Reduction Of Alkenes Research Articles

Photocatalysis Meets Copper Catalysis: A New Opportunity for Asymmetric Multicomponent Radical Cross-Coupling Reactions.

ConspectusIn recent years, radical-mediated cross-coupling reactions have emerged as a compelling strategy for achieving a rich diversity in molecular topologies under benign conditions. However, the inherent high reactivity of radicals presents considerable challenges in controlling reaction pathways and selectivity, which often results in a limited range of substrates and a constrained reaction profile. Given the capacity of visible-light photoredox catalysis to generate a wide variety of reactive radicals and radical ions in a controlled manner and the propensity of copper complexes toward radical species, we envisaged that the synergy between chiral copper catalysts and photoactive catalysts would pave the way for developing innovative strategies. This integration is poised to unlock a broad spectrum of enantioselective multicomponent radical cross-coupling reactions.In this Account, we describe our insights and recent efforts in the realm of enantioselective multicomponent radical cross-coupling reactions. These advancements have been achieved through the innovative application of dual photoredox/copper catalysis or bifunctional copper catalysis under visible light irradiation. Our work is systematically divided into two sections based on the activation modes. The first section focuses on photoinduced copper-catalyzed chiral C-C and C-O bond formation through a radical addition/nucleophilic trap sequence. Our discussion of chiral C-C bond formation is particularly concentrated on the asymmetric carbocyanation and carboarylation of vinylarenes, 1,3-enynes, and 1,3-dienes. Our findings underscore that irradiation with visible light can adeptly modulate the pace of radical generation, thus orchestrating consecutive reaction stages and ensuring the attainment of both chemo- and stereoselectivity. In the domain of chiral C-O bond formation, leveraging carboxylic acids as a nucleophilic oxygen source, we introduce a suite of esterification reactions of benzylic, allylic, and propargylic radicals. These radicals are derived from a variety of radical precursors, showcasing the versatility of our approach. The following section highlights our innovative discovery in the field of dual photoredox/copper catalysis, which enables enantioselective three-component radical transformations via the direct activation of aromatic alkenes. This methodology begins with the generation of formal distonic radical anions through the photocatalytic single-electron reduction of aromatic alkenes, thus, enabling orthogonal reactivity. Employing H2O, D2O, and CO2 as external electrophile agents, we have developed three types of radical cyanofunctionalization reactions: hydrocyanation, deuteriocyanation, and cyanocarboxylation. These reactions provide practical access to diversely functionalized chiral nitriles with high enantiomeric excess.Collectively, these synthetic methodologies highlight the immense potential inherent in the synergistic integration of photocatalysis and asymmetric copper catalysis. This Account aspires to deepen our comprehension of the advantages conferred by these catalytic systems, elucidating the crucial role of photocatalysis in facilitating enantioselective multicomponent radical cross-couplings. We anticipate that this Account will provide valuable insights and stimulate the evolution of innovative methodologies within this rapidly expanding field.

Synchronous photocatalytic benzimidazole formation and olefin reduction by magnetic separable visible-light-driven Pd-g-C3N4-Vanillin@γ-Fe2O3-TiO2 Nanocomposite

A visible light-responsive magnetically separable photocatalyst Pd-g-C3N4-Vanillin@γ-Fe2O3-TiO2 is fabricated using vanillin as a natural junction under ultrasonic agitation. Structural, morphological, optical, thermal, and magnetic assessments of the as-prepared catalyst are carried out. The photocatalyst successfully drives the simultaneous benzimidazole formation, and olefin hydrogenation with high atom economy under blue LED light and mild conditions. The photocatalytic activity of Pd-g-C3N4-Vanillin@γ-Fe2O3-TiO2 is significantly affected by the γ-Fe2O3:TiO2 weight ratio. PL spectra revealed the effective separation of carriers in the fabricated catalyst promoting its photocatalytic activity. The action spectra using the apparent quantum efficiency (AQE) exhibited the maximum AQEs at 520 and 750 nm in which the highest performance for styrene hydrogenation is observed. The title magnetically separable heterogeneous photocatalyst provides high yields of products under perfectly safe visible light, produces low/zero waste, and avoids using an external high-pressure hydrogen gas source, harmful solvents, undesirable additives, and reducing agents rendering green conditions for chemical reactions.

