Catalytic Alkylation Research Articles

Iron-Catalyzed sp3 C-H Alkylation of Fluorene with Primary and Secondary Alcohols: A Borrowing Hydrogen Approach.

The utilization of earth-abundant, cheap, and nontoxic transition metals in important catalytic transformations is essential for sustainable development, and iron has gained significant attention as the most abundant transition metal. A mixture of FeCl2 (3 mol %), phenanthroline (6 mol %), and KOtBu (0.4 eqivalent) was used as an effective catalyst for the sp3 C-H alkylation of fluorene using alcohol as a nonhazardous alkylating partner, and eco-friendly water was formed as the only byproduct. The substrate scope includes a wide range of substituted fluorenes and substituted benzyl alcohols. The reaction is equally effective with challenging secondary alcohols and unactivated aliphatic alcohols. Selective mono-C9-alkylation of fluorenes with alcohols yielded the corresponding products in good isolated yields. Various postfunctionalizations of C-9 alkylated fluorene products were performed to establish the practical utility of this catalytic alkylation. Control experiments suggested a homogeneous reaction path involving borrowing hydrogen mechanism with the formation and subsequent reduction of 9-alkylidene fluorene intermediate.

Formation of C–C and C–N bonds through primary alcohol oxidation catalyzed by ruthenium(II) POCOP pincer complexes

In this study, we present the successful application of new and known stable 16‐electron ruthenium(II) pincer complexes POCOP, based on the naphthoresorcinate backbone, [Ru(X)(POCOP)(CO)] (X = H, Cl, Br, I, OCOCF3), in the catalytic alkylation of ketones and the coupling between amines and primary alcohols under mild conditions. These protocols demonstrated tolerance to a wide range of alcohols, ketones, and anilines, with reactions proceeding in high conversions and selectivity towards the hydrogenated ketones and the imines. The use of an excess of alcohol as the proton source facilitated the formation of the hydrogenated products. These results mark a significant advancement in the development of catalytic reactions with ruthenium POCOP pincer derivatives.

Efficiency of oxygenates on increase of octane number of reforming gasoline

At present, gasoline occupies one of the leading places among primary energy sources. The need of mankind in it, in its high quality, is greater than in any other fraction of hydrocarbons. Therefore, very high requirements are made to the operational properties of automobile gasoline, and the problem of improving the quality of gasoline is one of the urgent problems of the chemical industry. Modern vehicles require fuel with a high-octane number with properties preventing detonation and having octane numbers of 92, 95 and 98 for engines. High anti-detonation performance can be achieved through complex gasoline processing using catalytic cracking, isomerization and alkylation methods or by adding special high-octane additives to fuel. The world's leading trend in improving the environmental and performance characteristics of motor gasoline is the use of multifunctional additives, in particular oxygenates – compounds containing oxygen (such as alcohols, ketones, esters and others). The use of oxygen-containing components (oxygenates) is one of the promising ways to produce high-octane gasoline. Currently, in industrialized countries, oxygenates are actively used as a preferred substitute for organometallic anti-detonation additives and components of high-octane gasoline. In the presented work the properties of a new oxygenate - dimethyl ethynylcarbinol (DMEC), as an additive that increases the octane number of gasoline, are investigated. The study of the effect of oxygenates as methyl tert-butyl ether (MTBE) and DMEK on increasing the octane number of reforming gasoline showed that the increase in the octane number of gasoline when adding DMEK and binary additive is higher than when adding MTBE. According to the results of research, tertiary acetylene alcohol - DMEK can be offered as an oxygen-containing additive for automobile gasoline. The use of DMEK allows to expand the resources of high-octane components, reduce the toxicity of gasoline and exhaust gases, increase the production of high-quality commercial gasoline for automotive engines.

