[8+3]‐Cycloaddition of Tropones with Azaoxyallyl Cations

Although azaoxyallyl cations are widely used as 1,3‐dipoles for various cycloaddition reactions leading to nitrogen‐containing heterocycles, their application in higher‐order cycloaddition reaction remains scarce. Herein, we present the [8+3]‐cycloaddition reaction of tropones with in situ generated azaoxyallyl cations allowing the one‐step construction of cycloheptatriene‐fused 1,4‐oxazinones in moderate to good yields. This base‐promoted new carbon‐oxygen and carbon‐nitrogen bond‐forming reaction takes place under mild conditions in the absence of transition metal catalysts.     

Carbophilic 3‐Component Cascades: Access to Complex Bioactive Cyclopropyl Diindolylmethanes

Naturally occurring indole‐3‐carbinol and 3,3‐diindolylmethane show bioactivity in a number of disparate disease areas, including cancer, prompting substantial synthetic analogue activity. We describe a new approach to highly functionalised derivatives that starts from allene gas and proceeds via the combination of a three‐component Pd⁰‐catalysed cascade with a one‐pot, three‐component carbophilic Pt^II cascade linked to a stereoselective acid‐catalysed Mannich–Michael reaction that generates complex cyclopropyl diindolylmethanes which show selective activity against prostate cancer cell lines.     

Electrophilic Activation of Iodonium Ylides by Halogen‐Bond‐Donor Catalysis for Cross‐Enolate Coupling

The umpolung alkylation of silyl enol ethers with an iodonium(III) ylide proceeds under mild conditions to afford various 1,4‐dicarbonyl compounds in high yields in the presence of a halogen‐bonding catalyst. Unlike typical transition‐metal activation processes of such ylide precursors, which tend to proceed via carbenoid intermediates, experimental and computational studies indicate that halogen bonding (XB) between the XB donor catalyst and the iodonium ylide plays a crucial role in promoting the reaction. The identification of a compatible Bronsted base catalyst enabled the extension of this method to enols generated in situ to give the corresponding adducts in good yields.     

Synthesis of Methylene‐Bridged Biscarbazole Alkaloids by using an Ullmann‐type Coupling: First Total Synthesis of Murrastifoline‐C and Murrafoline‐E

We describe the total synthesis of methylene‐bridged biscarbazole alkaloids by using a late‐stage Ullmann‐type coupling of fully functionalised carbazole subunits. The carbazole derivatives were synthesised via a sequence of palladium(0)‐ and palladium(II)‐catalysed coupling reactions. Our approach has provided bismurrayafoline‐A, bismurrayafolinol, chrestifolines B–D, and the first total synthesis of murrastifoline‐C and murrafoline‐E.     

Palladium‐Catalyzed Stereoselective Intramolecular Oxidative Amidation of Alkenes in the Synthesis of 1,3‐ and 1,4‐Amino Alcohols and 1,3‐Diamines

An efficient and practical Pd‐catalyzed intramolecular oxidative allylic amidation provides facile access to derivatives of 1,3‐ and 1,4‐amino alcohols and 1,3‐diamines. The method operates under mild reaction conditions (RT) with molecular oxygen (1 atm) as the sole reoxidant of Pd. Excellent diastereoselectivities were attained with substrates bearing a secondary stereogenic center     

Base‐Promoted α‐Alkylation of Arylacetonitriles with Alcohols

A practical method to synthesize α‐alkylated arylacetonitriles from arylacetonitriles and alcohols without using any expensive transition metal complexes is demonstrated here. Following this base‐catalysed sustainable procedure, various arylacetonitriles were successfully alkylated with different alcohols. The practical applicability of this protocol was extended by one‐pot synthesis of important carboxylic acid derivatives.     

Late‐Stage Diversification of Peptides by Metal‐Free CH Arylation

The bioorthogonal late‐stage diversification of functionalized oligopeptides was accomplished through a metal‐free, site‐selective C?H arylation of engineered indole derivatives under mild reaction conditions.     

