Electron-deficient Alkenes Research Articles

Visible Light-Induced Three-Component Alkoxyalkylation of Alkenes with α-Halocarbonyls and Alcohols.

A visible-light-induced three-component alkoxyalkylation of alkenes has been developed under the photocatalysis of fac-Ir(ppy)3. The alkene substrate scope included aryl and aliphatic alkenes as well as electron-rich and electron-deficient alkenes, allowing the facile coupling with a diverse array of α-halocarbonyl compounds. The redox potential-guided orchestration of radical processes with precision allows rapid access to highly functionalized products that are useful building blocks in organic synthesis.

Photoinduced formal [4 + 2] cycloaddition of two electron-deficient olefins and its application to the synthesis of lucidumone.

Electronically mismatched Diels-Alder reaction between two electron-deficient components is synthetically useful and yet underdeveloped under thermal conditions. Herein, a photoinduced formal [4 + 2] cycloaddition of enone with a variety of electron-deficient dienes is described. Key to the success of this stepwise methodology relies on a C - C bond cleavage/rearrangement of the cyclobutane based overbred intermediate via diversified mechanistic pathways. Based on this annulation method, total synthesis of lucidumone is achieved in nine steps.

Photocatalytic C(sp3)-P and C(sp2)-P Bond Formation via a Phosphorus Radical Cation.

A straightforward method for the phosphorylation of electron-deficient alkenes and aryl alkynes has been developed, leading to C(sp3)-P and C(sp2)-P bond formation. This process involves the generation of phosphorus radical cation intermediates through the photocatalyzed oxidation of ethyl diarylphosphinites. The coupling with electron-deficient alkenes encompasses a variety of heteroaromatics, including pyridine, (benzo)thiazole, and benzoxazole, as well as α,β-unsaturated esters and amides. Impressively, the coupling of radical cations with aryl alkynes demonstrated remarkable regioselectivity, thereby facilitating the synthesis of rare α-aryl vinyl phosphine oxides.

Visible-light-mediated cyclopropanation reactions of 3-diazooxindoles with olefins

Visible-light-mediated metal-free cyclopropanation reaction of diazo compounds with different olefins or arenes have been fully developed in recent years. However, electron-deficient olefins still could not be well tolerated in these reactions. Here, by using 3-diazooxindole as the carbene precursor, the visible-light-mediated cyclopropanation reaction of diazo compounds with electron-deficient olefins was successfully developed. The electron-rich olefins were also well tolerated in the reactions. A series of spirocyclopropyloxindoles were synthesized in moderate to high yields under mild, metal-free conditions. Mechanism studies reveal that both singlet and triplet carbenes are probably involved in the reaction.

Visible-Light-Induced Photoredox Construction of Trifluoromethylated Quaternary All-Carbon Centers and Tertiary Alcohols via C(sp3)–Si Bond Cleavage

AbstractThe construction of trifluoromethylated quaternary carbon centers and tertiary alcohols is realized by organo-photoredox catalysis. The process proceeds via visible-light-induced C(sp3)–Si bond cleavage for the generation of α-trifluoromethylated benzyl radicals, which are readily trapped by electron-deficient alkenes with excellent regioselectivity for the construction of trifluoromethylated quaternary all-carbon centers. The α-difluoromethyl counterparts are also suitable for this radical conjugate addition. Furthermore, the in situ oxidation of these α-trifluoromethylated radicals with O2 from air affords tertiary alcohols in high yields, which extends the Fleming–Tamao reaction to tertiary carbon systems.

Palladium-Catalyzed Isomerization/Hydrocarbonylation of Electron-Deficient Alkenes for the Construction of Lactones and Lactams.