Plug Flow Reactor (PFR) Design for the Production of 100,000 tons per year of Cumene from the Catalytic Alkylation of Propylene and Benzene

In a bid to meet the ever-growing global demand for cumene based on its wide range of industrial applications and economic importance, the research considered the design of a plug-flow reactor (PFR) for the production of 100,000 tons of cumene per year from the catalytic alkylation of propylene and benzene. The PFR design models were developed by performing the mass and energy balance over the reactor at steady-state operation. The steady-state PFR performance models were simulated using the MATLAB R2023a version at an initial feed and operating temperature of 481.10 K and 483 K with varying fractional conversions from 0 to 0.95 at 0.05 intervals. At a maximum fractional conversion of 0.95, the PFR design specification for volume, height, diameter, space time, space velocity, quantity of heat generated, and quantity of heat generated per unit volume of the reactor was 19.7707 m3, 4.6523 m, 2.3261 m, 3.8766 s, 0.2580 s-1, 1.8035 J/s, and 0.03448 J/sm3, respectively. The profile behavior of the PFR functional parameters at changes in fractional conversion is in agreement with the trend for PFR operation at steady-state conditions, as shown in Figures 2–10. The evaluation of the PFR yearly production dependent on the reactor volume stood at $2,049.838. The article has shown that PFR is a suitable reaction medium for the catalytic alkylation process for optimum production of cumene and sustainability.

Perspectives for synthesis of linear alkylbenzenes via homogenous catalytic alkylation of benzene with olefin-containing complex mixtures: analysis of products composition using two-dimensional chromatography

Multicomponent mixtures with wide fraction of olefins obtained from thermal pyrolysis of higher paraffin’s were used for catalytic alkylation of benzene. Reaction was carried out in the presence of methanesulfonic acid as a homogenous catalyst, which has low corrosive properties compared to common industrial catalytic systems. The use of two-dimensional gas chromatography to analyze the composition of both the initial multicomponent raw material and the alkylation products allowed us to tune the initial conditions of the reaction and correctly calculate important parameters of the process such as selectivity and conversion. Thus, depending on the feedstock, the selectivity of LAB formation was varied in the range of 82.4–88.3 %, while for the 2-LAB it was varied between 29.2–41.3 % at ~90 % olefin conversion.

In-silico-assisted derivatization of triarylboranes for the catalytic reductive functionalization of aniline-derived amino acids and peptides with H2

Cheminformatics-based machine learning (ML) has been employed to determine optimal reaction conditions, including catalyst structures, in the field of synthetic chemistry. However, such ML-focused strategies have remained largely unexplored in the context of catalytic molecular transformations using Lewis-acidic main-group elements, probably due to the absence of a candidate library and effective guidelines (parameters) for the prediction of the activity of main-group elements. Here, the construction of a triarylborane library and its application to an ML-assisted approach for the catalytic reductive alkylation of aniline-derived amino acids and C-terminal-protected peptides with aldehydes and H2 is reported. A combined theoretical and experimental approach identified the optimal borane, i.e., B(2,3,5,6-Cl4-C6H)(2,6-F2-3,5-(CF3)2-C6H)2, which exhibits remarkable functional-group compatibility toward aniline derivatives in the presence of 4-methyltetrahydropyran. The present catalytic system generates H2O as the sole byproduct.

Mechanism and kinetics of catalytic decalin alkylation for the synthesis of high-performance fuel

Alkyl decalins are promising jet fuel components with high density and well cryogenic properties, but are difficult to obtain. Here we bring up a facile approach to synthesize methyl-substituted decalins including methyl decalin, dimethyl decalin and trimethyl decalin via catalytic alkylation reaction. The reaction conditions are optimized to obtain the high decalin conversion of 83.1 %. Based on a series of experiments, it is indicated that the intermediate complex formed by tetramethylsilane, aluminum chloride and dichloroethane is the key to accelerate the reaction rate, and the reaction mechanism is proposed. Moreover, a pseudo-first-order irreversible reaction dynamics is studied, and the reaction kinetics parameters and reaction rate equati andons are obtained. After vacuum distillation, the fuel product shows high density (0.872 g/cm3) and high volumetric neat heat of combustion (36.9 MJ/L), much higher than those of RP-3 fuel. This work provides a facile method to synthesize high-performance jet fuel.

The Catalytic Asymmetric Allylic Alkylation of Acyclic Enolates for the Construction of Quaternary and Tetrasubstituted Stereogenic Centres.

