmentation reaction of gem-dihalocyclopropanes, an alternative strategy based on ring closing metathesis was evolved to forge the E ring possessing a twisted 1,3-diene unit embedded in the rigid skeleton of melotenine A.

A new series of 4-carboxybenzenesulfonamide organotin(IV) complexes, [Me3Sn(O2CC6H4-SO2NH2-4)] (1), [n-Bu3Sn(O2CC6H4-SO2NH2-4)] (2), [Ph3Sn(O2CC6H4-SO2NH2-4)] (3), [(Me2Sn)4(μ3-O)2(μ2-OCH3)2(O2CC6H4-SO2NH2-4)2] (4), [(n-Bu2Sn)4(μ3-O)2(μ2-OCH3)2(O2CC6H4-SO2NH2-4)2] (5), [(n-Oct2Sn)4(μ3-O)2(μ2-OCH3)2(O2CC6H4-SO2NH2-4)2] (6), have been designed and synthesized from the reactions of 4-carboxybenzenesulfonamide with the corresponding triorganotin(IV) chloride or diorganotin(IV) oxide. The six complexes were characterized by elemental analysis, FT-IR, NMR (1H, 13C and 119Sn) spectroscopy, as well as by single crystal X-ray diffraction analysis. X-ray diffraction discloses that complexes 1–3 represent mononuclear tin(IV) monomer, and complexes 4–6 adopt tetranuclear tin(IV) ladder-like structure containing two deprotonated ligands linked by three alternate Sn2O2 four-membered rings. Analysis of the non-covalent intermolecular contacts in all complexes reveals the existence of the N H⋯O C, N H⋯O S and Sn⋯O interactions, which play significant function in the supramolecular construction. Furthermore, complexes 1–5 were evaluated for their in vitro cytostatic activity against human cervical carcinoma cell lines (HeLa) and human hepatocellular carcinoma cell lines (HepG-2). The pilot study has confirmed that some of these novel organotin(IV) complexes exhibited high in vitro cytostatic activity.

Peroxynitrite (ONOO−) is closely related to various physiological and pathological processes. Real-time, selective, and sensitive detection of ONOO− is of great importance. Based on the intramolecular charge transfer (ICT) mechanism, a novel near-infrared (NIR) and naked-eye fluorescence probe DCIPP was developed with “turn-on” fluorescence properties for monitoring ONOO− in living cells. The probe DCIPP is composed of a dicyanoisophorone electron-accepting scaffold and a reactive electron-drawing diphenyl phosphoryl group for imaging ONOO−. Upon addition of ONOO−, the fluorescence intensity of DCIPP is enhanced obviously at 665 nm in emission spectra, and the colour of DCIPP solution changes from pale yellow to purple at the same time. Based on the nucleophilic propensity of ONOO−, this probe displays highly selective detection of ONOO− over other various bioactive molecules and could quantitatively and sensitively detect ONOO− with a low limit of detection (LOD) of 33 nM by the fluorescence method and 0.29 μM by the UV method. Moreover, DCIPP was successfully applied to the fluorescence imaging of ONOO− in living cells and zebrafish with good cell-membrane permeability and low cytotoxicity.

A Lewis acid-catalyzed one-pot aza-Michael addition/fragmentation/sulfinyl conjugate addition/cyclization cascade of o-QMs and arylsulfonyl hydrazides is described for the first time. This technology engages a broad range of substrates with both components under mild conditions, giving the corresponding valuable 3-sulfonylbenzofurans in generally good yields. These investigations show the use of arylsulfonyl hydrazides as nucleophiles for the first time in catalytic C–N and C–S bond formation with o-QMs.

Herein, we describe a highly effective 1,8-conjugate-addition-mediated formal (3+3)-annulation of (aza)

Herein, we report an efficient Brønsted acid-catalyzed formal (3+3)-annulation of (aza)

Asymmetric conjugate addition of PhMe2SiBPin to a wide range of N-heteroaryl alkenes proceeded in the presence of a copper catalyst coordinated with an easily accessible chiral phosphoramidite ligand to afford useful β-silyl N-heteroarenes in high yields (up to 96%) and excellent enantioselectivities (up to 97% ee).

