Electron-deficient Alkenes Research Articles

2-Silylated Dihydroquinazolinone as Photocatalytic Energy Transfer Enabled Radical Hydrosilylation Reagent.

The hydrosilylation of alkenes is one of the most important methods for the synthesis of organosilicon compounds. In addition to the platinum-catalyzed hydrosilylation, silyl radical addition reactions are notable as economic reactions. We have developed an efficient and widely applicable silyl radical addition reaction by using 2-silylated dihydroquinazolinone derivatives under photocatalytic conditions. Electron-deficient alkenes and styrene derivatives underwent hydrosilylation to give addition products in good to high yields. Mechanistic studies indicated that the photocatalyst functioned not as a photoredox catalyst but as an energy transfer catalyst. DFT calculations clarified that the triplet excited state of 2-silylated dihydroquinazolinone derivatives released a silyl radical through the homolytic cleavage of a carbon-silicon bond, and this was followed by the hydrogen atom transfer pathway, not the redox pathway.

Synthesis of New Dehydrodieugenol Derivatives via Olefin Cross Metathesis and In Vitro Evaluation of Their Trypanocidal Activity

Ruthenium-catalyzed cross metathesis using biseugenol (1) with electron-deficient olefins methyl (2a) and ethyl (2b) acrylates, acrylic acid (2c), acrylonitrile (2d), and methyl methacrylate (2e) derivatives have been conducted to afford respective derivatives 3a–3e with good yields and excellent conversion rates. Activity of prepared compounds against trypomastigote and amastigote forms of Trypanosoma cruzi and mammalian cytotoxicity have been evaluated. The results obtained indicate that the IC50 values for amastigotes of compounds 3b and 3d are quite similar to those of biseugenol (1), but unlike this compound, they show reduced toxicities with SI values similar to those of the standard drug benznidazol.

Phosphine-Catalyzed [3+2] Annulation of Hepta-2,3,5-trienedioates with Alkenes for the Construction of Exocyclic Olefinic Cyclopentenes.

Hepta-2,3,5-trienedioates 1 have been employed as substrates to explore Lewis base-catalyzed annulation reactions. This leads to the discovery of a phosphine-catalyzed [3+2] annulation of 1 with electron-deficient alkenes for the construction of exocyclic olefinic cyclopentenes in good yields and moderate E:Z ratios under mild conditions. The annulation is believed to proceed in a tandem [3+2] cyclization and double bond migration in which the ε-ester is crucial to both processes. This reaction also showcases a substrate-controlled divergent reactivity compared to that of a previous report.

Metal-Free Photoredox Four-Component Strategy to 1,3-Functionalized BCP Derivatives.

Trifluoromethyl bicyclo[1.1.1]pentanes (BCPs) have attracted significant attention from the scientific community and pharmaceutical industries due to their advantageous physicochemical properties as arene bioisosteres. Initial photoredox perfluoroalkylation of [1.1.1]propellane triggers the tandem reaction to the perfluoroalkyl BCP radical followed by Giese addition to an in situ generated electron-deficient alkene by Knoevenagel condensation in a four-component fashion to form 1,3-functionalized BCPs. This strategy provides easy access to various 1,3-functionalized perfluoroalkyl BCP derivatives with the added advantage of nitrile group as a functional handle to diversified transformations. This methodology offers scalability and late-stage derivatization of drug molecules with high chemoselectivity.

Synthesis of Functionalized Tetrahydroquinoline Containing Indole Scaffold via Chemoselective Annulation of Aza-ortho-quinone Methide Precursor.

The chemoselective annulation of aza-ortho-quinone methide generated by in situ o-chloromethyl sulfonamide has been achieved with bifunctional acyclic olefin. This efficient approach provides access to the diastereoselective synthesis of functionalized tetrahydroquinoline derivatives containing indole scaffolds through the inverse-electron-demand aza-Diels-Alder reaction under mild reaction conditions with excellent results (up to 93% yield, > 20:1 dr). Moreover, this article realized the cyclization of α-halogeno hydrazone with electron-deficient alkene affording the tetrahydropyridazine derivatives, which had never been reported.

Air-tolerant, ligand-free nickel-catalyzed, manganese-assisted reductive Heck reaction of alkyl/aryl halides with electron-deficient olefins

An air-tolerant reductive Heck reaction of alkyl/aryl halides with α, β-unsaturated esters, nitriles and amides catalyzed by simple nickel bromide has been developed by using manganese as reductant in refluxing acetonitrile. Water plays a double-face role in the catalytic process, hydrolysis of the enolate and/or C-tautomer intermediates to afford the conjugate adducts while suppressing the catalysis at high concentration. The scope and limitations of the nickel-catalyzed manganese-mediated process have been demonstrated by more than 40 examples, showing large steric effects and good functional group compatibility except for reduction-sensitive ones.

