Reaction Of Alkyl Halides Research Articles

Copper(I) Iodide-Catalyzed Perfluoroalkoxylation Reaction of Alkyl Halides.

We report an efficient perfluoroalkoxylation reaction of alkyl halides catalyzed by copper(I) iodide (CuI), which facilitates the simultaneous activation of both perfluoroalkoxide and alkyl halides. This methodology is tolerant of a wide range of functional groups and eliminates the need for costly metal reagents. The reaction is conducted in a single step under mildly practical conditions.

Oxidative Substitution of Organocopper(II) by a Carbon-Centered Radical.

Copper-catalyzed coupling reactions of alkyl halides are believed to prominently involve copper(II) species and alkyl radicals as pivotal intermediates, with their exact interaction mechanism being the subject of considerable debate. In this study, a visible light-responsive fluoroalkylcopper(III) complex, [(terpy)Cu(CF3)2(CH2CO2tBu)] Trans-1, was designed to explore the mechanism. Upon exposure to blue LED irradiation, Trans-1 undergoes copper-carbon bond homolysis, generating Cu(II) species and carbon-centered radicals, where the carbon-centered radical then recombines with the Cu(II) intermediate, resulting in the formation of Cis-1, the Cis isomer of Trans-1. Beyond this, a well-defined fluoroalkylcopper(II) intermediate ligated with a sterically hindered ligand was isolated and underwent full characterization and electronic structure studies. The collective experimental, computational, and spectroscopic findings in this work strongly suggest that organocopper(II) engages with carbon-centered radicals via an "oxidative substitution" mechanism, which is likely the operational pathway for copper-catalyzed C-H bond trifluoromethylation reactions.

Photoinduced Pd-Catalyzed Intramolecular 6-endo Heck Reaction of Alkyl Halides.

A novel photocatalytic palladium-induced 6-endo-selective alkyl Heck reaction of unactivated alkyl iodides and alkyl bromides has been described. This strategy facilitates the gentle and efficient synthesis of a variety of 5-phenyl-1,2,3,6-tetrahydropyridine derivatives. It demonstrates a broad substrate tolerance and excellent 6-endo selectivity. Unlike the high-temperature requirements of traditional alkyl Heck reactions, this transformation efficiently proceeds at room temperature and shows significant promise for industrial-scale applications. Mechanistic investigations reveal that this alkyl Heck reaction proceeds via a hybrid palladium-radical process.

Cross‐Coupling Reaction of Alkyl Halides with Aldehydes through NHC Catalysis

AbstractDuring the past decades, N‐heterocyclic carbene (NHC)‐catalyzed reactions have emerged as a versatile tool in synthetic chemistry. In particular, NHC‐catalyzed cross‐coupling reaction has been significantly developed in many respects, including new reaction development and mechanistic investigation. This concept article presents recent advances towards direct cross‐coupling reactions of aldehydes with alkyl halides enabled by NHC organocatalysis.

Alcohol synthesis based on the SN2 reactions of alkyl halides with the squarate dianion.

A convenient method has been developed for transforming alkyl halides into the corresponding alcohols via an SN2 reaction. Treatment of an alkyl halide with the squarate dianion at high temperature produces mono-alkyl squarate, and a one-pot basic hydrolysis of the intermediate affords the alcohol in good yield.

Oxidative Addition and β-Hydride Elimination by a Macrocyclic Dinickel Complex: Observing Bimetallic Elementary Reactions.

The dinickel(I) complex Ni2 (tBu PONNOPONNO), featuring a planar macrocyclic diphosphoranide ligand tBu PONNOPONNO, offers a unique architectural platform for observing bimetallic elementary reactions. Oxidative addition reactions of alkyl halides produce dinickel(II) complexes of the type Ni2 (μ-R)(μ-X)(tBu PONNOPONNO). However, when R=Et β-hydride elimination is observed to form a dinickel monohydride, with the rate dependent on the nature of X. DFT studies suggest a new mechanism for bimetallic β-hydride elimination, where the rate dependence arises from the steric pressure imposed by the X group on the opposing trans face of the dinickel macrocycle. This work enhances understanding of bimetallic elementary reactions, particularly β-hydride elimination, which have not been well-explored for dinuclear systems.