A versatile Lewis acid catalyzed tandem cyclization of in situ generated alkynyl o-quinone methides ( o-AQMs) with electron-rich phenols has been developed on the basis of the mode involving an intermolecular 1,4-conjugate addition/6-endo cyclization/1,3-aryl shift/intramolecular 1,4-conjugate addition cascade. This reaction provides a new method for expeditious assembly of synthetically and biologically interesting tetracyclic bridged dioxabicyclo[3.3.1]nonane skeletons featuring a congested bridgehead oxa-quaternary stereocenter.

Four new p-aminobenzenesulfonate organotin complexes, [(n-Bu3Sn)(O3SC6H3-NH2-4)]n (1), [(n-Bu2Sn)4(O)2(OH)2(O3SC6H4-NH2-4)2] (2), [(Me2Sn)4(O)2(OH)2(O3SC6H4-NH2-4)2] (3) and [{(n-BuSn)12O14(OH)6}(O3SC6H4-NH2-4)2·3C4H8O2] (4·diox), were synthesized by reaction of p-aminobenzenesulfonic acid with tributyltin oxide, dibutyltin oxide, dimethyltin oxide and monobutyltin oxide, respectively. These complexes were characterized by elemental analysis, FT-IR, NMR (1H, 13C, 119Sn) spectroscopy as well as single-crystal X-ray diffraction. The crystal structure of complex 1 reveals that it is a 1D zig-zag chain structure and further interlinked into a 2D network by intermolecular interaction (N-H⋯O). The structure analysis indicates that complexes 2 and 3 are the ladder-like structure including three alternate Sn2O2 rings, and further result in the formation of a 3D supramolecular architecture for 2 and a 2D supramolecular network for 3 by extensive hydrogen-bonding interactions (O-H⋯O, N-H⋯O). Complex 4 exhibits a dodecanuclear organooxotin cages, which are connected into a hydrogen-bonded 2D structure. Furthermore, complexes 1-4 were evaluated for their in vitro cytostatic activity against the human lung cancer cells (A549) and the human hepatocellular carcinoma cells (HepG-2). The preliminary screen shows that organotin derivatives with increasing number n-butyl group exhibitsignificantly higher cytostatic activity, and much higher than methyl group.

Hydrophosphorylated fullerene derivatives were readily prepared in one step by treating C60 with Ph3– n PCl n (n = 1–3) and ROH (R = H, alkyl). The one-pot reaction could be performed under mild conditions with moderate to good yields. Dichlorophenylphosphine and alcohols exhibited unexpected reactivity towards C60. A possible reaction mechanism involving the formation of P(III)–OH in situ was proposed to explain the experimental results.

The first total syntheses of Lycopodium alkaloids palhinine A, palhinine D, and their C3-epimers have been divergently achieved through the use of a connective transform to access a pivotal hexacyclic isoxazolidine precursor. A microwave-assisted regio- and stereoselective intramolecular nitrone-alkene cycloaddition was tactically orchestrated as a key step to install the crucial 10-oxa-1-azabicyclo[5.2.1]decane moiety embedded in the conformationally rigid isotwistane framework, demonstrating the feasibility of constructing the highly strained medium-sized ring by introduction of an oxygen bridging linker to relieve the transannular strain in the polycyclic scaffold. Subsequent N-O bond cleavage provided the synthetically challenging nine-membered azonane ring system bearing the requisite C3 hydroxyl group. Late-stage transformations featuring a chemo- and stereoselective reduction of the pentacyclic β-diketone secured the availability of our target molecules.

A novel Lewis base-catalyzed [4 + 3] annulation process for the construction of benzo[b]oxepine scaffolds has been developed. 1,4-Diazabicyclo[2.2.2]octane (DABCO) promotes the union of o-QMs and Morita–Baylis–Hillman carbonates in reasonable to excellent yields and good stereoselectivities (dr > 20:1). This straightforward, catalytic approach offers access to a variety of synthetically useful benzo[b]oxepine derivatives bearing oxindole scaffolds containing all-carbon spiro-quaternary stereocenters.

