Arylative Cyclization Research Articles

Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones via tandem arylative cyclization.

The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.

Access to chiral cyano-containing five-membered rings through enantioconvergent rhodium-catalyzed cascade cyclization of a diastereoisomeric E/Z mixture of 1,6-enynes

In contrast to the intermolecular rhodium-catalyzed asymmetric 1,4-addition of organometallic reagents to activated alkenes, the asymmetric arylative cyclization of a diastereoisomeric E/Z mixture of 1,6-enynes afforded only one major enantiomer.

3D Coumarin Systems Based on [2.2]Paracyclophane: Synthesis, Spectroscopic Characterization, and Chiroptical Properties.

In this article, we report the preparation of a series of [2.2]paracyclophane-fused coumarin systems through a simple and general procedure involving a transition-metal-catalyzed cyclization of aryl alkynoates as the key step. We also highlight the influence of the [2.2]paracyclophane (pCp) motif and its "phane" interactions on the spectroscopic properties of the newly synthesized fluorophores, which emit in the blue-green region of the visible spectrum (λem up to 560 nm) and show extremely large Stokes shifts (up to 230 nm). Finally, we demonstrate that our straightforward approach can easily be used to access optically active planar chiral 3D coumarins. Compared to previously described fluorescent paracyclophanes and other organic dyes, our compact heteroaromatic derivatives show promising chiroptical properties, both in term of circular dichroism ( gabs ∼ 8 × 10 -3) and circularly polarized luminescence ( glum ∼ 5 × 10 -3), thus demonstrating a practical application of our synthetic method.

First Report on the Validated Classification-Based Chemometric Modeling of Human Rhinovirus 3C Protease (HRV 3Cpro) Inhibitors

Human rhinoviruses (HRVs), a major cause of common cold and upper respiratory infections, may trigger severe respiratory complications like asthma and COPD. To date, no drugs are available in the market which are designed as novel HRV inhibitors despite the involvement of some pharmaceutical companies' due to economical and clinical constraints. HRV 3C protease may be a potential target for drug design as it plays crucial role in viral RNA replication and virion assembly process. Therefore, designing novel HRV 3Cpro inhibitors is necessary and demanding in the field of antiviral drug design. In this article, statistically significant and validated classification-based QSARs of a series of HRV 3Cpro inhibitors were performed for the first time as per the authors' knowledge. Results suggest that oxopyrrolidine and piperidinone rings are favored whereas carboxybenzyl and unsubstituted benzyl functions may be unfavorable. Moreover, this group, along with cyclic alkyl or aryl ring structures may favor HRV 3Cpro inhibition. These observations may be utilized for the design of a higher active anti-HRV agent in future.

Enantioselective Synthesis of Chiral Cyclopent-2-enones by Nickel-Catalyzed Desymmetrization of Malonate Esters.

The enantioselective synthesis of highly functionalized chiral cyclopent‐2‐enones by the reaction of alkynyl malonate esters with arylboronic acids is described. These desymmetrizing arylative cyclizations are catalyzed by a chiral phosphinooxazoline/nickel complex, and cyclization is enabled by the reversible E/Z isomerization of alkenylnickel species. The general methodology is also applicable to the synthesis of 1,6‐dihydropyridin‐3(2H)‐ones.

Induced secondary metabolites from the endophytic fungus Aspergillus versicolor through bacterial co-culture and OSMAC approaches

Two new cryptic 3,4-dihydronaphthalen-(2H)-1-one (1-tetralone) derivatives, aspvanicin A (1) and its epimer aspvanicin B (2), as well as several known cryptic metabolites (3–8), were obtained from the ethyl acetate extract of the co-culture of the endophytic fungus Aspergillus versicolor KU258497 with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium. When A. versicolor was cultured axenically in liquid Wickerham medium supplemented with 3.5% DMSO, an additional three known secondary metabolites (9–11) were isolated that were lacking when the fungus was fermented on rice medium. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopy as well as HRESIMS. The relative and absolute configurations of 1 and 2 were determined by the combination of NMR and electronic circular dichroism (ECD) analysis aided by DFT conformational analysis and TDDFT-ECD calculations. The ECD calculations revealed that although the sign of the blue-shifted overlapping n-π∗ ECD transition follows the helicity rule of cyclic aryl ketones, the calculation of low-energy conformers and ECD spectra was necessary to determine the stereochemistry. All metabolites were assessed for their antibacterial and cytotoxic activities; one of the new diastereomers, compound 2, showed moderate cytotoxic activity against the mouse lymphoma cell line L5178Y.

Synthesis of 2,3-Disubstituted Indoles by Alkylative and Arylative Cyclization of 2-Alkenylphenylisocyanides with Grignard Reagents

Synthesis of 2,3-Disubstituted Indoles by Alkylative and Arylative Cyclization of 2-Alkenylphenylisocyanides with Grignard Reagents

Synthesis of multisubstituted pyrroles by nickel-catalyzed arylative cyclizations of N-tosyl alkynamides.

