Unactivated Alkenes Research Articles

A General Hydrotrifluoromethylation of Unactivated Olefins Enabled by Voltage‐Gated Electrosynthesis

AbstractHere we present the first successful hydrotrifluoromethylation of unactivated olefins under electrochemical conditions. Commercially available trifluoromethyl thianthrenium salt (TT+−CF3BF4−, Ep/2=−0.85 V vs Fc/Fc+) undergoes electrochemical reduction to generate CF3 radicals which add to olefins with exclusive chemoselectivity. The resulting carbon centered radical undergoes a second cathodic reduction, instead of a classical HAT process, to generate a carbanion that can be terminated by protonation from solvent. The use of MgBr2 (+0.20 V onset oxidation potential) plays a key role as an enabling sacrificial reductant for the reaction to operate in an undivided cell. Guided by cyclic voltammetry (CV) studies, fine‐tuning the solvent system, trifluoromethylating reagent's counteranion and careful selection of redox processes, this work led to the development of a voltage‐gated electrosynthesis by pairing two redox processes with a narrow potential difference (ΔE≈1.00 V) allowing the reaction to proceed with two important advances: (a) high reactivity and selectivity towards hydrotrifluoromethylation over undesired dibromination, and (b) an unprecedented functional group tolerance, including aniline, phenols, unprotected alcohol, epoxide, trialkyl amine, and several redox sensitive heterocycles.

Copper‐Catalyzed Simultaneous Dehydrogenation and Enantioselective Allylic Oxidation of Alkanes Using Chiral Heterogeneous Ligands to Produce Allylic Esters and Theoretical Investigation of the Mechanism

ABSTRACTA new asymmetric method for preparing chiral allylic esters from various unactivated alkanes through simultaneous dehydrogenation and enantioselective allylic oxidation in the presence of chiral heterogeneous oxazoline–based ligands is reported for the first time. For this purpose, chiral amino oxazoline ligands, synthesized from chiral amino alcohols and cyanogen bromide, were immobilized on modified MCM‐41 mesoporous silica. These chiral heterogeneous ligands were then characterized using Fourier‐transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, and Brunauer–Emmett–Teller and Barrett–Joyner–Halenda techniques. Finally, copper complexes of these ligands were employed in the synthesis of chiral allylic esters, achieving the best result with a 90% yield and 77% enantiomeric excess. Evaluation of the recyclability of the chiral heterogeneous catalysts revealed that they can be reused three times without a noticeable reduction in the results. In addition, the mechanism of formation of the chiral allylic esters was investigated using a density functional theory method.

Platinum‐Catalyzed Regio‐ and Enantioselective Diboration of Unactivated Alkenes with (pin)B−B(dan)

AbstractAsymmetric diboration of terminal alkenes is well established, and subsequent selective functionalization of the less hindered primary boronic ester is commonly achieved. Conversely, selective functionalization of the sterically less accessible secondary boronic ester remains challenging. An alternative way to control chemoselective functionalization of bis(boron) compounds is by engendering different Lewis acidity to the two boryl moieties, since reactivity would then be dictated by Lewis acidity instead of sterics. We report herein the regio‐ and enantioselective Pt‐catalyzed diboration of unactivated alkenes with (pin)B−B(dan). A broad range of terminal and cyclic alkenes undergo diboration to furnish the differentiable 1,2‐bis(boron) compounds with high levels of regio‐ and enantiocontrol, giving access to a wide variety of novel building blocks from a common intermediate. The reaction places the less Lewis acidic B(dan) group at the less hindered position and the resulting 1,2‐bisboryl alkanes undergo selective transformations of the B(pin) group located at the more hindered position. The regioselectivity of the diboration has been studied by DFT calculations and is believed to originate from the trans influence, which lowers the activation barrier for formation of the regioisomer that places the weaker electron donor [B(pin) vs B(dan)] opposite the strong electron donor (alkyl group) in the platinum complex.

Pd-Catalyzed Selective Defluoroalkylation of Trifluoromethylarenes

The selective functionalization of C–F bonds in trifluoromethylated arenes (ArCF3) is essential due to the extensive use of fluorinated compounds in pharmaceuticals, agrochemicals, and materials science, alongside emerging regulatory restrictions on trifluoromethyl groups. Here, we report a hybrid palladium-catalyzed strategy for the selective defluorination and functionalization of ArCF3, featuring intermolecular carboamination of linear conjugated dienes and defluorinative cross-coupling with unactivated alkenes. This methodology enables the 1,4-addition of dienes with exclusive E-selectivity and the defluoroalkylation of trifluoroarenes, providing an efficient route to difluoromethylated compounds and addressing key challenges in synthetic fluorine chemistry.