A novel metal-free one-pot protocol for the effective and efficient synthesis of 3-phosphinoylbenzofurans via a phospha-Michael addition/cyclization of H-phosphine oxides and in situ generated ortho-quinone methides is described. Based on the expeditious construction of C(sp2)–P bonds, asymmetric synthesis of optically pure 3-phosphinoylbenzofurans containing chiral P-stereogenic center has also been probed by using chiral RP-(−)-menthyl phenylphosphine oxide.

Resulting from the drastic increase of atmospheric CO 2 concentration day by day, global warming has become a serious environmental issue nowadays. The fixation of CO 2 to obtain desirable, economically competitive chemicals has recently received considerable attention. This work investigates the fixation of CO 2 along with three bromopyridines via a facile electrochemical method using a silver cathode to synthesize picolinic acids, which are important industrial and fine chemicals. Cyclic voltammetry is employed to investigate the cyclic voltammetric behaviour of bromopyridines. In addition, systematic study is conducted to study the relationships between the picolinic acids' yield and the electrolysis conditions and intrinsic parameters. The results show that the target picolinic acids' yields are strongly dependent on various conditions such as solvent, supporting electrolyte, current density, cathode material, charge passed, temperature and the nature of the substrates. Moreover, in the studied electrode materials such as Ag, Ni, Ti, Pt and GC, electrolysis and cyclic voltammetry show that Ag has a good electrocatalytic effect on the reduction and carboxylation of bromopyridine. This facile electrochemical route for fixation of CO 2 provides an indispensable reference for the conversion and utilization of CO 2 under mild conditions.

An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization. A unified strategy based on this key tandem methodology has been divergently explored for the asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)-deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich the tandem reaction design concerning the asymmetric catalytic assembly of a chiral all-carbon quaternary stereocenter contained in the densely functionalized hydrocarbazole synthons but also manifest the potential for the application of the asymmetric catalysis based on the para-dienone chemistry in asymmetric synthesis of natural products.

A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl esters has been developed, providing a new method for expeditious assembly of synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based on this key annulation, strategic installation of the pivotal azaspirocyclic core, followed by constructing the benzazepine unit via Witkop cyclization, led to the divergent total syntheses of cephalotaxine and cephalezomine H.

Lycopodium alkaloids with structural diversity and biological significance have been stimulating an increasing interest in the synthetic and medicinal communities, in which inspiration and exploration of their related biogenetic relationship generally constitute one of the major concerns. Driven by the plausible biogenetic entry to lycojaponicumin D as the first member of Lycopodium alkaloids having a structurally unusual C3-C13-linked scaffold, a new connection with lycodoline has been proposed and discovered on the basis of the design of an unprecedented bioinspired tandem fragmentation/Mannich reaction. Initiated by expeditious assembly of bridgehead heterofunctionalization in the [3.3.1] bicyclic system of lycodoline, a novel tandem palladium-mediated oxidative dehydrogenation/hetero-Michael reaction has been developed for the strain-driven formation of the C-heteroatom bond, leading to a new approach to conformationally rigid bridgehead heteroquaternary carbons. The present unified strategy provides a scenario for the divergent total syntheses of nine natural Lycopodium alkaloids and four unnatural C12 epimers, wherein (±)-lycojaponicumin D and six lycodoline-type alkaloids have been synthetically achieved for the first time.

An oxidative dearomatizing cyclization of arylamines promoted by iodobenzene bis(trifluoroacetate) [PhI(CF3CO2)(2)] has been explored, leading to a novel synthetic approach to functionalized spirocyclic building blocks containing the structurally unique dieniminium moiety. This unprecedented methodology, featuring oxidative dearomatization and carbon-carbon bond-forming cyclization, to some extent, not only expands the synthetic potential of hypervalent iodine chemistry, but also enriches the oxidation chemistry of arylamines.

Cat. on a hot tin roof: Enantioselective catalytic Michael addition of α-cyanoketones to acrylates under bifunctional organocatalysis was used to construct the unique arylic all-carbon quaternary stereocenter, which is synthetically crucial in the chemical synthesis of optically pure cis-aryl hydroindole alkaloids. The protocol offers an asymmetric route to (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine.

