Cascade Sequence Research Articles

Minimizing undesirable load shedding through robust coordination of directional overcurrent relays

The directional overcurrent relay coordination is often performed taking into account the scenario in which the system is expected to operate most of the time. However, such an approach frequently lead to solutions that are not robust enough to deal with perturbed conditions (e.g., topology changes and line losses), which can cause a cascade sequence of unnecessary load disconnections. A new approach to improve the robustness of directional overcurrent relay coordination is presented in this work. At first, relay settings are found to the expected conditions, using a matheuristic algorithm based on Differential Evolution, Linear Programming, and local search techniques. Afterward, the solution found by the algorithm is used as an input on a re-optimization framework, in which protection must remain coordinated and fast, but undesirable load shedding is also minimized in single line dropping scenarios (N-1 criterion). The proposed approach is applied to four test cases: a real meshed network, IEEE-30 bus, IEEE-118 bus, and IEEE-300 bus. These systems have up to 590 relays and 1,044 primary/backup relations.

Porous Organic Polymer-Derived Nanopalladium Catalysts for Chemoselective Synthesis of Antitumor Benzofuro[2,3- b]pyrazine from 2-Bromophenol and Isonitriles.

An efficient strategy for the synthesis of benzofuro[2,3- b]pyrazines was developed. These tricyclic scaffolds were formed through a multistep cascade sequence, which includes double insertion of isonitriles and chemoselective bicyclization. In this reaction, a nanopalladium was used as a recyclable catalyst. Product 3w exhibited excellent anticancer activity toward T-24 (IC50 = 12.5 ± 0.9 μM) and HeLa (IC50 = 14.7 ± 1.6 μM) cells. We also explored the action mechanism of 3w on T-24 cells.

Stereoselective Synthesis of 1‐Arylpropan‐2‐amines from Allylbenzenes through a Wacker‐Tsuji Oxidation‐Biotransamination Sequential Process

AbstractHerein, a sequential and selective chemoenzymatic approach is described involving the metal‐catalysed Wacker‐Tsuji oxidation of allylbenzenes followed by the amine transaminase‐catalysed biotransamination of the resulting 1‐arylpropan‐2‐ones. Thus, a series of nine optically active 1‐arylpropan‐2‐amines were obtained with good to very high conversions (74–92%) and excellent selectivities (>99% enantiomeric excess) in aqueous medium.The Wacker‐Tsuji reaction has been exhaustively optimised searching for compatible conditions with the biotransamination experiments, using palladium(II) complexes as catalysts and iron(III) salts as terminal oxidants in aqueous media. The compatibility of palladium/iron systems for the chemical oxidation with commercially available and made in house amine transaminases was analysed, finding ideal conditions for the development of a general and stereoselective cascade sequence. Depending on the selectivity displayed by selected amine transaminase, it was possible to produce both 1‐arylpropan‐2‐amines enantiomers under mild reaction conditions, compounds that present therapeutic properties or can be employed as synthetic intermediates of chiral drugs from the amphetamine family.magnified image

Gold-Catalyzed Cascade Reactions of 4 H-Furo[3,2- b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives.

Merging the ability of cationic gold(I) catalysts to activate unsaturated π-systems with the electrophiles-driven ring-opening reactions of furans, we describe a new approach to synthesize 2-spiroindolin-3-ones from 4 H-furo[3,2- b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ring-opening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3 H-indolin-3-ones in moderate to good yields.

An Enzyme Cascade Synthesis of Vanillin

A novel approach for the synthesis of vanillin employing a three-step two-enzymatic cascade sequence is reported. Cytochrome P450 monooxygenases are known to catalyse the selective hydroxylation of aromatic compounds, which is one of the most challenging chemical reactions. A set of rationally designed variants of CYP102A1 (P450 BM3) from Bacillus megaterium at the amino acid positions 47, 51, 87, 328 and 437 was screened for conversion of the substrate 3-methylanisole to vanillyl alcohol via the intermediate product 4-methylguaiacol. Furthermore, a vanillyl alcohol oxidase (VAO) variant (F454Y) was selected as an alternative enzyme for the transformation of one of the intermediate compounds via vanillyl alcohol to vanillin. As a proof of concept, the bi-enzymatic three-step cascade conversion of 3-methylanisole to vanillin was successfully evaluated both in vitro and in vivo.