Chiral Organic Salt Supported Pd Nanoparticles as Selective Heterogeneous Catalysts of Hydrogenation Reactions

AbstractIn this study, we report the synthesis of a new type of chiral crystalline organic porous salt CF2 derived from the ionic reaction between tetrakis(4‐sulfophenyl)methane (TSPM) and the tetra‐(S)‐prolylamide of tetrakis(4‐aminophenyl)methane, (S)‐TPPM, and its ability to stabilize 2 nm palladium nanoparticles to give a novel, nonpyrophoric, chiral, catalytic material Pd@CF2. The preparation of the catalyst was very simple and conducted in water. The heterogeneous catalytic performance of Pd@CF2 was tested in hydrogen reductions of olefins and substituted nitroaromatic compounds using Pd/C as a comparison to determine the specific features of the novel catalyst. Although both types of catalysts exhibited similar catalytic activity in case of reductions of diphenylacetylene and nitrobenzene, Pd@CF2 predominantly promoted the reduction of p‐nitrobenzaldehyde to p‐aminobenzyl alcohol whereas Pd/C gave p‐toluidine. The reduction of p‐dinitrobenzene led to predominant formation of p‐nitrophenylhydroxylamine if promoted by the novel catalyst and to a mixture of products if promoted by Pd/C. In addition, the introduction of p‐alkoxy groups onto nitrobenzenes slowed down the reduction with Pd@CF2 but had no influence on Pd/C activity. A hypothesis ascribing these observations to dissimilar equilibrium distributions of nitro and polar groups within the organic framework and the palladium metal surface is proposed to rationalize the selectivity of the novel catalytic material.

Photocatalytic generation of alkyl carbanions from aryl alkenes

AbstractOrganometallic reagents are routinely used as fundamental building blocks in organic chemistry to rapidly diversify molecular fragments via carbanion intermediates. However, the catalytic generation of carbanion equivalents, particularly from sp3-hybridized alkyl scaffolds, remains an underdeveloped goal in chemical synthesis. Here we disclose an approach for the generation of alkyl carbanions via single-electron reduction of aryl alkenes, enabled by multi-photon photoredox catalysis. We demonstrate that photocatalytically induced alkyl carbanions engage in intermolecular C–C bond-forming reactions with carbonyl electrophiles. Central to this method is the controlled formation of an alkene distonic radical anion intermediate that undergoes nucleophilic addition, followed by a kinetically favoured reductive polar crossover to produce a second carbanion available for further diversification. The versatility of this protocol was illustrated by the development of four distinct intermolecular C–C bond-forming reactions with aromatic alkenes (hydroalkoxylation, hydroamidation, aminoalkylation and carboxyaminoalkylation) to generate a range of valuable and complex scaffolds.

β,β‐Disubstituted Alkan‐2‐ones from Propargylic Alcohols Combining a Meyer‐Schuster Rearrangement and Asymmetric Alkene Bioreduction

AbstractThe combination of a gold(I) N‐heterocyclic carbene complex and an ene‐reductase (ERED) has made possible the synthesis of enantiopure β,β‐disubstituted ketones in a one‐pot concurrent approach. The protocol consists of the Meyer‐Schuster rearrangement of racemic propargylic tertiary alcohols using [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]‐[bis(trifluoromethanesulfonyl)‐imide]gold(I) (IPrAuNTf2), followed by an asymmetric alkene reduction of the α,β‐unsaturated ketone intermediate using the Zymomonas mobilis ERED (NCR‐ERED). The chemoenzymatic cascade was optimised with a model substrate, where E/Z‐isomers both generated the (R)‐ketone, which was rationalised using in silico molecular docking experiments. The cascade was then applied towards the production of a series of (R)‐4‐substituted‐alkan‐2‐ones in enantiopure form in a straightforward manner.

Generation of alkene radical cation for thioxanthone-TfOH complex-catalyzed intramolecular cyclization using a photoredox catalysis strategy

Photo catalysis has comprehensively become a powerful tool in organic synthesis, and organic molecules are thriving as catalyst. The thioxanthone-TfOH complex (9-HTXTF) as photoredox catalyst with high oxidative capacity can be applied in single electron reduction of alkene affording alkene radical anion as a key intermediate. To transform this intermediate from radical anion to radical cation, a well-designed strategy is proposed with N-arylacrylamides as substrate. Based on its single electron transfer (SET) with 9-HTXTF*, N-radical cation is generated and then transformed to alkene radical cation by intramolecular conjugated system. By using this photoredox catalysis strategy, we developed a 9-HTXTF-catalyzed photochemical cyclization of alkenes, which further expands the applications of this catalyst. The entire cyclization is metal-free and without sacrificing agents, which conforms to atom economy and environmental friendliness.