To facilitate the discovery and development of new pharmaceuticals, the demand for novel stereofunctionalised building blocks has never been greater. Whilst molecules bearing quaternary and tetrasubstituted stereogenic centres are ideally suited to explore untapped areas of chemical space, the asymmetric construction ofsterically congested carbon centres remains a longstanding challenge in organic synthesis. The enantioselective assembly of acyclic stereogenic centres is even more demanding due to the need to restrict a much wider range of geometries and conformations of the intermediates involved. In this context, the catalytic asymmetric allylicalkylation (AAA) of acyclic prochiral nucleophiles, namely enolates, has become an indispensable tool to access a range of linearα-quaternary andα-tetrasubstituted carbonyl compounds. However, unlike the AAA of cyclic enolates with a fixed enolate geometry, to achieve high levels of stereocontrol in the AAA of acyclic enolates, the stereoselectivity of enolisation must be considered. The aim of this review is to offer acomprehensivediscussion of catalytic AAA reactions of acyclic prochiral enolates and their analogues to generate congested quaternary and tetrasubstituted chiral centres using metal, non-metal and dual catalysis, with particular focus given to the control of enolate geometry and its impact on the stereochemical outcome of the reaction.

Iron- and base-catalyzed C(α)-alkylation and one-pot sequential alkylation-hydroxylation of oxindoles with secondary alcohols.

The utilization of economical and environmentally benign transition metals in crucial catalytic processes is pivotal for sustainable advancement in synthetic organic chemistry. Iron, as the most abundant transition metal in the Earth's crust, has gained significant attention for this purpose. A combination of FeCl2 (5 mol%) in the presence of phenanthroline (10 mol%) and NaOtBu (1.5 equivalent) proved effective for the C(α)-alkylation of oxindole, employing challenging secondary alcohol as a non-hazardous alkylating agent. The C(α)-alkylation of oxindole was optimized in green solvent or under neat conditions. The substrate scope encompasses a broad array of substituted oxindoles with various secondary alcohols. Further post-functionalization of the C(α)-alkylated oxindole products demonstrated the practical utility of this catalytic alkylation. One-pot C-H hydroxylation of alkylated oxindoles yielded 3-alkyl-3-hydroxy-2-oxindoles using air as the most sustainable oxidant. Low E-factors (3.61 to 4.19) and good Eco-scale scores (74 to 76) of these sustainable catalytic protocols for the alkylation and one-pot sequential alkylation-hydroxylation of oxindoles demonstrated minimum waste generation. Plausible catalytic paths are proposed on the basis of past reports and control experiments, which suggested that a borrowing hydrogen pathway is involved in this alkylation.

Catalytic stereodivergent allylic alkylation of 2-acylimidazoles for natural product synthesis

The stereocontrolled allylic alkylation of carbonyl compounds with the goal of producing the full range of stereoisomers presents an effective approach for increasing the productivity of collective natural product synthesis and the creation of chiral molecule libraries for drug exploration. The simultaneous control of regio-, diastereo-, and enantioselectivity poses a significant synthetic challenge in contemporary organic synthesis. Herein, we describe a catalytic stereodivergent α-allylation protocol applicable to both aliphatic and aromatic 2-acylimidazoles, thereby providing a practical blueprint for the divergent synthesis of important chiral building blocks. Each of the six isomeric α-allylated compounds can be readily obtained with remarkable yields and exceptional stereoselectivities, by judiciously selecting the appropriate leaving group and permutations of enantiomers adapted from nickel and iridium catalysts. The versatility of this asymmetric allylic alkylation has been successfully utilized in the enantioselective synthesis of (R)-arundic acid and (S,S)-cinamomumolide, as well as in the stereodivergent total synthesis of tapentadol.

Acidity Quantification and Structure Analysis of Amide-AlCl3 Liquid Coordination Complexes for C4 Alkylation Catalysis