Bond Forming Reactions Involving Isocyanides at Diiron Complexes

The versatility of isocyanides (CNR) in organic chemistry has been tremendously enhanced by continuous advancement in transition metal catalysis. On the other hand, the urgent need for new and more sustainable synthetic strategies based on abundant and environmental-friendly metals are shifting the focus towards iron-assisted or iron-catalyzed reactions. Diiron complexes, taking advantage of peculiar activation modes and reaction profiles associated with multisite coordination, have the potential to compensate the lower activity of Fe compared to other transition metals, in order to activate CNR ligands. A number of reactions reported in the literature shows that diiron organometallic complexes can effectively assist and promote most of the “classic” isocyanide transformations, including CNR conversion into carbyne and carbene ligands, CNR insertion, and coupling reactions with other active molecular fragments in a cascade sequence. The aim is to evidence the potential offered by diiron coordination of isocyanides for the development of new and more sustainable synthetic strategies for the construction of complex molecular architectures.

Synthesis of (E)-α,β-unsaturated carboxylic esters derivatives from cyanoacetic acid via promiscuous enzyme-promoted cascade esterification/Knoevenagel reaction

A new enzymatic protocol based on lipase-catalyzed cascade toward (E)-α,β-unsaturated carboxylic esters is presented. The proposed methodology consists of elementary organic processes starting from acetals and cyanoacetic acid leading to the formation of desired products in a cascade sequence. The combination of enzyme promiscuous abilities gives a new opportunity to synthesize complex molecules in the one-pot procedure. Results of studies on the influence of an enzyme type, solvent, and temperature on the cascade reaction course are reported. The presented methodology provides meaningful qualities such as significantly simplified process, excellent E-selectivity of obtained products and recycling of a biocatalyst.

Photochemically Produced Aminocyclobutanes as Masked Dienes in Thermal Electrocyclic Cascade Reactions.

Cyclobutane products of a triplet sensitized enamide-alkene intramolecular [2 + 2] photocycloaddition have been shown to undergo fragmentation under acidic conditions. This lability has been exploited by inducing a complexity-generating thermal electrocyclic cascade sequence involving the in situ formation of a cyclobutene, followed by electrocyclic ring opening, Diels-Alder cycloaddition, and subsequent lactamization. This combination of excited state photochemistry and thermal electrocyclic cascade reactions allows simple planar molecules to be rapidly transformed into sp3-rich scaffolds.

A gold-triggered dearomative spirocarbocyclization/Diels-Alder reaction cascade towards diverse bridged N-heterocycles.

A rapid approach for the diversity-oriented synthesis of complex bridged polycyclic N-heterocycles from readily available starting materials in two operational steps has been developed. This strategy firstly introduces molecular diversity by an Ugi four-component reaction, and then achieves these bridged N-heterocycles via an efficient gold-triggered chemo- and diastereoselective cascade non-oxidative ortho-dearomative spirocarbocyclization/Diels-Alder reaction sequence. The application of microwave irradiation for this cascade process efficiently shortens the reaction time to 10 minutes and improves the diastereoselectivity.

Scalable Synthesis of Naphthothiophene and Benzodithiophene Scaffolds as π-Conjugated Synthons for Organic Materials

The synthesis on a gram-scale and the full characterization of naphtho[1,2-b]thiophene and benzo[1,2-b:6,5-b']dithiophene 4-carboxylate esters bearing 2-octyldodecyl side chains, and their stannylated and brominated derivatives, suitable for their insertion into π-conjugated polymers is described. The fully soluble and processable synthons are obtained through a cascade sequence of reactions, namely direct arylation and cross aldol condensation, which create an effective pathway for the annulation and π-extension of suitable, commercially available reagents. The newly reported synthesis are compared, whenever possible, using ‘green chemistry metrics’ with literature synthesis, showing dramatic improvements.