Woollins’ Reagent: A Graphical Review of Its Main Synthetic Uses

AbstractWoollins’ reagent (W.R.) was initially used for the selenation of carbonyl compounds. However, various synthetic applications utilizing this reagent have since been discovered, making it increasingly useful. Examples include the formation of heterocycles, the stereospecific reduction of olefins, and the synthesis of selenoic acids, among others. Consequently, synthetic studies of W.R. derivatives have become increasingly relevant due to the growing demand for selenated compounds in various applications. Two notable examples are the agricultural sector, with the development of pesticides, and the pharmaceutical sector, with the development of antivirals, antioxidants, and neuroprotectors, among others. Hence, this graphical review aims to address the synthetic diversity that W.R. can provide, presenting examples of its main synthetic uses.

H2-driven biocatalysis for flavin-dependent ene-reduction in a continuous closed-loop flow system utilizing H2 from water electrolysis

Despite the increasing demand for efficient and sustainable chemical processes, the development of scalable systems using biocatalysis for fine chemical production remains a significant challenge. We have developed a scalable flow system using immobilized enzymes to facilitate flavin-dependent biocatalysis, targeting as a proof-of-concept asymmetric alkene reduction. The system integrates a flavin-dependent Old Yellow Enzyme (OYE) and a soluble hydrogenase to enable H2-driven regeneration of the OYE cofactor FMNH2. Molecular hydrogen was produced by water electrolysis using a proton exchange membrane (PEM) electrolyzer and introduced into the flow system via a designed gas membrane addition module at a high diffusion rate. The flow system shows remarkable stability and reusability, consistently achieving >99% conversion of ketoisophorone to levodione. It also demonstrates versatility and selectivity in reducing various cyclic enones and can be extended to further flavin-based biocatalytic approaches and gas-dependent reactions. This electro-driven continuous flow system, therefore, has significant potential for advancing sustainable processes in fine chemical synthesis.

Radical Carbocyclization Intercepted Reductive C‐C Bond Formation Between 1,n‐Enynes or Dienes and Electron‐Poor Olefins/Alkynes

Metal hydride catalyzed hydrogen atom transfer (MHAT) reaction of 1,6‐enyne and electron‐poor alkene progresses through a radical cascade, involving ene‐yne cyclization and exocyclic C‐C bond formation superseding the direct reductive olefin cross‐coupling; which is realized in the current study. The generality of this reaction manifold is demonstrated with a range of functionalized 1,6‐enyne and dienes and involving structurally distinct electron‐poor olefins and alkynes as partners. Current work unveils a merger of MHAT‐based olefin‐hydro functionalization with radical ene‐one cyclization.

Wintertime ozone surges: The critical role of alkene ozonolysis

Ozone (O3) pollution is usually linked to warm weather and strong solar radiation, making it uncommon in cold winters. However, an unusual occurrence of four high O3 episode days (with maximum hourly concentrations exceeding 100 ppbv and peaking at 121 ppbv) was recorded in January 2018 in Lanzhou city, China. During these episodes, the average daytime concentration of total non-methane volatile organic compounds (TVOCs) reached 153.4 ± 19.0 ppbv, with alkenes—largely emitted from the local petrochemical industry—comprising 82.3 ± 13.1 ppbv. Here we show a photochemical box model coupled with a Master Chemical Mechanism to elucidate the mechanisms behind this unusual wintertime O3 pollution. We find that the typically low temperatures (−1.7 ± 1.3 °C) and weak solar radiation (263.6 ± 60.7 W m-2) of those winter episode days had a minimal effect on the reactivity of VOCs with OH radicals. Instead, the ozonolysis of alkenes generated Criegee intermediates, which rapidly decomposed into substantial ROx radicals (OH, HO2, and RO2) without sunlight. This radical production led to the oxidation of VOCs, with alkene ozonolysis ultimately contributing to 89.6 ± 8.7% of the O3 formation during these episodes. This mechanism did not activate at night due to the depletion of O3 by the NO titration effect. Furthermore, the findings indicate that a reduction of alkenes by 28.6% or NOx by 27.7% in the early afternoon could significantly mitigate wintertime O3 pollution. Overall, this study unravels the unique mechanism of alkene-induced winter O3 pollution and offers a reference for winter O3 reduction strategies in the petrochemical industrial regions.