Migration from Photochemistry to Electrochemistry for [2 + 2] Cycloaddition Reaction.

Cyclobutane scaffolds are incorporated in several valuable natural and bioactive products. However, non-photochemical ways to synthesize cyclobutanes have scarcely been investigated. Herein, based on the principles of the electrosynthesis technique, we introduce a novel electrochemical approach for attaining cyclobutanes by a simple [2 + 2] cycloaddition of two electron-deficient olefins in the absence of photocatalysts or metal catalysts. This electrochemical strategy provides a suitable condition for synthesizing tetrasubstituted cyclobutanes with a variety of functional groups in good to excellent efficiency, compatible with gram-scale synthesis. In contrast to previous challenging methods, this approach strongly focuses on the convenient accessibility of the reaction instruments and starting materials for preparing cyclobutanes. Readily accessible and inexpensive electrode materials are firm evidence to prove the simplicity of this reaction. In addition, mechanistic insight into the reaction is obtained by investigation of the CV spectra of the reactants. Also, the structure of a product is identified by X-ray crystallography.

Minimalist Design for Solar Energy Conversion: Revamping the π-Grid of an Organic Framework into Open-Shell Superabsorbers.

We apply a versatile reaction to a versatile solid: the former involves the electron-deficient alkene tetracyanoethylene (TCNE) as the guest reactant; the latter consists of stacked 2D honeycomb covalent networks based on the electron-rich β-ketoenamine hinges that also activate the conjugated, connecting alkyne units. The TCNE/alkyne reaction is a [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) that forms strong push-pull units directly into the backbone of the framework-i.e., using only the minimalist "bare-bones" scaffold, without the need for additional side groups of alkynes or other functions. The ability of the stacked alkyne units (i.e., as part of the honeycomb mass) to undergo such extensive rearrangement highlights the structural flexibility of these covalent organic framework (COF) hosts. The COF solids remain porous, crystalline, and air-/water-stable after the CA-RE modification, while the resulting push-pull units feature distinct open-shell/free-radical character, are strongly light-absorbing, and shift the absorption ends from 590 nm to around 1900 nm (band gaps from 2.17-2.23 to 0.87-0.95 eV), so as to better capture sunlight (especially the infrared region which takes up 52% of the solar energy). As a result, the modified COF materials achieve the highest photothermal conversion performances, holding promise in thermoelectric power generation and solar steam generation (e.g., with solar-vapor conversion efficiencies >96%).

Photoexcited NiII-Aryl Complex-Mediated Giese Reaction of Aryl Bromides.

A Giese reaction of aryl bromides with electron-deficient alkenes was developed, enabled by a dual catalyst system containing NiII complex and IrIII photocatalyst. This protocol could accommodate a variety of aryl bromides and electron-deficient alkenes, delivering the conjugate adducts in up to 97% yield. The utilization of photoexcited (dtbbpy)NiII(aryl)Br intermediate as an aryl radical source allows this novel transformation of aryl halides, thus expanding the chemical space of excited nickel catalysis.

Diverse Synthesis of Fused Polyheterocyclic Compounds via [3 + 2] Cycloaddition of In Situ-Generated Heteroaromatic N-Ylides and Electron-Deficient Olefins.

[3 + 2] Cycloaddition reactions of heteroaromatic N-ylides with electron-deficient olefins have been developed. The heteroaromatic N-ylides, in situ generated from N-phenacylbenzothiazolium bromides, can smoothly react with maleimides under very mild conditions, affording fused polycyclic octahydropyrrolo[3,4-c]pyrroles in good-to-excellent isolated yields. This reaction concept could also be extended to 3-trifluoroethylidene oxindoles and benzylidenemalononitriles as electron-deficient olefins for accessing highly functionalized polyheterocyclic compounds. A gram-scale experiment was also carried out to verify the practicability of the methodology.

Enhanced Excited-State Hydricity of Pd-H Allows for Unusual Head-to-Tail Hydroalkenylation of Alkenes.

Photoinduced enhancement of hydricity of palladium hydride species enables unprecedented hydride addition-like ("hydridic") hydropalladation of electron-deficient alkenes, which allows for chemoselective head-to-tail cross-hydroalkenylation of electron-deficient and electron-rich alkenes. This mild and general protocol works with a wide range of densely functionalized and complex alkenes. Notably, this approach also allows for highly challenging cross-dimerization of electronically diverse vinyl arenes and heteroarenes.