Exploring The Synthesis of 1,2,4-Triazole Derivatives: A Comprehensive Review

The pharmacological activities of triazole derivatives have been studied extensively by researchers. Different derivatives of triazole have showed promise in treating various diseases. Most triazole derivatives have demonstrated anti-inflammatory, anti-cancer, anti-bacterial and anti-fungal activities. The ability of these compounds to modulate various biological processes has made them attractive for pharmaceutical development. Furthermore, the low cost and wide availability of triazoles have made them even more attractive for drug development. In addition to the pharmacological activities, triazole derivatives have also been reported to possess antioxidant properties. Studies have shown that 1,2,3-triazole can protect against oxidative damage and inhibit lipid peroxidation. Furthermore, 1,2,4-triazole has been found to act as an antioxidant and scavenge free radicals. The antioxidant properties of triazoles make them attractive for the development of new drugs. The synthesis of triazole derivatives has also been studied extensively. Various methods have been developed to synthesize triazole derivatives, including chemical and enzymatic methods. Chemical methods involve the formation of cyclic structures by the reaction of alkyl halides with azides. Enzymatic methods involve the use.

Perfluoroalkoxylation reaction via dual concurrent catalysis.

A catalytic amount of CsI enables dual concurrent activation of poorly reactive perfluoroalkoxide and alkyl halides, especially alkyl chlorides, leading to the formation of diverse perfluoroalkoxylated organic compounds. Installation of perfluoroalkoxy groups by this methodology is cost-effective, circumventing the need for over-stoichiometric cesium or silver salts. This methodology also provides high functional group compatibility and tolerance of sterically hindered substrates.

Zeolites catalyze the halogen exchange reaction of alkyl halides

Simple zeolites (NaY, NaX,…) catalyze the halogen switch between two different alkyl halides under either batch or flow reaction conditions. Sodalite cages are proposed to trigger the transformation.

Photoredox Activation of Organozinc Reagents: Barbier-Type Reaction of Alkyl Halides with α-(Trifluoromethyl)styrenes.

Organozinc reagents may be activated under blue light irradiation using an organic photocatalyst to generate alkyl radicals. The radicals are trapped by α-(trifluoromethyl)styrenes leading to gem-difluorinated products after elimination of fluoride. The reaction can be conveniently performed under Barbier conditions starting from organic iodides and bromides and elemental zinc.

Air-Stable Iron-Based Precatalysts for Suzuki-Miyaura Cross-Coupling Reactions between Alkyl Halides and Aryl Boronic Esters.

The development of an air-stable iron(III)-based precatalyst for the Suzuki-Miyaura cross-coupling reaction of alkyl halides and unactivated aryl boronic esters is reported. Despite benefits to cost and toxicity, the proclivity of iron(II)-based complexes to undergo deactivation via oxidation or hydrolysis is a limiting factor for their widespread use in cross-coupling reactions compared to palladium-based or nickel-based complexes. The new octahedral iron(III) complex demonstrates long-term stability on the benchtop as assessed by a combination of 1H NMR spectroscopy, Mössbauer spectroscopy, and its sustained catalytic activity after exposure to air. The improved stability of the iron-based catalyst facilitates an improved protocol in which Suzuki-Miyaura cross-coupling reactions of valuable substrates can be assembled without the use of a glovebox and access a diverse scope of products similar to reactions assembled in the glovebox with iron(II)-based catalysts.

The Effect of Added Ligands on the Reactions of [Ni(COD)(dppf)] with Alkyl Halides: Halide Abstraction May Be Reversible.

The reactions of dppf-nickel(0) with alkyl halides proceed via three-coordinate nickel(0) intermediates of the form [Ni(dppf)(L)]. The effects of the identity of the added ligand (L) on catalyst speciation and the rates of reactions of [Ni(COD)(dppf)] with alkyl halides have been investigated using kinetic experiments and density functional theory calculations. A series of monodentate ligands have been investigated in attempts to identify trends in reactivity. Sterically bulky and electron-donating ligands are found to decrease the reaction rate. It was found that (i) the halide abstraction step is not always irreversible and the subsequent recombination of a nickel(I) complex with an alkyl halide can have a significant effect on the overall rate of the reaction and (ii) some ligands lead to very stable [Ni(dppf)(L)2] species. The yields of prototypical (dppf)nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are significantly improved by the addition of free ligands, which provides another important variable to consider when optimizing nickel-catalyzed reactions of alkyl halides.