Bio-electrocatalytic Alkene Reduction Using Ene-Reductases with Methyl Viologen as Electron Mediator.

Asymmetric hydrogenation of alkene moieties is important for the synthesis of chiral molecules, but achieving high stereoselectivity remains a challenge. Biocatalysis using ene-reductases (EReds) offers a viable solution. However, the need for NAD(P)H cofactors limits large-scale applications. Here, we explored an electrochemical alternative for recycling flavin-containing EReds using methyl viologen as a mediator. For this, we built a bio-electrocatalytic setup with an H-type glass reactor cell, proton exchange membrane, and carbon cloth electrode. Experimental results confirm the mediator's electrochemical reduction and enzymatic consumption. Optimization showed increased product concentration at longer reaction times with better reproducibility within 4-6 h. We tested two enzymes, Pentaerythritol Tetranitrate Reductase (PETNR) and the Thermostable Old Yellow Enzyme (TOYE), using different alkene substrates. TOYE showed higher productivity for the reduction of 2-cyclohexen-1-one (1.20 mM h-1), 2-methyl-2-cyclohexen-1-one (1.40 mM h-1) and 2-methyl-2-pentanal (0.40 mM h-1), with enantiomeric excesses ranging from 11 % to 99 %. PETNR outperformed TOYE in terms of enantioselectivity for the reduction of 2-methyl-2-pentanal (ee 59 % ± 7 % (S)). Notably, TOYE achieved promising results also in reducing ketoisophorone, a challenging substrate, with similar enantiomeric excess compared to published values using NADH.

Mild Photochemical Reduction of Alkenes and Heterocycles via Thiol-Mediated Formate Activation.

The reduction of alkenes to their respective alkanes is one of the most important transformations in organic chemistry, given the abundance of natural and commercial olefins. Metal-catalyzed hydrogenation is the most common way to reduce alkenes; however, the use of H2 gas in combination with the precious metals required for these conditions can be impractical, dangerous, and expensive. More complex substrates often require extremely high pressures of H2, further emphasizing the safety concerns associated with these hydrogenation reactions. Here we report a safe, cheap, and practical photochemical alkene reduction using a readily available organophotocatalyst, catalytic thiol, and formate. These conditions reduce a variety of di-, tri-, and tetra-substituted alkenes in good yield as well as dearomatize pharmaceutically relevant heterocycles to generate sp3-rich isosteres of benzofurans and indoles. These formal-hydrogenation conditions tolerate a broad range of functionalities that would otherwise be sensitive to typical hydrogenations and are likely to be important for industry applications.

Bridging Homogeneously and Heterogeneously Catalyzed Higher‐Alcohol Synthesis via Cobalt‐Based Catalysts

AbstractIndustrial implementation of the heterogeneously catalyzed CO hydrogenation to higher alcohols is highly desired, but deeper insights into the reaction mechanisms and active sites are still needed. This review summarizes the established and well‐investigated cobalt‐based catalysts and the mechanisms resulting in oxygenate formation. Recently, a cobalt‐based system derived from Mn‐Co‐based Prussian blue analogs by pyrolysis has shown great potential for higher‐alcohol synthesis. In addition to the heterogeneously catalyzed reaction pathways involved in Fischer‐Tropsch synthesis and methanol synthesis, the homogeneously catalyzed reaction pathways like reductive olefin hydroformylation and reductive primary alcohol carbonylation were found to play a key role.

Effects of VOC emission reduction on atmospheric photochemistry and ozone concentrations during high-ozone episodes