The synthesis of multisubstituted pyrroles by the nickel-catalyzed reaction of N-tosyl alkynamides with arylboronic acids is reported. These reactions are triggered by alkyne arylnickelation, followed by cyclization of the resulting alkenylnickel species onto the amide. The reversible E/Z isomerization of the alkenylnickel species is critical for cyclization. This method was applied to the synthesis of pyrroles that are precursors to BODIPY derivatives and a biologically active compound.

Gold promoted arylative cyclization of alkynoic acids with arenediazonium salts.

Alkynoic acids derived from salicylic acid and analogues undergo arylative cyclization with arenediazonium salts promoted by gold in the absence of external ligands. The reaction is thermally induced and proceeds even in the absence of light. A difference in regioselectivity has been found compared with that observed in the cycloisomerization process of the same type of compounds.

Part II: Diastereoselective Reactions Involving β‐Mono‐ and β,β′‐Disubstituted Alkylidene Oxindoles: Pondering Alkene Geometry

AbstractPart II encompasses synthetic efforts towards the construction of acyclic and cyclic structures that contain carbon and heteroatoms by employing diastereoselective reactions of β,β′‐disubstituted alkylidene oxindole as the primary substrate. In addition to the construction of acyclic structures, carbocyclic and heterocyclic rings that contain three‐, five‐, six‐, and seven‐membered spirocycles or fused‐rings are also described. A few examples of the arylative cyclization of dienes have also been presented.

Arylative Cyclization of Indole‐1‐carboxamides with 1,6‐Enynes for the Synthesis of Polycyclic Indole Scaffolds

A new alkyne annulation strategy has been developed for the synthesis of polycyclic indole derivatives through a cascade of C–H annulation and Michael addition reactions. This is the first report on sequential alkyne annulation and aza‐Michael addition reactions of indole‐1‐carboxamides with alkyne tethered substrates.

Nickel‐Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines

AbstractA nickel‐catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium‐catalyzed process in that the nickel–carbon bond is converted into a C−H bond to release the product through protonation instead of hydride donation followed by C−H reductive elimination on Pd.

Nickel-Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines.

A nickel-catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium-catalyzed process in that the nickel-carbon bond is converted into a C-H bond to release the product through protonation instead of hydride donation followed by C-H reductive elimination on Pd.

Cationic Pd(II)-catalyzed arylative cyclization of 1,6-enynes with arylboronic acids

A cationic Pd(II)-catalyzed redox neutral arylative cyclization of enynes by using β-acetoxy elimination as the quenching step has been developed. The reaction offers an efficient method to access a variety of carbocycles and N-heterocycles bearing an exocyclic double bond.

Enantioselective Nickel-Catalyzed Intramolecular Allylic Alkenylations Enabled by Reversible Alkenylnickel E/Z Isomerization.

Enantioselective nickel‐catalyzed arylative cyclizations of substrates containing a Z‐allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza‐ and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions.

Enantioselective Nickel‐Catalyzed Intramolecular Allylic Alkenylations Enabled by Reversible Alkenylnickel E/Z Isomerization

AbstractEnantioselective nickel‐catalyzed arylative cyclizations of substrates containing a Z‐allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza‐ and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions.

Cationic Pd(II)-catalyzed arylative cyclization of N-(2-formylaryl)alkynamides: An efficient route to 2-quinolinones

A cationic palladium complex catalyzed arylative cyclization reaction of N-(2-formylaryl)alkynamides with arylboronic acids was developed. This new process provides an efficient way for the synthesis of functionalized 2-quinolinones in good to excellent yields under mild conditions. Some control experiments were conducted to explain the possible mechanism for the formation of the products.

Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds.

A novel and efficient tandem SN2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc)3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

Chiral phosphoric acid catalyzed aza-Friedel-Crafts alkylation of indoles with cyclic aryl α-ketimino esters

A highly enantioselective aza-Friedel-Crafts alkylation of indoles with cyclic aryl α-ketimino esters catalyzed by a chiral phosphoric acid has been developed, the corresponding α,α-disubstituted unnatural α-amino ester derivatives were obtained in moderate to high yields (67–85%) with high enantioselectivities (up to 93% ee) under mild reaction conditions.

ChemInform Abstract: Dual Photoredox/Gold Catalysis Arylative Cyclization of o‐Alkynylphenols with Aryldiazonium Salts: A Flexible Synthesis of Benzofurans.

A new method for the arylative cyclization of o-alkynylphenols with aryldiazonium salts via dual photoredox/gold catalysis is described. The reaction proceeds smoothly at room temperature in the absence of base and/or additives and offers an efficient approach to benzofuran derivatives. The scope of the transformation is wide, and the limitations are discussed. The reaction is proposed to proceed through a photoredox-promoted generation of a vinylgold(III) intermediate that undergoes reductive elimination to provide the heterocyclic coupling adduct.