An efficient palladium-catalyzed isomerization/hydrocarbonylation of electron-deficient alkenes was developed, affording a variety of benzofuran-2(3H)-ones, dihydrofuran-2(3H)-ones, indolin-2-ones, and isochroman-3-ones in high yields. The reaction exhibits excellent regioselectivity, high atom economy, and a broad range of substrates. The late-stage modification of bioactive molecules and scaled-up reaction demonstrated the practicability of this methodology. Furthermore, the method was employed as the key step for the synthesis of an insulin degrading enzyme (IDE) activator.

Copper-Catalyzed Asymmetric [3 + 2] Cycloaddition of N-2,2,2-Trifluoroethylisatin Ketimines to Access Three Classes of Polyfunctionalized Spiro-Pyrrolidine-Oxindole Motifs.

A facile copper-catalyzed [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with various electron-deficient alkenes to access structurally polyfunctionalized spiro-pyrrolidine-oxindole motifs has been developed. Under the catalytic system, the N-2,2,2-trifluoroethylisatin ketimines could be utilized to react with a series of exocyclic alkenes, including 2-acylamino acrylates, 3-methylene-β-lactams, and sterically hindered cycloalkenes represented by cyclobutenone, to obtain a variety of densely functionalized spiro-pyrrolidine frameworks bearing an α-amino acid ester, β-lactam, and cyclobutanone, respectively, in generally good yields with excellent diastereo- and enantioselectivities.

Triplet Energy Transfer (EnT)-Promoted 1,3-Dipolar Cycloaddition Reactions of N-(Trimethylsilyl)methylphthalimide with Electron-Deficient Alkynes and Alkenes.

Triplet energy transfer (EnT)-promoted photochemical pathways, arisen by visible light and its photosensitizers, have gained significant attention as a complementary strategy for initiating organic transformations in photochemical reactions that are unlikely to occur through a single electron transfer (SET) process. In the present study, we investigated the triplet EnT-promoted 1,3-dipolar cycloaddition reactions of N-(trimethylsilyl)methylphthalimide with electron-deficient alkynyl and alkenyl dipolarophiles. The triplet excited state of N-(trimethylsilyl)methylphthalimide, promoted by the triplet EnT from thioxanthone (TXA) photosensitizer, underwent sequential intramolecular SET and carbon-to-oxygen migration of the silyl group to form azomethine ylide. This generated ylide cycloadded to alkynes or alkenes to regioselectively and stereospecifically produce a nitrogen-containing benzopyrrolizidine scaffold with multiple stereogenic centers. Crucially, the stereoselectivity of these cycloaddition reactions (i.e., endo versus exo addition) was influenced by the nature of the dipolarophiles.

Interaction of 2-unsubstituted imidazole N-oxides with electron-deficient olefins: a quantum chemical analysis

Interaction of 2-unsubstituted imidazole N-oxides with electron-deficient olefins: a quantum chemical analysis

Borane-Catalyzed Enantioselective α-Alkylation of Unactivated 2-Alkylbenzoxazoles with Electron-Deficient Olefins.

Chiral borane-catalyzed reactions have recently emerged as a powerful tool for the enantioselective production of chiral scaffolds. In this study, we demonstrated for the first time that a chiral bisborane catalyst can be used for the α-functionalization of 2-alkylazaarenes; specifically, we accomplished unprecedented highly enantioselective α-alkylation of unactivated 2-alkylbenzoxazoles with electron-deficient olefins. The strong Lewis acidity and the steric bulk of the bisborane catalyst were essential to the observed reactivity and selectivity.

Photoredox Activation of Fluorinated Organozinc Reagents: Hydrofluoroalkylation of Unactivated and Electron Deficient Alkenes.

Hydrofluoroalkylation of alkenes with organozinc reagents under photocatalytic conditions is described. The fluorinated alkyl radicals were generated from organozincs by the single electron oxidation of the carbon-zinc bond. The radical addition step is followed either by hydrogen atom transfer for unactivated olefins or by a reduction/protonation sequence for strongly accepting arylidenemalononitriles.

Thia- and Seleno-Michael Reactions for the Synthesis of Carbonic Anhydrases Inhibitors.

