Reagents In Organic Synthesis Research Articles

N‐Arylcyanothioformamides: Preparation Methods and Application in the Synthesis of Bioactive Molecules

AbstractThis comprehensive review discusses the various preparation methods of N‐arylcyanothioformamides and highlights the diverse chemistry and application of such reagents in organic synthesis since they were first reported. Specifically, the review describes applications of the preceding reagents in the preparation of the highly bioactive heterocyclic imidazolidineiminothiones, bis‐imidazolidineiminothiones and derivatives thereof. The review also demonstrates how N‐arylcyanothioformamides provide access to the highly coveted luciferin analogues for bioluminescence imaging applications. As well, the review showcases the metal complexation chemistry of N‐arylcyanothioformamides and the regiochemical outcome of its reactions with isocyanates versus isothiocyanates. Many examples are provided from the literature to show the scope and selectivity (regio, stereo, and chemo) in these transformations.

A Nanovessel-Catalyzed Three-Component Aza-Darzens Reaction.

It has been previously demonstrated that nanovessels can be highly competent catalysts providing high rate accelerations and unique selectivity to the organic transformations which they mediate. However, for supramolecular assemblies to be considered a standard reagent in organic synthesis they must first demonstrate the ability to catalyze increasingly complex transformations. Herein, we report a three-component Aza-Darzens reaction that generates N-phenylaziridines, catalyzed by a supramolecular host, that provides the stereoisomer opposite to the one generated in bulk solution (trans vs cis). This transformation constitutes a rare catalytic three-component coupling within a supramolecular assembly, providing a supramolecular solution to a synthetically challenging transformation.

Gold and hypervalent iodine(iii): liaisons over a decade for electrophilic functional group transfer reactions.

Over the last two decades, hypervalent iodine(iii) reagents have evolved from being 'bonding curiosities' to mainstream reagents in organic synthesis, in particular, electrophilic functional group transfer reactions. In this context, gold catalysts have not only emerged as a unique toolbox to facilitate such reactions (especially alkynylations) but also opened new possibilities with their different modes of reactivities for other functional group transfer reactions (acetoxylations and arylations). This feature article critically summarizes hitherto all such Au-catalyzed electrophilic functional group transfer reactions with hypervalent iodine(iii) reagents, emphasizing their mechanistic aspects.

Recent Advances in the Application of in-situ Generated Hypervalent Iodine Reagents in Organic Synthesis

Recent Advances in the Application of <i>in-situ</i> Generated Hypervalent Iodine Reagents in Organic Synthesis

One-pot Synthesis of Unsymmetrical Diaryliodonium Tetrafluoroborate Salts Bearing an Isoxazole Moiety from Aryl Boronic Acids

Hypervalent iodine compounds exhibit attractive features of low cost, mild and selective reagents in organic synthesis. These reagents serve as environmentally benign alternatives to toxic heavy-metal based oxidants and expensive organometallic catalysts. The practical and simple synthesis of unsymmetrical diaryl iodonium tetrafluoroborate salts is described. This synthetic method has allowed the production of isoxazole tetrafluoroborate salts from readily available aryl boronic acids without an extra anion exchange step in acceptable yields of 45% and 50%.

Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations.

Diazomethane is one of the most versatile reagents in organic synthesis, but its utility is limited by its hazardous nature. Although alternative methods exist to perform the unique chemistry of diazomethane, these suffer from diminished reactivity and/or correspondingly harsher conditions. Herein, we describe the repurposing of imidazotetrazines (such as temozolomide, TMZ, the standard of care for glioblastoma) for use as synthetic precursors of alkyl diazonium reagents. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, and results show that methyl ester formation from a wide variety of substrates is especially efficient and operationally simple. TMZ is a commercially available solid that is non-explosive and non-toxic, and should find broad utility as a replacement for diazomethane.

Cationic silicon Lewis acids in catalysis

Silylium ions, or, to be more precise, donor-stabilized silylium-ion-like species, were once only the domain of computational and structural chemists. This was mainly due to the difficulties in generating and isolating these reactive species in a condensed phase. Even chemists focused on reactivity stayed away from such delicate ions. The state of affairs has changed in recent years as methods for their preparation have become more accessible and strategies for their stabilization more effective. Silylium ions have high electrophilicity, oxophilicity and fluorophilicity that have seen them emerge as useful catalysts, including for unique transformations not accessible to metal catalysts. This Perspective aims to provide a concise and conceptual summary of breakthroughs in this emerging area. Silylium ions are highly reactive, strongly Lewis acidic and have historically been tricky to isolate. This Perspective highlights the range of methods available for their preparation and the latest examples of their use as catalysts or reagents in organic synthesis.

MALONYL PEROXIDES IN ORGANIC SYNTHESIS

A summary of the most recent applications of malonyl peroxides as reagents in organic synthesis is discussed. The microreview covers the latest selected examples on the usage of malonyl peroxides: dioxygenation and oxyamination of alkenes; oxidative C–O coupling with arenes, enol ethers, 1,3-dicarbonyl and N-heterocyclic compounds; sulfoxide synthesis.