Synthesis of Quinolines via a Metal‐Catalyzed Dehydrogenative N‐Heterocyclization

Efficient ruthenium‐, rhodium‐, palladium‐, copper‐ and iridium‐catalysed methodologies have been recently developed for the synthesis of quinolines by the reaction of 2‐aminobenzyl alcohols with carbonyl compounds (aldehydes and ketones) or the related alcohols. The reaction is assumed to proceed via a sequence involving initial metal‐catalysed oxidation of 2‐aminobenzyl alcohols to the related 2‐aminobenzaldehydes, followed by cross aldol reaction with a carbonyl compound under basic conditions to afford α,β‐unsaturated carbonyl compounds. These aldehydes or ketones can be also generated in situ via dehydrogenation of the related primary and secondary alcohols. In the final step cyclodehydration of the α,β‐unsaturated carbonyl compound intermediates gives quinolines. Good yields of quinolines were also obtained by reacting 2‐nitrobenzyl alcohols and secondary alcohols in the presence of a ruthenium catalyst. Finally, aniline derivatives afforded also a useful access to quinolines by the reaction with 1,3‐propanediol or 3‐amino‐1‐propanol, or in a three‐component reaction with benzyl alcohol and aliphatic alcohols.     

Formamide Synthesis through Borinic Acid Catalysed Transamidation under Mild Conditions

A highly efficient and mild transamidation of amides with amines co‐catalysed by borinic acid and acetic acid has been reported. A wide range of functionalised formamides was synthesized in excellent yields, including important chiral α‐amino acid derivatives, with minor racemisation being observed. Experiments suggested that the reaction rely on a cooperative catalysis involving an enhanced boron‐derived Lewis acidity rather than an improved Brønsted acidity of acetic acid.     

Transition‐Metal‐Free Synthesis of N‐Hydroxy Oxindoles by an Aza‐Nazarov‐Type Reaction Involving Azaoxyallyl Cations

A novel transition‐metal‐free method to construct N‐hydroxy oxindoles by an aza‐Nazarov‐type reaction involving azaoxyallyl cation intermediates is described. A variety of functional groups were tolerated under the weak basic reaction conditions and at room temperature. A one‐pot process was also developed to make the reaction even more practical. This method provides alternative access to oxindoles and their biologically active derivatives.     

Ring Opening of 2‐(Benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones and 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones

Substituted 2‐(benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones are unstable under alkaline and acidic conditions, undergoing opening of the benzoxazinone ring. 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones show similar degradation under alkaline conditions, while replacement of Br at C(2) to give 2‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐ones was observed only under mild alkaline conditions. Mechanisms of ring opening and degradation to 2‐aminophenol derivatives are proposed.     

Design and characterization of Dendrimer of MNPs as a novel,heterogeneous and reusable nanomagnetic organometallic catalyst for one‐pot synthesis of hydroxyl naphthalene‐1,4‐dione derivatives under solvent‐free conditions

A novel super acidic magnetic nanoparticle as catalyst was successfully synthesized. The preparation of this dendrimer sulfonic acid functionalized γ‐Fe₂O₃ magnetic core‐shell silica nanoparticles as a new recoverable and heterogeneous nanocatalyst was described. The new catalyst was characterized using various techniques such as scanning electron microscopy (SEM), energy dispersive spectrum (EDS), and thermo gravimetric synthesis (TGA). Moreover, we have examined the catalytic activity of the catalyst for one‐pot, efficient and facile synthesis of 2‐hydroxy‐1,4‐naphthoquinone derivatives via a three‐component condensation reaction of 2‐hydroxynaphthalene‐1,4‐dione, aromatic aldehydes and aniline derivatives. High yields of products, short reaction times, waste‐free, mild, ambient and solvent‐free reaction conditions are advantages of this protocol. Also, the catalyst can be easily recovered by an external magnetic and reused several times without significant loss of its catalytic activity.     

Organocatalytic Green Approach Towards the Fabrication of Fused Benzo N,N‐containing Heterocycles Facilitated by Ultrasonic Irradiation

The development of a metal‐free protocol for transformations in organic synthesis offers a significant potential environmental benefit. This article reports the exploration of meglumine, a nontoxic and biodegradable amino sugar, as an organocatalyst for the synthesis of biologically active 1H‐dibenzo[b,e][1,4]diazepin‐1‐ones, highly regioselective benzimidazole derivatives and derivatives of quinoxalines. Operational simplicity, mild reaction conditions, shorter reaction times, and use of green solvents are the highlights of this protocol. The advantage of ultrasonic irradiation has been significantly explored for the synthesis of the aforesaid compounds. Furthermore, the multifaceted use of o‐phenylenediamine has also been accentuated in the study.     

Metal‐Free Annulation of Arenes with 2‐Aminopyridine Derivatives: The Methyl Group as a Traceless Non‐Chelating Directing Group

A novel annulation reaction between 2‐aminopyridine derivatives and arenes under metal‐free conditions is described. The presented intermolecular transformation provided straightforward access to the important pyrido[1,2‐a]benzimidazole scaffold under mild reaction conditions. The unprecedented application of the methyl group of methylbenzenes as a traceless, non‐chelating, and highly regioselective directing group is reported.     

