Electrochemical Intramolecular Aminooxygenation of Unactivated Alkenes

An electrochemical approach to the intramolecular aminooxygenation of unactivated alkenes has been developed. This process is based on the addition of nitrogen‐centered radicals, generated through electrochemical oxidation, to alkenes followed by trapping of the cyclized radical intermediate with 2,2,6,6‐tetramethylpiperidine‐N‐oxyl radical (TEMPO). Difunctionalization of a variety of alkenes with easily available carbamates/amides and TEMPO affords aminooxygenation products in high yields and with excellent trans selectivity for cyclic systems (d.r. up to>20:1). The approach provides a much‐needed complementary route to existing cis‐selective methods.     

Iron‐Catalyzed Ring‐Closing C−O/C−O Metathesis of Aliphatic Ethers

Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring‐closing reactions. Herein, we report an iron‐catalyzed ring‐closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.     

Radical Heteroarylalkylation of Alkenes via Three‐Component Docking‐Migration Thioetherification Cascade

A novel, rational‐designed approach to access various heteroaryl‐substituted alkyl thioethers was developed via docking‐migration cascade process. By utilizing three components involving alkene, dual‐function reagent, and thioetherificating reagent, radical heteroarylalkylation of alkenes followed by thiolation of the alkyl radical intermediates proceeded smoothly, manifesting well compatibility of substrates and cascade transformations. Furthermore, this protocol also features mild conditions, broad substrate scope, and wide product diversity.     

Copper‐Catalyzed Oxyboration of Unactivated Alkenes

The first regiodivergent oxyboration of unactivated terminal alkenes is reported, using copper alkoxide as a catalyst, bis(pinacolato)diboron [(Bpin)₂] as a boron source, and (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) as an oxygen source. The reaction is compatible with various functional groups. Two regioisomers are selectively produced by selecting the appropriate ligands on copper. The products may be used as a linchpin precursor for various other functionalizations, and net processes such as carbooxygenation, aminooxygenation, and dioxygenation of alkenes can be achieved after C?B bond transformations. Mechanistic studies indicate that the reaction involves the following steps: 1) Transmetalation between CuOtBu and (Bpin)₂ to generate a borylcopper species; 2) regiodivergent borylcupration of alkenes; 3) oxidation of the thus‐generated C?Cu bond to give an alkyl radical; 4) trapping of the resulting alkyl radical by TEMPO.     

Enantioselective Synthesis of Chiral Isotopomers of 1‐Alkanols by a ZACA–Cu‐Catalyzed Cross‐Coupling Protocol

Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non‐measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1‐alkanols, with ≥99 % enantiomeric excess (ee), by the Zr‐catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu‐catalyzed cross‐coupling reactions. ZACA‐in situ iodinolysis of allyl alcohol and ZACA‐in situ oxidation of TBS‐protected ω‐alkene‐1‐ols protocols were applied to the synthesis of both (R)‐ and (S)‐difunctional intermediates with 80–90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase‐catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1‐alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium‐labeled groups by Cu‐catalyzed cross‐coupling reactions without epimerization.     

Cooperative Catalysis of Noncompatible Catalysts through Compartmentalization: Wacker Oxidation and Enzymatic Reduction in a One‐Pot Process in Aqueous Media

A Wacker oxidation using CuCl/PdCl₂ as a catalyst system was successfully combined with an enzymatic ketone reduction to convert styrene enantioselectively into 1‐phenylethanol in a one‐pot process, although the two reactions conducted in aqueous media are not compatible due to enzyme deactivation by Cu ions. The one‐pot feasibility was achieved via compartmentalization of the reactions. Conducting the Wacker oxidation in the interior of a polydimethylsiloxane thimble enables diffusion of only the organic substrate and product into the exterior where the biotransformation takes place. Thus, the Cu ions detrimental to the enzyme are withheld from the reaction media of the biotransformation. In this one‐pot process, which formally corresponds to an asymmetric hydration of alkenes, a range of 1‐arylethanols were formed with high conversions and 98–99 % ee. In addition, the catalyst system of the Wacker oxidation was recycled 15 times without significant decrease in conversion.     

Sulfinate and Carbene Co‐catalyzed Rauhut–Currier Reaction for Enantioselective Access to Azepino[1,2‐a]indoles

A carbene and sulfinate co‐catalyzed intermolecular Rauhut–Currier reaction between enals and nitrovinyl indoles is disclosed. The carbene catalyst activates the enal and the sulfinate co‐catalyst activates the nitrovinyl indole. Both activation processes are realized via the formation of covalent bonds between the catalysts and substrates to generate catalyst‐bound intermediates. The dual catalytic reaction affords azepino[1,2‐a]indole products with excellent stereoselectivity. Our study demonstrates the unique involvement of sulfinate as an effective nucleophilic catalyst in activating electron‐deficient alkenes for asymmetric reactions. This dual catalytic approach should also encourage future explorations of both sulfinate and carbene catalysts for new reactions.     