A novel DBU-mediated stereoselective spirocyclopropanation of para-quinone methides with sulfonium salts has been developed on the basis of the mode involving a 1,6-conjugate addition/intramolecular dearomatizing cyclization cascade. This reaction provides a mild and effective method for the assembly of synthetically and structurally interesting spirocyclopropanyl para-dienones. The feasibility for the enantioselective access to such functionalized para-dienones has also been explored by using the axially chiral sulfonium salt. Importantly, the regioselective ring openings of the related spirocyclopropanyl para-dienones have been achieved divergently.

The asymmetric catalytic 1,6-addition of p-QMs with racemic oxindoles under the bifunctional catalysis of C2-symmetric dimeric Cinchona-derived squaramide is described. This tertiary amine-squaramide catalyzed reaction provides a diastereoselective and enantioselective approach to the effective assembly of diverse diarylmethine-substituted oxindoles having vicinal tertiary and quaternary stereocenters.

The asymmetric catalytic 1,6-addition of p-QMs with racemic oxindoles under the bifunctional catalysis of C2-symmetric dimeric Cinchona-derived squaramide is described. This tertiary amine-squaramide catalyzed reaction provides a diastereoselective and enantioselective approach to the effective assembly of diverse diarylmethine-substituted oxindoles having vicinal tertiary and quaternary stereocenters.

A novel DBU-mediated stereoselective spirocyclopropanation of para-quinone methides with sulfonium salts has been developed on the basis of the mode involving a 1,6-conjugate addition/intramolecular dearomatizing cyclization cascade. This reaction provides a mild and effective method for the assembly of synthetically and structurally interesting spirocyclopropanyl para-dienones. The feasibility for the enantioselective access to such functionalized para-dienones has also been explored by using the axially chiral sulfonium salt. Importantly, the regioselective ring openings of the related spirocyclopropanyl para-dienones have been achieved divergently.

The synthetically useful functionalized 2-substituted piperidines containing a lateral ketone group have been strategically accessed via an organocatalytic enantioselective intramolecular aza-Michael addition of enone carbamates, in which a novel internal substrate combination of the enone moiety as Michael acceptor and the carbamate moiety as Michael donor was revealed in asymmetric bifunctional organocatalysis. This heteroatom conjugate addition, which was realized by using a catalytic chiral Cinchona-based primary-tertiary diamine and an achiral Bronsted acid, mostly proceeded in high yield and good to excellent stereocontrol (up to 99% ee). This reaction provides an alternative catalytic asymmetric method for installing the stereogenic nitrogen-containing carbon center in functionalized 2-substituted piperidines, leading to the development of a straightforward and expeditious synthesis of some naturally occurring bioactive 2-substituted piperidine alkaloids.

An unprecedented asymmetric tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides [e.g. (I)] with the formation of the chiral quaternary center in the densely functionalized hydrocarbazole synthons [e.g. (III)] is studied.

An oxidative dearomatizing cyclization of arylamines promoted by iodobenzene bis(trifluoroacetate) [PhI(CF3CO2)(2)] has been explored, leading to a novel synthetic approach to functionalized spirocyclic building blocks containing the structurally unique dieniminium moiety. This unprecedented methodology, featuring oxidative dearomatization and carbon-carbon bond-forming cyclization, to some extent, not only expands the synthetic potential of hypervalent iodine chemistry, but also enriches the oxidation chemistry of arylamines.

The pain ends here: A novel synthetic strategy for the construction of (±)-morphine rings B and E was developed, in which SmI2 -promoted reductive coupling/desulfurization and tandem alcoholysis/oxa-Michael addition featured as the key steps for the assembly of the C9-C14 and C5-O bonds, respectively. Asymmetric tandem alcoholysis/oxa-Michael addition was also feasible for the enantiocontrolled synthesis of morphine.

The stereoselective, expedient assembly of the key functionalized isotwistane (bridged tricyclo[4.3.1.0(3,7)]decane) system, 5/6/6 ring, with contiguous quaternary stereocenters in Lycopodium alkaloid palhinine A and its analogues via an intramolecular Diels-Alder strategy is described.

A new, highly enantioselective approach to a number of 2-functionalized piperidines as well as pyrrolidines and oxazolidines is reported.