Novel chalcogen-containing amides and esters bearing the benzenesulfonamide moiety have been synthesised upon nucleophilic conjugate addition of thiols and selenols to suitable electron-deficient alkenes. The activity of the synthesised compounds as Carbonic Anhydrases inhibitors has been investigated in vitro and the inhibition mechanism has been elucidated by X-rays studies.

1,3-Difunctionalization of Alkenes by Cobaloxime Photocatalysis.

Represented herein is the first 1,3-difunctionalization of alkenes via photocatalysis. A single cobaloxime is used to carry out two catalytic cycles in which cobaloxime is used not only as a photocatalyst to initiate the reaction but also as a metal catalyst for the β-H elimination process. Electron-deficient alkenes, electron-rich alkenes, and unactivated alkenes could be directly converted to 1,3-bisphosphorylated products, even unsymmetric 1,3-bisphosphorylated products, with only H2 as a byproduct under extremely mild reaction conditions.

Magnesium-Mediated Regioselective Additions of Bromoform to Quinone Methides and Aurone-Derived Azadienes

AbstractThe magnesium-mediated addition of bromoform to conjugated electron-deficient alkenes and imines, such as para-quinone methides (p-QMs) and aurone-derived azadienes, respectively, is reported here for the first time. While p-QMs undergo exclusive and hitherto unreported 1,6-addition of bromoform to afford benzylic tribromomethylated diarylmethanes, aurone-derived azadienes undergo both 1,2- and 1,4-additions to furnish α- and γ-tribromomethylamines. A mechanism involving the intermediacy of the tribromomethyl radical has been proposed based on control experiments and EPR studies. Representative synthetic transformations have also been carried out.

Theoretical insights into enantioselective [2 + 1] cyclopropanation reactions of diazo compounds with electron-deficient olefins.

The cyclopropane skeleton plays a significant role in bioactive molecules due to its distinctive structural properties. This has sparked keen interest and in-depth exploration in the field of stereoselective synthesis of cyclopropane derivatives. In the present study, the mechanism and the origin of stereoselectivity of diastereodivergent synthesis of cyclopropane derivatives via the catalyst-free [2 + 1]-cyclopropanation reactions of 3-diazo-N-methylindole (R1) with two types of electron-deficient olefins (R2 and R3) in both aqueous and toluene media have been studied using the DFT calculations. The findings indicate that these [2 + 1] cycloaddition reactions proceed in two stages, where the first step is not only the rate-determining step but also critically dictates the stereoselectivity of the product. The calculated diastereomeric ratios are in agreement with the experimental results. Furthermore, by utilizing non-covalent interaction (NCI) analysis and energy decomposition analysis based on molecular force fields (EDA-FF), we elucidated that the electrostatic interactions between reactant fragments in the transition state TS1s for the first step are the predominant factors determining the stereoselectivity, as opposed to the experimentally hypothesized steric hindrance and π-π stacking interactions. The geometrical structures of all minima and transition states on the potential energy surface (PES) in solvents water and toluene were fully optimized using the DFT method at the M06-2X(D3)/SMD/6-31 + G(d,p) level of theory. Single-point energy calculations were carried out based on the optimized geometries in the solution at the M06-2X(D3)/6-311 + G(d,p) level. All the DFT calculations were performed using the Gaussian 09 software. The optimized molecular structures were visualized using CYLview software. NCI analysis was performed using the Multiwfn and VMD softwares. The Multiwfn program was also used for CDFT and EDA-FF analyses.

Iron-Catalyzed Three-Component Asymmetric Carboazidation of Alkenes with Alkanes and Trimethylsilyl Azide

AbstractThe fusion of transition-metal catalysis with radical chemistry provides a versatile platform for the asymmetric radical carboazidation of alkenes to enable the rapid assembly of highly functionalized chiral azide compounds. Here, we present an iron-catalyzed asymmetric three-component radical carboazidation that processes electron-deficient alkenes by direct activation of aliphatic C–H bonds. This strategy provides access to a range of valuable chiral azides from readily available chemical feedstocks bearing a tetrasubstituted carbon stereocenter, and their synthetic potential is further showcased through straightforward transformations to provide other valuable enantioenriched building blocks.