We studied atmospheric volatile organic compounds (VOCs) characteristics and sources during fifteen high ozone (O3) episodes (daily 1-h maximum >100 ppbv and maximum 8-h average > 80 ppbv) in Nanjing, China, and used a photochemical box model to study the O3 formation sensitivity of VOCs, O3 photochemistry, radical budget, and reactivity for different emission reduction scenarios together with the base case ones. Overall, emission reduction from biogenic sources, followed by combustion sources, multiple sources, and solvent usage, had the major impacts on the O3 concentrations. According to photochemical box model simulations, isoprene was the most sensitive or influential VOC in the formation of O3, followed by ethylene, o-xylene, and cis-2-pentene. A 20.6 ± 11.7% concentration reduction of the sixteen most sensitive VOCs (SV16) for the production of O3 could bring the O3 concentration below the national standard level (daily 1-h maximum <100 ppbv). Besides, a 30% emission reduction from all the anthropogenic sources was more than enough to bring the O3 concentration below the national standard level. The total emission reduction of alkenes was always enough to bring the O3 concentration below the national standard level, which was not the case for aromatics under severe pollution conditions. The simulated OH reactivity analysis illustrates the importance of alkenes and aromatics, which account for about half of the total OH reactivity. The highest OH reactivity decreased due to the emission reduction for biogenic sources, followed by combustion and multiple sources. Alkenes played a major role in the OH, HO2, and RO2 radical's formation in the study area. The biggest drop in OH, HO2, and RO2 radical concentrations was noticed for biogenic emission reduction, followed by combustion and multiple sources. Due to the emission reduction from VOC sources, the highest O3 formation rates decreased for biogenic sources, followed by combustion and multiple sources. The acquired information is valuable to the scientific community and policymakers for formulating and implementing O3 pollution control strategies.

Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation

AbstractHerein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C−NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β‐scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol‐containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β‐scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol.

Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation.

Herein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C-NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β-scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol-containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β-scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol.

Inexpensive and mild hydrogenation condition: Raney Ni-catalyzed reduction of alkenes and alkynes using Et3SiH at ambient temperature

The Raney Ni-catalyzed hydrogenation of alkenes and alkynes has been developed. Et3SiH was chosen as the reductant. Substrates with various substituents were reduced at ambient temperature, affording good to excellent yields. No pressure reactor, heating, or inert atmosphere is required and the catalyst can be removed/recycled by simple filtration.

Mechanochemical Birch Reduction with Low Reactive Alkaline Earth Metals.

Birch reduction and similar dissolved metal-type transformations hold significant importance in the organic synthesis toolbox. Historically, the field has been dominated by alkali metal reductants. In this study, we report that largely neglected, low-reactive alkaline earth metals can become powerful and affordable reductants when used in a ball mill under essentially solvent-free conditions, in the presence of ethylenediamine and THF as liquid additives. Calcium can reduce both electron-deficient and electron-rich arenes, with yields of products similar to those obtained with lithium metal. Magnesium reveals enhanced reducing power, enabling the reduction of benzoic acids while keeping electron-rich aromatic moieties intact and allows for chemoselective transformations. The developed mechanochemical approach uses readily available and safer-to-handle metals, operates under air and ambient temperature conditions, and can be used for gram-scale preparations. Finally, we demonstrate that the developed conditions can be used for other dissolved metal-type reductive transformations, including reductive amination, deoxygenation, dehalogenation, alkene and alkyne reductions.

Mechanochemical Birch Reduction with Low Reactive Alkaline Earth Metals

AbstractBirch reduction and similar dissolved metal‐type transformations hold significant importance in the organic synthesis toolbox. Historically, the field has been dominated by alkali metal reductants. In this study, we report that largely neglected, low‐reactive alkaline earth metals can become powerful and affordable reductants when used in a ball mill under essentially solvent‐free conditions, in the presence of ethylenediamine and THF as liquid additives. Calcium can reduce both electron‐deficient and electron‐rich arenes, with yields of products similar to those obtained with lithium metal. Magnesium reveals enhanced reducing power, enabling the reduction of benzoic acids while keeping electron‐rich aromatic moieties intact and allows for chemoselective transformations. The developed mechanochemical approach uses readily available and safer‐to‐handle metals, operates under air and ambient temperature conditions, and can be used for gram‐scale preparations. Finally, we demonstrate that the developed conditions can be used for other dissolved metal‐type reductive transformations, including reductive amination, deoxygenation, dehalogenation, alkene and alkyne reductions.

Mononuclear indium(III) photosensitizers for photo-dehalogenation and olefin reduction.

Photoactive main-group complexes have been relatively underexplored in photocatalytic applications. Herein, we report a family of indium(III) complexes (In-1-In-4) containing pyridylpyrrolide ligands with different amounts of methyl groups, which all exhibit intense visible-light absorption as well as blue-green emission with nanosecond emission lifetimes and emission quantum yields of 6.7-12.5%. Electrochemical studies and quantum chemical calculations indicate that their (photo-)redox processes involve only ligand-centered events, which efficiently mediate photocatalytic dehalogenation and olefin reduction.