Copper-Catalyzed Carbonylative Coupling of Alkyl Halides.

Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to introduce oxygen functionality into organic compounds, with CO acting as an inexpensive and readily available C1 feedstock. Despite the long history of carbonylation catalysis, including many processes that have been industrialized at bulk scale, there remain several challenges to tackle. For example, noble metals such as Pd, Rh, and Ir are typically used as catalysts for carbonylation reactions, rather than earth-abundant alternatives. Additionally, while carbonylation of C(sp2)-hybridized substrates (e.g., aryl halides) is well-known, carbonylation of unactivated alkyl electrophiles, especially where β-hydride elimination can compete with desired CO migratory insertion at the catalyst site, remains challenging for many systems. Recently, base metal catalysis based on Mn, Co, and other metals has enabled advances in carbonylative coupling of alkyl electrophiles, though the nucleophiles are often limited to alcohols or amines to generate esters or amides as products. Thus, we have targeted base metal-catalyzed carbonylative C-C and C-E (E = N, H, Si, B) coupling reactions as a method for approaching diverse carbonyl compounds of synthetic importance.Initially, we designed a heterobimetallic catalyst platform for carbonylative C-C coupling of alkyl halides with arylboronic esters (i.e., carbonylative Suzuki-Miyaura coupling) to generate aryl alkyl ketones. Subsequently, we developed multicomponent carbonylation reactions of alkyl halides using NHC-Cu catalysts (NHC = N-heterocyclic carbene). These reactions operate by radical mechanisms, converting alkyl halides into either acyl radical or acyl halide intermediates that undergo subsequent C-C or C-E coupling at the Cu site. This mechanistic paradigm is relatively novel in the metal-catalyzed carbonylation area, allowing us to discover a previously unexplored chemical space in carbonylative coupling catalysis. We have successfully developed the following reactions: (a) hydrocarbonylative coupling of alkynes with alkyl halides; (b) borocarbonylative coupling of alkynes with alkyl halides; (c) reductive aminocarbonylation of alkyl halides with nitroarenes; (d) reductive carbonylation of alkyl halides; (e) carbonylative silylation of alkyl halides; (f) carbonylative borylation of alkyl halides. These reactions provide a broad range of valuable products including ketones, allylic alcohols, β-borylenones, amides, alcohols, acylsilanes, and acylborons in an efficient manner. Notably, the preparation of some of these products has previously required multistep syntheses, harsh conditions, or specialized reagents. By contrast, the multicomponent coupling platform that we have developed requires only readily available building blocks and rapidly increases molecular complexity in a single synthetic manipulation.

Representations in Organic Chemistry Textbooks: Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

Alkil halojenürlerin nükleofilik yer değiştirme ve ayrılma tepkimeleri, organik kimya dersi içerisinde pek çok kez karşılaşılan temel tepkimelerin başında gelmektedir. Bu açıdan ders kitaplarında organik kimya dersi açısından son derece önemli yere sahip olan bu tepkimelerde farklı gösterimlere yer verilmesi ve bunların birbiriyle bütünleştirilmesi önem taşımaktadır. Bu nedenle, bu araştırmada Türkiye’deki Kimya Eğitimi Anabilim Dallarında organik kimya derslerinde sıklıkla yararlanılan ders kitaplarında alkil halojenürlerin nükleofilik yer değiştirme ve ayrılma tepkimelerine ilişkin ne tür gösterimlerin kullanıldığının ortaya konulması amaçlanmıştır. Bu amaçla, dört ders kitabında bu tepkimelerin sözel, sembolik ve görsel gösterim türlerine göre nasıl temsil edildiği betimsel olarak incelenmiştir. Analiz sonuçları, hem yer değiştirme hem de ayrılma tepkimelerinde en çok sözel gösterimlere yer verildiğini, bunun ardından sembolik gösterimin geldiğini ortaya koymuştur. Ayrıca araştırmada stereokimya gibi oldukça soyut olan konu içeriğinde dahi görsel gösterimlere tüm ders kitaplarında son derece az yer verildiği belirlenmiştir. Son olarak araştırma, ayırma reaksiyonlarında nükleofilik yer değiştirme reaksiyonlarından daha az görsel temsil olduğunu ortaya koymuştur.