AIE active luminous dye with a triphenylamine attached benzothiazole core as a portable polymer film for sensitively detecting CN- ions in food samples

Aggregation-induced emission (AIE) active 3-(3-(benzo[d]thiazol-2-yl)-2-hydroxyphenyl)-2-(4'-(diphenylamino)-[1,1′-biphenyl]-4-yl)acrylonitrile (BTPA) has been designed and synthesized herein, with the goal of detecting CN− ions at a low-level in semi–aqueous medium. The deliberate addition of the electron-deficient alkene BTPA increased its sensitivity and selectivity to CN− ions, with a better detection limit of 6.4 nM, unveiling the next-generation approach to creating sophisticated CN− ions selective chemosensors. The ESI-MS and NMR spectra analyses provided strong support for the structures of the chemosensors, while the UV–Vis, photoluminescence, and 1H-NMR titration experiments provided support for the sensing efficiencies. Subsequently, PVDF/BTPA electrospun nanofibers have been effectively produced as functional films. These nanofiber films exhibit outstanding mechanical strength, photo/thermal stability, and optical responsiveness to CN− ions, making them a potential choice for on-field emerging contaminant detection.

Decatungstate-Catalyzed C(sp3)–H Alkylation of a Val Residue Proximal to the N-Terminus Controlled by an Electrostatic Interaction

The decatungstate photocatalyst [W10O32]4- efficiently promoted the C(sp3)-H alkylation of the trifluoroacetic acid salt of valine methyl ester (H-Val-OMe·TFA) with electron-deficient alkenes under UV irradiation. The electrostatic interaction between the cationic ammonium group (+NH3) of the main chain and anionic [W10O32]4- played an important role in this reaction. The influence of various protected amino acids in the C(sp3)-H alkylation was investigated as the model reaction for the alkylation of Val-containing peptides. The introduction of an alkyne moiety into Val through this alkylation was successful, and successive copper-catalyzed azide-alkyne cycloaddition (CuAAC) was demonstrated. The C(sp3)-H bond of a Val residue located at the second from the N-terminus was also successfully converted. C(sp3)-H alkylation of oligopeptides containing two Val residues selectively proceeded proximally to the N-terminus.

Synthesis and Characterization of Tetraphenylethene AIEgen-Based Push-Pull Chromophores for Photothermal Applications: Could the Cycloaddition-Retroelectrocyclization Click Reaction Make Any Molecule Photothermally Active?

Three new tetraphenylethene (TPE) push-pull chromophores exhibiting strong intramolecular charge transfer (ICT) are described. They were obtained via [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) click reactions on an electron-rich alkyne-tetrafunctionalized TPE (TPE-alkyne) using both 1,1,2,2-tetracyanoethene (TCNE), 7,7,8,8-tetracyanoquinodimethane (TCNQ) and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) as electron-deficient alkenes. Only the starting TPE-alkyne displayed significant AIE behavior, whereas for TPE-TCNE, a faint effect was observed, and for TPE-TCNQ and TPE-F4-TCNQ, no fluorescence was observed in any conditions. The main ICT bands that dominate the UV-Visible absorption spectra underwent a pronounced red-shift beyond the near-infrared (NIR) region for TPE-F4-TCNQ. Based on TD-DFT calculations, it was shown that the ICT character shown by the compounds exclusively originated from the clicked moieties independently of the nature of the central molecular platform. Photothermal (PT) studies conducted on both TPE-TCNQ and TPE-F4-TCNQ in the solid state revealed excellent properties, especially for TPE-F4-TCNQ. These results indicated that CA-RE reaction of TCNQ or F4-TCNQ with donor-substituted are promising candidates for PT applications.

Lewis-Base-Catalyzed Enantioselective Formal [4 + 2] Annulations of Morita–Baylis–Hillman Carbonates: Access to Tetrahydroquinolines Derivatives

The Lewis-base-catalyzed enantioselective formal [4 + 2] annulation reaction of o-acylamino-aryl MBH carbonates and electron-deficient olefins was developed. Tetrahydroquinolines with three sequential stereogenic centers containing a quaternary stereocenter were obtained in high yields with good enantioselectivity.

Sequential Modifications of Metal-Organic Layer Nodes for Highly Efficient Photocatalyzed Hydrogen Atom Transfer.