Malonyl peroxides in organic synthesis (microreview)

A summary of the most recent applications of malonyl peroxides as reagents in organic synthesis is discussed. The microreview covers the latest selected examples on the usage of malonyl peroxides: dioxygenation and oxyamination of alkenes; oxidative C–O coupling with arenes, enol ethers, 1,3-dicarbonyl and N-heterocyclic compounds; sulfoxide synthesis.

From Dialkyltitanium Species to Titanacyclopropanes: An Ab Initio Study

Although the dialkoxytitanacyclopropanes are presented as important reagents in organic synthesis, the mechanism of their generation from dialkyltitanium species is not firmly established, as shown...

Recent Advances in Chalcones: Synthesis, Transformation and Pharmacological Activities

Chalcones are useful intermediates in the synthesis of heterocyclic compound and the unique reagents in organic synthesis. The usual approach to obtain chalcones is through Claisen-Schmidt condensation. Several novel heterocyclic chalcone analogs have emerged. Chalcones are multifunctional molecules that possess promising pharmacological activities. Chalcones are known for anti-cancer, antioxidant, anti-inflammatory, anti-microbial, anti-tubercular, antileishmanial, antimalarial, anthelmintic, osteogenic activities. This review article focuses on recent applications of Claisen-Schmidt condensation reaction employed in the synthesis of chalcone, its transformation to heterocyclic compounds and pharmacological activities.

Vinylidene Homologation of Boronic Esters and its Application to the Synthesis of the Proposed Structure of Machillene

Alkenyl boronic esters are important reagents in organic synthesis. Herein, we report that these valuable products can be accessed by the homologation of boronic esters with lithiated epoxysilanes. Aliphatic and electron-rich aromatic boronic esters provided vinylidene boronic esters in moderate to high yields, while electron-deficient aromatic and vinyl boronic esters were found to give the corresponding vinyl silane products. Through DFT calculations, this divergence in mechanistic pathway has been rationalized by considering the stabilization of negative charge in the C-Si and C-B bond breaking transition states. This vinylidene homologation was used in a short six-step stereoselective synthesis of the proposed structure of machillene, however, synthetic and reported data were found to be inconsistent.

Vinylidene Homologation of Boronic Esters and its Application to the Synthesis of the Proposed Structure of Machillene

AbstractAlkenyl boronic esters are important reagents in organic synthesis. Herein, we report that these valuable products can be accessed by the homologation of boronic esters with lithiated epoxysilanes. Aliphatic and electron‐rich aromatic boronic esters provided vinylidene boronic esters in moderate to high yields, while electron‐deficient aromatic and vinyl boronic esters were found to give the corresponding vinyl silane products. Through DFT calculations, this divergence in mechanistic pathway has been rationalized by considering the stabilization of negative charge in the C−Si and C−B bond breaking transition states. This vinylidene homologation was used in a short six‐step stereoselective synthesis of the proposed structure of machillene, however, synthetic and reported data were found to be inconsistent.

Efficient Cobalt Catalyst for Ambient-Temperature Nitrile Dihydroboration, the Elucidation of a Chelate-Assisted Borylation Mechanism, and a New Synthetic Route to Amides.

N,N-Diborylamines have emerged as promising reagents in organic synthesis; however, their efficient preparation and full synthetic utility have yet to be realized. To address both shortcomings, an effective catalyst for nitrile dihydroboration was sought. Heating CoCl2 in the presence of PyEtPDI afforded the six-coordinate Co(II) salt, [(PyEtPDI)CoCl][Cl]. Upon adding 2 equiv of NaEt3BH, hydride transfer to one chelate imine functionality was observed, resulting in the formation of (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co. Single-crystal X-ray diffraction and density functional theory calculations revealed that this compound possesses a low-spin Co(II) ground state featuring antiferromagnetic coupling to a singly reduced imino(pyridine) moiety. Importantly, (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co was found to catalyze the dihydroboration of nitriles using HBPin with turnover frequencies of up to 380 h-1 at ambient temperature. Stoichiometric addition experiments revealed that HBPin adds across the Co-Namide bond to generate a hydride intermediate that can react with additional HBPin or nitriles. Computational evaluation of the reaction coordinate revealed that the B-H addition and nitrile insertion steps occur on the antiferromagnetically coupled triplet spin manifold. Interestingly, formation of the borylimine intermediate was found to occur following BPin transfer from the borylated chelate arm to regenerate (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co. Borylimine reduction is in turn facile and follows the same ligand-assisted borylation pathway. The independent hydroboration of alkyl and aryl imines was also demonstrated at 25 °C. With a series of N,N-diborylamines in hand, their addition to carboxylic acids allowed for the direct synthesis of amides at 120 °C, without the need for an exogenous coupling reagent.