Access to 3‐(2‐Oxoalkyl)‐azaspiro[4.5]trienones via Acid‐Triggered Oxidative Cascade Reaction through Alkenyl Peroxide Radical Intermediate

AbstractAzaspiro[4.5]trienones bearing ketone side chains at the 3‐position are prepared from N‐alkyl‐arylpropiolamides and ketones via oxidative 1,2‐difunctionalization of alkynes. The cascade sequence starts with the generation of alkenyl peroxide intermediates, which are obtained by addition of tert‐butyl hydroperoxide to ketones in presence of a catalytic amount of a strong acid. Then, the ketone radical adds to alkynes, followed by spirocyclization and dearomatization process. This method represents a new example of difunctionalization of alkynes with simultaneous formation of two carbon−carbon single bonds and one carbon−oxygen double bond in one step.magnified image

Formal Total Synthesis of Hybocarpone Enabled by Visible-Light-Promoted Benzannulation.

The formal total synthesis of hybocarpone was achieved in eight steps from commercially available 1,2,4-trimethoxybenzene. Key transformations include a visible-light-promoted benzannulation to construct the key α-naphthol intermediate and a modified CAN-mediated dimerization/hydration cascade sequence to generate the vicinal all-carbon quaternary centers in a stereocontrolled manner. The total synthesis of boryquinone was also achieved in seven steps.

Stereoselective Synthesis of Diverse Lactones through a Cascade Reaction of Rhodium Carbenoids with Ketoacids.

A convergent cascade approach for the stereoselective synthesis of diverse lactones is described. The Rh2(TFA)4-catalyzed cascade reaction proceeds via a carboxylic acid O-H insertion/aldol cyclization with high chemo-, regio-, and diastereoselectivity. The cascade reaction provides quick access to highly functionalized γ-butyro- and δ-valerolactones from readily accessible ketoacid and diazo synthons. To demonstrate the utility of this approach, a thermally induced oxy-Cope ring-expansion strategy has been incorporated in the cascade sequence to access medium-sized lactones, which can undergo a serendipitous rearrangement to form spiro-lactones through an intramolecular aldol/trans-lactonization sequence. The reaction has proven to be general, with a range of ketoacids and diazo carbonyls to provide functionalized lactones of varying ring sizes.

Transition-Metal-Free, Brønsted Acid-Mediated Cascade Sequence in the Reaction of Propargyl Alcohols with Sulfonamido-indoles/-indolines: Highly Substituted δ- and α-Carbolines.

Brønsted acid-mediated, transition-metal-free reaction of propargyl alcohols with sulfonamido-indoles/-indolines under mild conditions affords highly substituted δ- or α-carbolines in good to excellent yields. This protocol involves cascade reaction sequences of Friedel-Crafts alkylation/ [1,5]-hydrogen shift/electrocyclization/elimination/ [1,2]-aryl migration followed by aromatization. An unexpected regioselective tosyl group migration from indole 2- to 6-position and arene elimination leading to α-carbolines has also been discovered.

Scalable Synthesis of Naphthothiophene-based D-π-D Extended Oligomers through Cascade Direct Arylation Processes

The synthesis of two novel π-extended oligomers, incorporating naphtho[1,2-b]thiophene-4-carboxylate 2-octyldodecyl esters as end-capping moieties, and two different conjugated core fragments, has been achieved through a cascade sequence of sustainable organic reactions. Benzo[c][1,2,5]thiadiazole and 2-octyldodecyl benzo[1,2-b:6,5-b′]dithiophene-4-carboxylate have been used, respectively, as electron-poor and electro-rich π-conjugated cores. In the latter case, a sequence of nine aromatic rings in a fully conjugated structure is achieved with a high yielding, sustainable cascade approach. The optoelectronic properties of both oligomers are reported.

Cascade Synthesis of Benzothieno[3,2- b]indoles under Oxidative Conditions Mediated by CuBr and tert-Butyl Hydroperoxide.