Liquid coordination complexes (LCCs), which are formed between metal halides and donor molecules, represent promising catalysts. Six amide-AlCl3 LCCs were successfully synthesized, followed by their characterization through NMR, Raman, and UV-visible spectroscopy. The acidity of these LCCs was quantified by performing computational modelling of fluoride ion affinities (FIA) and experimental Gutmann–Beckett measurements. Spectroscopic analysis indicated bidentate coordination between amide ligands and Al, which induced asymmetric splitting of Al2Cl6 into diverse ions such as [AlCl2L2]+, [AlCl4]−, [AlCl3L], and [Al2Cl6L]. The computed FIA was found to align well with the experimental acidity trends, thereby confirming the proposed structure of the LCC. In the alkylation tests, the LCC with a high acidity demonstrated an increase in the yields of C5-C7 alkylates. These results provide an in-depth understanding of the tuneable structures of amide-AlCl3 LCCs. The acidity of LCCs can be controlled by tuning the ratio of the organic ligand to AlCl3, which allows bidentate coordination to facilitate asymmetric splitting of Al2Cl6. The LCCs demonstrate a high degree of potential as versatile and sustainable acid catalysts in alkylation reactions. These findings may advance the foundational knowledge of LCCs for the purpose of targeted acid catalyst design.

Enantioselective synthesis of fluorinated aromatic amino acids catalyzed by SPINOL-derived chiral quaternary ammonium salts†

We report the synthesis of a new class of chiral quaternary ammonium salts featuring a rigid spirobiindane scaffold. These chiral quaternary ammonium salts were employed as catalysts in the phase-transfer catalytic asymmetric alkylation of tert‑butyl glycinate–benzophenone Schiff base with both fluorinated and non-fluorinated benzyl bromides. Under the established reaction conditions, a series of chiral fluorinated aromatic α-amino acid derivatives, some of which are key intermediates for biologically significant compounds, were obtained in high yields and enantioselectivities.

Recent Developments on the Synthesis of Sulfoxides via Sulfenate Anions

AbstractSince the early 2000s, novel synthetic methods for the preparation of sulfoxides have emerged that involve sulfenate anions as sulfur nucleophiles. This short review showcases key advances in these sulfenate protocols, including catalytic enantioselective alkylation and arylation, and provides future directions for this research field.1 Introduction2 Precursors of Sulfenate Anions3 Organocatalytic Enantioselective Alkylation of Sulfenate Anions4 Palladium-Catalyzed Arylation of Sulfenate Anions5 Coupling of Sulfenate Anions with Hypervalent Iodine Reagents6 Conclusions and Outlook

Catalytic Enantioselective Alkylation of Aldehydes with 3-Bromooxindoles.

An asymmetric conjugate addition of aldehydes with o-azaxylylene intermediates (indol-2-ones) from 3-bromooxindoles has been developed. The use of a novel spiro-pyrrolidine (SPD)-derived bifunctional N-sulfonylated amide catalyst is essential for a highly diastereo- and enantioselective transformation to provide a wide array of enantioenriched C3 quaternary oxindoles with structurally diverse β-aldehyde appendages. Further application of this synthetic methodology enables the construction of the tricyclic cores of akuammiline-type alkaloids.

Iodine Molecules within Triethylenediamine-Based Metal-Organic Frameworks for Hydrolysis/Alkylation Tandem Reactions.

The integration of radionuclide iodine molecules in metal-organic frameworks (MOFs) for organic synthesis is attracting considerable research attention due to their specific catalytic performance. However, understanding the comprehensive catalytic behaviors of different types of molecular iodine encapsulated in MOFs for a sequential organic transformation is a great challenge. To address this issue, we have designed two triethylenediamine-functionalized MOFs assembled from 1,3,5-tricarboxyphenyl-2-(triethylenediaminemethyl)benzene-linker and {Cd(COO)3N} or {Cu4(u3-OH)2(COO)6N} clusters. Both MOFs show good stability and adsorption of I2 in the solution and vapor phases. Catalysts obtained after treatment with ethyl acetate present efficient catalytic activity in hydrolysis/alkylation tandem reactions in water. The mechanistic investigations disclose a sequential catalytic process comprising a "hidden" Brønsted acid catalytic hydrolysis of acetals to aldehydes followed by the I2-bonding Lewis acid catalytic alkylation of aldehydes to 3,3'-disubstituted 1H-indoles.

Impact of Catalyst Deuteration on the Reactivity of Chiral Phase-Transfer Organocatalysts.