Unexpected Nickel Complex Speciation Unlocks Alternative Pathways for the Reactions of Alkyl Halides with dppf-Nickel(0).

The mechanism of the reactions between dppf-Ni0 complexes and alkyl halides has been investigated using kinetic and mechanistic experiments and DFT calculations. The active species is [Ni(κ2-dppf)(κ1-dppf)], which undergoes a halide abstraction reaction with alkyl halides and rapidly captures the alkyl radical that is formed. The rates of the reactions of [Ni(COD)(dppf)] with alkyl halides and the yields of prototypical nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are shown to be significantly improved by the addition of free dppf ligand.

Nickel-Catalyzed Multicomponent Coupling Reaction of Alkyl Halides, Isocyanides and H2O: An Expedient Way to Access Alkyl Amides

We herein describe a Ni-catalyzed multicomponent coupling reaction of alkyl halides, isocyanides, and H2O to access alkyl amides. Bench-stable NiCl2(dppp) is competent to initiate this transformation under mild reaction conditions, thus allowing easy operation and adding practical value. Substrate scope studies revealed a broad functional group tolerance and generality of primary and secondary alkyl halides in this protocol. A plausible catalytic cycle via a SET process is proposed based on preliminary experiments and previous literature.

Two Routes for the Synthesis of Phosphorothioates via P‐S Coupling Reaction of Dialkyl Phosphites with Thiols or a Mixture of Alkyl Halides and Thiourea in the Presence of CaO

AbstractIn this report, two routes for the synthesis of phosphorothioates via a P−S cross coupling reaction of thiols with dialkyl phosphites or a three component reaction of alkyl halides, thiourea and dialkyl phosphite in the presence of CaO has been studied. By presented methods, various phosphorothioates are obtained under transition metal‐free condition. The reactions are proceeded with formation of a known intermediate of disulfide via the oxidation of thiols and followed by nucleophilic substitution of dialkyl phosphite with the disulfide intermediate gave phosphorothioate.

A Copper‐Catalyzed Sonogashira Coupling Reaction of Diverse Activated Alkyl Halides with Terminal Alkynes Under Ambient Conditions

AbstractWe describe a copper‐catalyzed Sonogashira coupling reaction of alkyl halides with terminal alkynes under ambient conditions, efficiently providing a versatile tool for the construction of substituted alkynes. A new proline‐based N,N,P‐ligand is utilized to promote the transformation under a mild reaction condition. Diverse alkyl halides, such as primary and secondary (hetero)benzyl chlorides and bromides, secondary and tertiary α‐bromo amides and propargylic bromide, are applicable to provide a wide array of alkynes.magnified image

One-pot efficient synthesis of β-aryl-β-sulfanyl ketones via a four-component reaction of alkyl halides, thiourea benzaldehydes and acetophenones

A one-pot efficient synthesis of β-aryl-β-sulfanyl ketones is introduced via a tandem aldol condensation-thia-Michael addition process using NaOH in the poly ethylene glycol (PEG-200). Addition of different thiols in situ generated from the reaction of alkyl halides with thiourea to chalcones, formed in situ from the condensation of acetophenone derivatives with benzaldehydes, led to a high yielding synthesis of the products.

Cross‐Coupling Reactions of Alkyl Halides with Aryl Grignard Reagents Using a Tetrachloroferrate with an Innocent Countercation

AbstractBis(triphenylphosphoranylidene)ammonium tetrachloroferrate, (PPN)[FeCl4] (1), was evaluated as a catalyst for cross‐coupling reactions. 1 exhibits high stability toward air and moisture and is an effective catalyst for the reaction of secondary alkyl halides with aryl Grignard reagents. The PPN cation is considered as an innocent counterpart to the iron center. We have developed an easy‐to‐handle iron catalyst for “ligand‐free” cross‐coupling reactions.magnified image