Radical-Chain Hydrosilylation of Alkenes Enabled by Triplet Energy Transfer.

Development of mild, robust and metal-free catalytic approach for the hydrosilylation of alkenes is critical to the advancement of modern organosilicon chemistry given their powerful capacity in the construction of various C-Si bonds. Herein, we wish to disclose a visible light-triggered organophotocatalytic strategy, which proceeds via a triplet energy transfer (EnT)-enabled radical chain pathway. Notably, this redox-neutral protocol is capable of accommodating a broad spectrum of electron-deficient and -rich alkenes with excellent functional group compatibility. Electron-deficient alkenes are more reactive and the reaction could be finished within a couple of minutes even in PBS solution with extremely low concentration, which suggests its click-like potential in organic synthesis. The preparative power of the transformations has been further highlighted in a number of complex settings, including the late-stage functionalization and scale-up experiments. Furthermore, although only highly reactive (TMS)3SiH is suitable hydrosilane substrate, our studies revealed the great reactivity and versatility of (TMS)3Si- group in diverse C-Si and Si-Si bond cleavage-based transformations, enabling the rapid introduction of diverse functional groups and the facile construction of valuable quaternary silicon architectures.

Photoinduced Intermolecular Radical Hydroalkylation of Olefins via Ligated Boryl Radicals-Mediated Halogen Atom Transfer.

Light-mediated Halogen-Atom Transfer (XAT) has become a significant methodology in contemporary synthesis. Unlike α-aminoalkyl and silyl radicals, ligated boryl radicals (LBRs) have not been extensively explored as halogen atom abstractors. In this study, we introduce NHC-ligated boranes as optimal radical chain carriers for the intermolecular reductive radical hydroalkylation and hydroarylation of electron-deficient olefins by using direct UV-A light irradiation. DFT analysis allowed us to rationalize the critical role of the NHC ligand in facilitating efficient chain propagation.

Carbon-doped carbon nitride with improved photocatalytic performance for visible-light-driven Giese reaction

In recent research, there has been significant focus on developing highly efficient photocatalysts for forming C(sp3)-C(sp3) bonds. In this study, a series of carbon-doped carbon nitride (C-CN-x) materials were synthesized through molecular self-assembly and thermal polymerization. The introduction of carbon atoms was found to modulate the band gap, specific surface area, and photoelectric properties of the C-CN-x catalysts. These catalysts were applied in the conjugate addition reaction of 1,3-dioxolane with electron-deficient olefins under blue light irradiation. Among them, C-CN-2 exhibited the highest photocatalytic activity with a yield of 91 %. Remarkably, a comparable yield was achieved under sunlight exposure. Furthermore, a detailed investigation into the reaction mechanism was conducted. This study provided valuable insights into the design and development of highly efficient photocatalysts for C(sp3)-C(sp3) bond formation, with potential applications in organic synthesis and green chemistry.

Cooperative Catalytic Coupling of Benzyl Chlorides and Bromides with Electron-Deficient Alkenes.

Benzyl radicals are an important class of intermediate. The use of visible light to generate them directly from their respective halides is an ideal synthetic strategy. The central impediment associated with their direct single-electron reduction (photo- or electro-) lies in their highly variable and structurally dependent reduction potential, which combine to make the identification of a general set of conditions difficult. Herein, we have employed a strategy of nucleophilic cooperative catalysis in which catalytic lutidine undergoes halide substitution, which decreases and levels the reduction potential. This allows a general set of photocatalytic conditions to transform a broad range of benzyl halides into radicals that can be used in the synthesis of more complex molecules, exemplified here by Giese coupling with electron-deficient alkenes.