Herein, we report the synthesis of a bifunctional photocatalyst, Zr-OTf-EY, through sequential modifications of metal cluster nodes in a metal-organic layer (MOL). With eosin Y and strong Lewis acids on the nodes, Zr-OTf-EY catalyzes cross-coupling reactions between various C-H compounds and electron-deficient alkenes or azodicarboxylate to afford C-C and C-N coupling products, with turnover numbers of up to 1980. In Zr-OTf-EY-catalyzed reactions, Lewis acid sites bind the alkenes or azodicarboxylate to increase their local concentrations and electron deficiency for enhanced radical additions, while EY is stabilized by site isolation on the MOL to afford a long-lived catalyst for hydrogen atom transfer. The proximity between photostable EY sites and Lewis acids on the nodes of Zr-OTf-EY enhances the catalytic efficiency by approximately 400 times over the homogeneous counterpart in the cross-coupling reactions.

Development of Practical Synthetic Methods Utilizing O-X or N-X Species

In chemical species containing of oxygen-halogens and nitrogen-halogens bonds, the halogen substituents show versatile reactivities, because oxygen and nitrogen atoms have higher electronegativity than halogen elements except for fluorine. I have focused on such monovalent halogen species and developed various synthetic methods utilizing O-X and N-X bonds which involves ionic and radical reactions. In this account, I describe such practical synthetic methodologies, which are CO2 fixation to unsaturated alcohols and amines, oxidative homo- and cross-coupling reactions of aromatic amines, novel generation of nitrile oxides from aldoximes, synthesis of oxazole-fused C60, iodoamination of alkenes in water, diaziridination of secondary amines, diastereodivergent diamination of unactivated alkenes, practical aziridination of electron-deficient alkenes, selective synthesis of nitrogen-bridged fullerenes, and benzylic C-H amidation.

Visible light-promoted alkylation of electron-deficient alkenes with alkylsilyl peroxides

We report a photochemical approach for the generation of alkyl radicals from alkylsilyl peroxides (ASPs) in the absence of any transition metal or photocatalyst. This operationally simple protocol utilizes Hantzsch ester as a photoreductant to efficiently induce the OO bond cleavage of various ASPs via single-electron transfer, generating the corresponding alkyl radicals under mild conditions. The radicals generated by this method participate in a Giese-type addition with a wide range of electron-deficient alkenes. This study broadens the methods by which radicals can be generated from ASPs, and thus improves their applicability and versatility in the field of radical chemistry.

Catalyst-Tuned Regiodivergent and Enantioselective Formal Hydroaminations of Acryamides to α-Tertiary-α-Aminolactam and β-Aminoamide Derivatives.

Enantioenriched α-tertiary-α-aminoacid and α-chiral-β-aminoacid derivatives play an important role in biological science and pharmaceutical chemistry. Thus, the development of methods for their synthesis is highly valuable yet remains challenging. Herein, an unprecedented catalyst-controlled regiodivergent and enantioselective formal hydroamination of 1,1-disubstituted acrylamides with aminating agents has been developed, accessing enantioenriched α-tertiary-α-aminolactam and α-chiral-β-aminoamide derivatives. Conceptually, sterically-disfavoured and electronically-disfavoured enantioselective hydroamination of electron-deficient alkenes have been successfully tuned using different transition metals and chiral ligands. Notably, extremely steric congested aliphatic α-tertiary-α-aminolactam derivatives were synthesized by Cu-H catalyzed asymmetric forge of C-N bond with tertiary alkyl species for the first time. Enantioenriched α-chiral-β-aminoamide derivatives have been accessed by Ni-H catalyzed anti-Markovnikov-selective formal hydroaminations of alkenes. This set of reactions tolerates a wide range of functional groups to deliver diverse α-tertiary-α-aminolactam and α-chiral-β-aminoamide derivatives in good yields with high levels of enantioselectivity.

Hydrogen-Atom-Transfer-Initiated Radical/Polar Crossover Annulation Cascade for Expedient Access to Complex Tetralins.

A radical/polar crossover annulation between allyl-substituted arenes and electron-deficient alkenes is described. Cobalt-catalyzed hydrogen atom transfer (HAT) facilitates tandem radical C-C bond formation that generates functionalized tetralin products in the face of potentially problematic hydrofluorination, hydroalkoxylation, hydrogenation, alkene isomerization, and radical polymerization reactions. The reactions proceed under mild conditions that tolerate many functional groups, leading to a broad substrate scope. This powerful ring-forming reaction very quickly assembles complex tetralins that are the formal products of the largely infeasible Diels-Alder cycloadditions of styrenes.