Neutral‐Eosin‐Y‐Photocatalyzed Silane Chlorination Using Dichloromethane

AbstractChlorosilanes are versatile reagents in organic synthesis and material science. A mild pathway is now reported for the quantitative conversion of hydrosilanes to silyl chlorides under visible‐light irradiation using neutral eosin Y as a hydrogen‐atom‐transfer photocatalyst and dichloromethane as a chlorinating agent. Stepwise chlorination of di‐ and trihydrosilanes was achieved in a highly selective fashion assisted by continuous‐flow micro‐tubing reactors. The ability to access silyl radicals using photocatalytic Si−H activation promoted by eosin Y offers new perspectives for the synthesis of valuable silicon reagents in a convenient and green manner.

Neutral-Eosin-Y-Photocatalyzed Silane Chlorination Using Dichloromethane.

Chlorosilanes are versatile reagents in organic synthesis and material science. A mild pathway is now reported for the quantitative conversion of hydrosilanes to silyl chlorides under visible-light irradiation using neutral eosin Y as a hydrogen-atom-transfer photocatalyst and dichloromethane as a chlorinating agent. Stepwise chlorination of di- and trihydrosilanes was achieved in a highly selective fashion assisted by continuous-flow micro-tubing reactors. The ability to access silyl radicals using photocatalytic Si-H activation promoted by eosin Y offers new perspectives for the synthesis of valuable silicon reagents in a convenient and green manner.

Nazarov Reagent: New Role for the [4+2] Domino Benzannulation Reaction to Construct Polysubstituted Benzenes.

A new role for the Nazarov reagent was revealed in the [4+2] benzannulation reaction, and delivered a series of polyfunctional benzenes in high yields under mild conditions. This metal-free process not only expanded the application of the Nazarov reagent in organic synthesis, but also provided a new, efficient way to construct polyfunctional benzenes.

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones.

Functionally substituted sulfones with stereogenic centers are valuable reagents in organic synthesis and key motifs in some bioactive compounds. The asymmetric Michael addition of β-ketosulfones to conjugated nitroalkenes in the presence of Ni(II) complexes with various chiral vicinal diamines was studied. This reaction provides convenient access to non-racemic 4-nitro-2-sulfonylbutan-1-ones with two stereocenters with high yield and excellent enantioselectivity (up to 99%). It has been established that the catalytic Michael reaction itself was carried out with high diastereoselectivity, but the Michael adducts may epimerize at the C-2 position at a significant rate. Conditions for the preparation of individual diastereomers were found.

2-Cyano-3-(dimethylamino)prop-2-ene Thioamide: A New Reagent for Synthesis of Functionalized 4-Unsubstituted Ethyl Nicotinates and Nicotinonitriles

Condensation of cyclopent(hex)ylidenecyanothioacetamide with N, N-dimethylformamide dimethyl acetal led to the formation of a new reagent for organic synthesis: 2-cyano-3-(dimethylamino)prop-2-ene thioamide. On its basis a series of ethyl nicotinates and nicotinonitriles were synthesized by a vinyl substitution reaction.

The Puzzling Monopentamethylcyclopentadienyltitanium(III) Dichloride Reagent: Structure and Properties.

Following the track of the useful titanocene [Ti(η5-C5H5)2Cl] reagent in organic synthesis, the related half-sandwich titanium(III) derivatives [Ti(η5-C5R5)Cl2] are receiving increasing attention in radical chemistry of many catalyzed transformations. However, the structure of the active titanium(III) species remains unknown in the literature. Herein, we describe the synthesis, crystal structure, and electronic structure of titanium(III) aggregates of composition [{Ti(η5-C5Me5)Cl2} n]. The thermolysis of [Ti(η5-C5Me5)Cl2Me] (1) in benzene or hexane at 180 °C results in the clean formation of [{Ti(η5-C5Me5)Cl(μ-Cl)}2] (2), methane, and ethene. The treatment of 1 with excess pinacolborane in hexane at 65 °C leads to a mixture of 2 and the paramagnetic trimer [{Ti(η5-C5Me5)(μ-Cl)2}3] (3). The X-ray crystal structures of compounds 2 and 3 show Ti-Ti distances of 3.267(1) and 3.219(12) Å, respectively. Computational studies (CASPT2//CASSCF and BS DFT methods) for dimer 2 reveal a singlet ground state and a relatively large singlet-triplet energy gap. Nuclear magnetic resonance spectroscopy of 2 in aromatic hydrocarbon solutions and DFT calculations for several [{Ti(η5-C5Me5)Cl2} n] aggregates are consistent with the existence of an equilibrium between the diamagnetic dimer [{Ti(η5-C5Me5)Cl(μ-Cl)}2] and a paramagnetic tetramer [{Ti(η5-C5Me5)(μ-Cl)2}4] in solution. In contrast, complex 2 readily dissolves in tetrahydrofuran to give a green-blue solution from which blue crystals of the mononuclear adduct [Ti(η5-C5Me5)Cl2(thf)] (4) were grown.