Electrochemical Oxidative [4+2] Annulation for the π‐Extension of Unfunctionalized Heterobiaryl Compounds

Considering their unique electronic properties and diverse biological activities, regioselective access to fused aromatic compounds is significantly important in the field of organic materials and pharmaceutical science. Herein, we developed electrochemical oxidative [4+2] annulation reactions of heterobiaryl compounds with alkynes or alkenes, leading to the formation of several polycyclic heteroaromatic compounds. This electrosynthetic methodology serves for the straightforward π‐extension of unfunctionalized heterobiaryl compounds. The requirements of additional oxidants and prefunctionalization of starting materials are obviated. Through the in situ generation of heterobiaryl radical cation intermediates, various fused aromatic compounds were obtained with good yields and excellent regioselectivity.     

Electrochemical Oxidative [4+2] Annulation for the π-Extension of Unfunctionalized Heterobiaryl Compounds

Considering their unique electronic properties and diverse biological activities, regioselective access to fused aromatic compounds is significantly important in the field of organic materials and pharmaceutical science. Herein, we developed electrochemical oxidative [4+2] annulation reactions of heterobiaryl compounds with alkynes or alkenes, leading to the formation of several polycyclic heteroaromatic compounds. This electrosynthetic methodology serves for the straightforward π-extension of unfunctionalized heterobiaryl compounds. The requirements of additional oxidants and prefunctionalization of starting materials are obviated. Through the in situ generation of heterobiaryl radical cation intermediates, various fused aromatic compounds were obtained with good yields and excellent regioselectivity.     

Generation of Aromatic N-Heterocyclic Radicals for Functionalization of Unactivated Alkenes

Nitrogen-centered radicals (NCRs) have been widely recognized as versatile synthetic intermediates for the construction of nitrogen containing molecules of high value. As such, there has been a long-standing interest in the field of organic synthesis to develop novel nitrogen-based radicals and explore their inherent reactivity. In this study, we present the generation of aromatic N-heterocyclic radicals and their application in a novel and diverse functionalization of unactivated alkenes. Bench-stable aromatic N-heterocyclic pyridinium salts were employed as crucial NCR precursors, which enabled the efficient conversion of various unactivated alkenes into medicinally relevant alkylated N-heterocyclic amines. This approach offers an unexplored retrosynthetic disconnection for the synthesis of related molecules that commonly possess therapeutic value. Furthermore, this platform can be extended to the synthesis of densely functionalized heterocyclic amines by utilizing disulfides and diethyl bromomalonate as radical quenchers. Mechanistic investigations indicate an energy transfer (EnT) pathway involving the formation of a transient aromatic N-heterocyclic radical, radical addition to unactivated alkenes, and subsequent generation of the amination product through either hydrogen atom transfer (HAT) or radical addition processes.     

Photochemical and Electrochemical Carbon Dioxide Utilization with Organic Compounds

In the last few years, photochemical and electrochemical CO₂ transformations have attracted increasing attention in response to topical interest in renewable energy and green chemistry. The present minireview offers an overview about the current approaches for the photochemical and electrochemical carbon dioxide fixation with organic compounds. Valuable products, including carboxylic acids and heterocyclic compounds, are accessible through carboxylation and carboxylative cyclization, respectively. In photochemical and electrochemical processes, photo‐ or electro‐induced radical ions or other high‐energy organic compounds are considered as key intermediates to react with CO₂. Besides, activation of CO₂ to produce radical anion has also been reported.     

CuPd Nanoparticles as a Robust Catalyst for Electrochemical Allylic Alkylation

An efficient CuPd nanoparticle (NP) catalyst (3 nm CuPd NPs deposited on carbon support) is designed for catalyzing electrochemical allylic alkylation in water/isopropanol (1:1 v/v) and 0.2 m KHCO₃ solution at room temperature. The Pd catalysis was Pd/Cu composition‐dependent, and CuPd NPs with a Pd/Cu ratio close to one are the most efficient catalyst for the selective cross‐coupling of alkyl halides and allylic halides to form C?C hydrocarbons with product yields reaching up to 99 %. This NP‐catalyzed electrochemical allylic alkylation expands the synthetic scope of cross‐coupling reactions and can be further extended to other organic reaction systems for developing green chemistry electrosynthesis methods.     

Copper-Catalyzed Chemo- and Enantioselective Radical 1,2-Carbophosphonylation of Styrenes

The copper-catalyzed enantioselective radical difunctionalization of alkenes from readily available alkyl halides and organophosphorus reagents possessing a P−H bond provides an appealing approach for the synthesis of α-chiral alkyl phosphorus compounds. The major challenge arises from the easy generation of a P-centered radical from the P−H-type reagent and its facile addition to the terminal side of alkenes, leading to reverse chemoselectivity. We herein disclose a radical 1,2-carbophosphonylation of styrenes in a highly chemo- and enantioselective manner. The key to the success lies in not only the implementation of dialkyl phosphites with a strong bond dissociation energy to promote the desired chemoselectivity but also the utilization of an anionic chiral N,N,N-ligand to forge the chiral C(sp³)−P bond. The developed Cu/N,N,N-ligand catalyst has enriched our library of single-electron transfer catalysts in the enantioselective radical transformations.     