A series of biologically relevant compounds of benzothieno[3,2- b]indole derivatives were conveniently synthesized from reactions of N-protected 2-((2-bromophenyl)ethynyl)anilines and potassium ethylxanthate, mediated by cuprous bromide/ tert-butyl hydroperoxide. The method features the construction of the pyrrole and thiophene rings in a cascade sequence with the pyrrole ring being formed prior to the thiophene ring via a possible reactive Cu(III)-pyrrole intermediate.

Pd(II)-Catalyzed [4 + 2] Heterocyclization Sequence for Polyheterocycle Generation.

A new Pd(II)-catalyzed cascade sequence for the formation of polyheterocycles, from simple starting materials, is reported. The sequence is applicable to both indole and pyrrole substrates, and a range of substituents are tolerated. The reaction is thought to proceed by a Pd(II)-catalyzed C-H activated Heck reaction followed by a second Pd(II)-catalyzed aza-Wacker reaction with two Cu(II)-mediated Pd(0) turnovers per sequence. The sequence can be considered a formal [4 + 2] heterocyclization.

Copper-Catalyzed Synthesis of Substituted 4-Acylpyrazole Derivatives through a Cascade Transformation from N-Propargylic Sulfonylhydrazones and Diaryliodonium Salts

A concise strategy for the synthesis of substituted 4-acylpyrazole derivatives from N-propargylic sulfonylhydrazones and diaryliodonium salts has been developed. The pyrazole derivatives are formed through a five-step cascade sequence that includes intramolecular cyclization, hydroxylation, elimination, copper-catalyzed aerobic oxidation, and intramolecular rearrangement.

Chemoselective one-pot access to benzo[e]indole-4,5-diones and naphtho[2,1-b]thiophene-4,5-diones via copper-catalyzed oxidative [3 + 2] annulation of α-oxoketene N,S-acetals/β-ketothioamides with α-/β-naphthols

An operationally simple and efficient one-pot method for the synthesis of 1-aroyl (or alkanoyl)-2-thioalkyl-3-aryl (or alkyl)-3H-benzo[e]indole-4,5-diones and naphtho[2,1-b]thiophene-4,5-diones has been devised by copper-catalyzed cross-coupling of α-oxoketene N,S-acetals/β-ketothioamides with α-/β-naphthols in open air for the first time. The key to the success of this transformation is the room temperature oxidation of α-/β-naphthol to 1,2-naphthoquinone as a reactive species, which undergoes formal [3 + 2] annulation with α-oxoketene N,S-acetals/β-ketothioamides via cascade sequence of Michael addition/tautomerization/oxidation/cyclization/aromatization reactions, enabling addition of a pyrrole/thiophene ring onto naphthoquinone moiety. Further, benzo[e]indole-4,5-diones were transformed to pentacyclic fused phenazine derivatives under solvent-free conditions. Based on our experimental outcomes, a tentative mechanistic rationale for this chemoselective protocol is proposed, which is well validated and supported by the control experiments.

Metal-Free One-Pot Four-Component Cascade Annulation in Ionic Liquids at Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives.

An efficient, eco-friendly, and highly convergent one-pot route to privileged thiazoloquinolinone derivatives has been developed via four-component cascade coupling (4CCC) of α-enolic dithioesters, cysteamine/2-aminothiophenols, aldehydes, and cyclic 1,3-diketones in recyclable [EMIM][EtSO4] ionic liquid at room temperature for the first time. The reaction proceeds via a N,S-acetal formation, Knoevenagel condensation, aza-ene reaction, imine-enamine/keto-enol tautomerization, and intramolecular N-cyclization cascade sequence. The merit of the protocol is highlighted by its efficacy of forming consecutive five new bonds (two C-C, two C-N, and one C-S) and two rings with all reactants being efficiently utilized. The operational simplicity, sustainability, mild conditions, excellent yields, tolerance of wide functional groups, and avoidance of expensive/toxic reagents are additional attributes to this domino four-component protocol. Notably, the products were easily separated from the ionic liquid, and thus the ionic liquid obtained was reused four times without considerable loss of any activity.