Site-specifically deuterated organocatalysts were prepared and found to show improved reactivity over the non-deuterated analogs. Two privileged C2-symmetric chiral binaphthyl-modified tetraalkylammonium salts were selected for this study. The stability of these phase-transfer catalysts was generally improved by site-specific deuteration, though the degree of improvement was structure-dependent. In particular, a large secondary kinetic isotope effect was observed for the tetradeuterated phase-transfer catalyst. The performance of these deuterated catalysts in the asymmetric catalytic alkylation of amino acid derivatives was better than that of non-deuterated analogs at low catalyst loadings. The results suggest that catalyst-deuteration is a promising strategy for enhancing the stability and performance of organocatalysts.

Synthesis and Resolution of an Axially Chiral Spirocyclic Quaternary Ammonium Ion‐Based Phase‐Transfer Catalyst

AbstractWe report the synthesis of a novel spirocyclic quaternary ammonium salt that possesses axial chirality. Enantiopure material was obtained by fractional crystallization of the corresponding (R,R)‐tartrate salt. Application of this chiral quaternary ammonium salt in phase‐transfer catalytic asymmetric alkylation of glycinate Schiff base was examined.

Enantioselective Synthesis of Skipped Dienes via Iridium-Catalyzed Allylic Alkylation of Phosphonates.

An enantioselective synthesis of skipped dienes has been developed based on an iridium-catalyzed allylic alkylation of phosphonates and Horner-Wadsworth-Emmons olefination. This two-step protocol uses easily accessible substrates and delivers C2-substituted skipped dienes bearing a C3 stereogenic center, generally with outstanding enantioselectivities (up to 99.5:0.5 er). This is the first catalytic enantioselective allylic alkylation of phosphonates, and the overall process represents a formal enantioselective α-C(sp2)-H allylic alkylation of α,β-unsaturated carbonyls and acrylonitrile.

Cyclic Sulfoxonium Ylides: Synthesis and Chemospecific Reactivity in the Catalytic Alkylation of Indoles

AbstractThe study of the reactivity of cyclic sulfoxonium ylides has been so far neglected, in particular for reactions that forms carbon‐carbon bond at the ylide carbon atom. Herein, we describe the synthesis of cyclic sulfoxonium ylides by palladium‐catalyzed intramolecular arylation and the reactivity of these ylides in the C3‐alkylation of indoles in the presence of either an acid catalyst or an iridium catalyst. This study revealed that acid catalysis is only efficient for cyclic sulfoxonium ylides in which the tether is a six‐membered lactone, whereas iridium catalysis was better suited to the reaction of cyclic sulfoxonium ylides in which the tether is a five‐membered ring ketone or lactone. The observed chemospecificity might be due to the relative basicity of the ylides under acid catalysis and to the steric hindrance around an iridium carbene intermediate when the reaction is conducted with the iridium catalyst.

Mechanistic insight into the photocatalytic N-alkylation of piperazine with alcohols over TiO2 supported Pd catalysts

N-alkylated piperazines can be synthesized by the thermal catalytic alkylation of piperazine with alkyl halides or alcohols in the presence of supported metal catalysts. However, these processes either discharge large amounts of waste or require harsh conditions. Here, we report the results of N-alkylation of piperazine with lower alcohols (methanol, ethanol, and propanol) without external hydrogen addition at room temperature in the presence of a TiO2-supported Pd catalyst (Pd/TiO2-P) prepared by photodeposition method. Compared with the catalysts prepared by the conventional chemical reduction or hydrogen reduction, the Pd/TiO2-P catalyst showed the highest conversion of piperazine and the best selectivity to N-alkypiperazines. The mechanistic studies indicated that this phenomenon occurs via tandem photocatalytic reactions involving alcohol dehydrgenation to aldehyde, aldehyde condensation with piperazine to enamine, and enamine hydrogenation to N-alkylated piperazines. Considering the experimental results of methanol isotope kinetics, the α-C–H cleavage of methanol to form hydroxymethyl radical (·CH2OH) was proven to be the rate-determining step in the N-alkylation reaction of piperazine with low carbon alcohols. The characterization and control experiments revealed that the size of Pd nanoparticles and the valence of Pd species were vital to the reaction. The Pd/TiO2-P catalyst with an average of 2.5 ± 0.5 nm Pd particles and approximately 68% Pd0 species on surfaces presented the highest activity for the photocatalytic tandem reactions of methanol dehydrogenation and enamine hydrogenation.