One‐Pot Synthesis of 1,4‐Oxathiino[2,3‐b]quinoxalines or ‐pyrazines from 2,3‐Dichloroquinoxaline or ‐pyrazine and 1‐Aryl‐2‐bromoalkan‐1‐ones

An efficient one‐pot synthesis of novel heterocyclic derivatives, 2‐aryl‐1,4‐oxathiino[2,3‐b]quinoxalines or ‐pyrazines 5 , via the reaction of 2,3‐dichloroquinoxaline or ‐pyrazine with Na₂S?9 H₂O, and subsequent treatment of the resulting 2‐chloro‐3‐sodiosulfanylquinoxaline or ‐pyrazine 2 with 1‐aryl‐2‐bromo‐1‐alkanones and then NaH under mild conditions is described.     

Transition‐Metal‐Free Formal Decarboxylative Coupling of α‐Oxocarboxylates with α‐Bromoketones under Neutral Conditions: A Simple Access to 1,3‐Diketones

A transition‐metal‐free formal decarboxylative coupling reaction between α‐oxocarboxylates and α‐bromoketones to synthesize 1,3‐diketone derivatives is presented. In this reaction, a broad scope of substrates can be employed, and neither a metal‐based reagent nor an additional base is required. DFT calculations reveal that this reaction proceeds through a coupling followed by decarboxylation mechanism and the α‐bromoketone unprecedentedly serves as a nucleophile under neutral conditions. The rate‐determining step is an unusual hydrogen‐bond‐assisted enolate formation by thermolysis.     

A Scalable Metal‐, Azide‐, and Halogen‐Free Method for the Preparation of Triazoles

A scalable metal‐, azide‐, and halogen‐free method for the synthesis of substituted 1,2,3‐triazoles has been developed. The reaction proceeds through a 3‐component coupling of α‐ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional‐group tolerance with respect to both the α‐ketoacetal and amine coupling partners, providing access to 4‐, 1,4‐, 1,5‐, and 1,4,5‐substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3‐triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.     

A Metal‐Free Synthesis of 2‐Alkyl(or Aryl) Thiomethyl‐2‐cyclohexenones from Cyclic Morita–Baylis–Hillman Bromides

Under mild conditions, an efficient and rapid S‐allylation of thiols with cyclic Morita–Baylis–Hillman (MBH) bromides without the need of a transition‐metal catalyst or an expensive additive is described herein. Treatment of the MBH bromides with various thiols or ethane‐1,2‐dithiol in the presence of Et₃N regioselectively affords the corresponding 2‐alkyl(or aryl) thiomethyl‐2‐cyclohexenones or the perhydro benzo[1,4]dithiepinone, respectively, in moderate to good yields (40 – 73%). The reaction is rapid and carried out in THF at room temperature.     

[Emim][BF4]: An Efficient Green Protocol for the Synthesis of Bioactive 2‐(5‐(substituted)‐2,6‐dioxo‐1,2,5,6‐tetrahydropyrimidin‐4‐yl)‐2,3‐dihydrophthalazine‐1,4‐dione Derivatives

The present study is designed to synthesize the 2‐(5‐(substituted)‐2,6‐dioxo‐1,2,5,6‐tetrahydropyrimidin‐4‐yl)‐2,3‐dihydrophthalazine‐1,4‐diones and investigate their anticancer activity. This is the first example of the condensation reaction of a series of phthalhydrazide derivatives in ionic liquid. In this investigation, the titled compounds syntheses were carried out by simple and efficient three component coupling of phthalhydrazide, aldehydes, and barbituric acid in the presence of [Emim][BF₄] ionic liquid. This methodology was provided and promotes the higher product yields in shorter reaction times and mild reaction conditions. The title compounds were tested for their anticancer activity. Some of them were shown the significant cytotoxic activity against the selected cancer cell lines.     

Hydrogenation of CO2‐Derived Carbonates and Polycarbonates to Methanol and Diols by Metal–Ligand Cooperative Manganese Catalysis

The first base‐metal‐catalysed hydrogenation of CO₂‐derived carbonates to alcohols is presented. The reaction proceeds under mild conditions in the presence of a well‐defined manganese complex with a loading as low as 0.25 mol %. The non‐precious‐metal homogenous catalytic system provides an indirect route for the conversion of CO₂ into methanol with the co‐production of value‐added (vicinal) diols in yields of up to 99 %. Experimental and computational studies indicate a metal–ligand cooperative catalysis mechanism.