The Catalytic Effect of Polypyrrole/Pt‐Cu on Oxygen Reduction Reaction

This paper studies the electrochemical properties of ppy/Pt‐Cu composite for oxygen reduction reaction (ORR) and compares it to the highly porous ppy/Pt‐Cu catalyst, which can be synthesized by galvanostatic method (ppy/Pt‐Cu(GS)). The results of the polarization, rotating disk electrode and electrochemical impedance tests are discussed to determine the electrochemical properties of the catalysts. According to the results, ppy/Pt‐Cu(GS) catalyst is more active toward ORR compared to ppy/Pt‐Cu catalyst. The rotating disk electrode data indicates four‐electron transfer mechanism for this catalyst.     

Radical additions of xenon difluoride to cis- and trans-1-phenylpropenes: comparison with trichloramine and iodobenzene dichloride

We would like to report data which support a free radical pathway for reaction of xenon difluoride (XeF₂) with alkenes in organic solvent. Radical intermediates have been proposed for reaction of XeF₂ to double bonds. For example, a radical pathway was suggested for the gas phase reaction of XeF₂ to ethylene and propene [1]. Zupan speculated on a radical cation pathway for the acid catalyzed reaction of XeF₂ with alkenes but gave no experimental evidence for this mechanism [2,3]. Radical cation intermediates were demonstrated for the reaction of XeF₂ to aromatics by Filler [4]. Acid catalyzed ionic reactions to unsaturated hydrocarbons have been reviewed [5].Zupan and Pollak have shown that alkenes do not react in aprotic solvent with XeF₂ at low concentrations of alkene unless acid catalyst is present [3]. However, we observed that illumination of a dilute solution of $\text{cis-}$ or $\text{trans}$-1-phenylpropenes (I) or (II) in methylene chloride at 0° with a 270 watt sunlamp produced IIIa and IIIb in less then two hours (Table). Furthermore, at high concentration of (I) and (II), a spontaneous reaction occurred in the dark between XeF₂ and these styrenes. The reaction conditions for both of these reactions imply a radical mechanism — the latter a molecule-induced pathway.     

Transition-Metal-Free Three-Component Radical 1,2-Amidoalkynylation of Unactivated Alkenes

A transition-metal-free radical 1,2-amidoalkynylation of unactivated alkenes is presented. α-Amido-oxy acids were used as amidyl radical precursors, which were oxidized by an organic photoredox catalyst (4CzlPN). The electrophilic N-radicals chemoselectively reacted with various aliphatic alkenes and the adduct radicals were then trapped by ethynylbenziodoxolone (EBX) reagents to eventually provide the amidoalkynylation products. These transformations, which were conducted under practical and mild conditions, showed high functional group tolerance and broad substrate scope. Mechanistic studies supported the radical nature of these cascades.     

Copper‐Catalyzed Carbotrifluoromethylation of Unactivated Alkenes Driven by Trifluoromethylation of Alkyl Radicals

We report herein an unprecedented protocol for radical carbotrifluoromethylation of unactivated alkenes. With Cu(OTf)₂ as the catalyst, the reaction of unactivated alkenes, TMSCF₃ and activated alkyl chlorides at room temperature provides the corresponding carbotrifluoromethylation products in satisfactory yields. Directed by trifluoromethylation of alkyl radicals, the method exhibits an excellent regioselectivity that is opposite to those driven by CF₃ radical addition.     

Copper-catalyzed iminohalogenation of γ, δ-unsaturated oxime esters with halide salts: Synthesis of 2-halomethyl pyrrolines

A copper-catalyzed iminohalogenation of unactivated alkenes of γ, δ-unsaturated oxime esters is achieved by using readily available halide salts. Utilizing this protocol, a sequence of structurally diversiform 2-halomethyl pyrrolines are efficiently synthesized and a mechanism involving iminyl radical intermediates, which were initiated by Cu(I) species, was proposed.     

The mechanism of the addition of haloalkanes to alkenes in the presence of dichlorotris(triphenylphosphine)ruthenium(II), [RuCl2(PPh3)3]

The addition of haloalkanes to alkenes in the presence of [RuCl₂(PPh₃)₃] has been subjected to a detailed kinetic study. The results of this study, together with an examination of reaction intermediates, suggest a mechanism inolving a non-chain sequence in which [RuCl₂(PPh₃)₃] acts as a catalyst, but which involves free radical intermediates.     

Chloroacetate‐Promoted Selective Oxidation of Heterobenzylic Methylenes under Copper Catalysis

The efficient selective oxidation and functionalization of C? H bonds with molecular oxygen and a copper catalyst to prepare the corresponding ketones was achieved with ethyl chloroacetate as a promoter. In this transformation, various substituted N‐heterocyclic compounds were well tolerated. Preliminary mechanistic investigations indicated that organic radical species were involved in the overall process. The N‐heterocyclic compounds and ethyl chloroacetate work synergistically to activate C? H bonds in the methylene group, which results in the easy generation of free radical intermediates, thus leading to the corresponding ketones in good yields.