Palladium-catalyzed difluoroalkylative carbonylation of unactivated alkenes toward γ-Lactams

Palladium-catalyzed difluoroalkylative carbonylation of unactivated alkenes toward γ-Lactams

Alkyl Sulfonium Salts Enabled Radical Thiocyanohydroxylation of Alkenes.

Herein, we report a novel and practical strategy for alkyl sulfonium salts mediating radical thiocyanohydroxylation of alkenes. This reaction features metal-free and mild conditions, generation of noncarbon radicals from the readily available alkyl sulfonium salts, easy handling, and excellent functional group compatibility. A diverse range of activated and unactivated alkenes worked well to deliver various β-thiocyanato alcohols.

Copper‐Catalyzed Carboamination of Unactivated Alkenes to Synthesize β‐Lactams with Trichloroacetonitrile

ABSTRACTβ‐Lactams, as nitrogen‐containing heterocycles with distinctive biological activities, have made significant contributions to the treatment of infectious diseases. This study which used inexpensive copper salts as catalysts, trichloroacetonitrile as a radical precursor, and potassium carbonate as base offers a concise route for the synthesis of β‐lactam compounds substituted with potentially pharmacologically active dichloroacetyl moieties. Preliminary mechanistic studies indicate that unactivated alkenes undergo sequential intermolecular radical addition and intramolecular amidation reactions. The copper salts undergo catalytic cycles involving Cu(I)/Cu(II)/Cu(III) species.

Remote Migratory Reductive Arylation of Unactivated Alkenes Enabled by Electrochemical Nickel Catalysis.

Transition metal-catalyzed cross-coupling reaction between organometallic reagents and electrophiles is a potent method for constructing C(sp2)-C(sp3) bonds. Given the characters of organometallic reagents, cross-reductive coupling is emerging as an alternative strategy. The resurgence of electrochemistry offers an ideal method for electrochemical reductive of cross-coupling electrophiles. Inspired by the mechanism of electrochemical metal hydride, our study proposed that Ni-H electrochemically catalyze the hydroarylation coupling of unactivated alkenes with aryl halides. 1,1-Diarylalkanes can be produced effectively. This method have advantages including mild conditions, excellent regioselectivity, and satisfactory yields.

Asymmetric Synthesis of Dialkyl Carbinols by Ni-Catalyzed Reductive-Oxidative Relay of Distinct Alkenes.

Enantioenriched unsymmetric dialkyl carbinol derivatives are of importance in natural products, bioactive molecules, and functional organic materials. However, the catalytic asymmetric synthesis of dialkyl carbinol derivatives remains challenging due to the similar steric and electronic properties of two alkyl substituents. Herein, an unprecedented synthesis of chiral dialkyl carbinol ester derivatives from Ni-catalyzed reductive-oxidative relay cross-coupling of two alkenes is developed for the first time. The reaction features the use of enol esters and unactivated alkenes as two different alkyl equivalents to undergo head-to-tail and enantioselective alkyl-alkyl cross-coupling. The reaction undergoes two-electron reduction and single electron oxidation in the presence of both reductants and oxidants. The use of an allyl bromide as single electron acceptor is crucial for the success of this non-trivial asymmetric cross-coupling, providing a new reaction mode for asymmetric alkyl-alkyl bond-forming event in the absence of stoichiometric alkyl electrophiles.

Taming CO2•- via Synergistic Triple Catalysis in Anti-Markovnikov Hydrocarboxylation of Alkenes.

The direct utilization of carbon dioxide as an ideal one-carbon source in value-added chemical synthesis has garnered significant attention from the standpoint of global sustainability. In this regard, the photo/electrochemical reduction of CO2 into useful fuels and chemical feedstocks could offer a great promise for the transition to a carbon-neutral economy. However, challenges in product selectivity continue to limit the practical application of these systems. A robust and general method for the conversion of CO2 to the polarity-reversed carbon dioxide radical anion, a C1 synthon, is critical for the successful valorization of CO2 to selective carboxylation reactions. We demonstrate herein a hydride and hydrogen atom transfer synergy driven general catalytic platform involving CO2•- for highly selective anti-Markovnikov hydrocarboxylation of alkenes via triple photoredox, hydride, and hydrogen atom transfer catalysis. Mechanistic studies suggest that the synergistic operation of the triple catalytic cycle ensures a low-steady-state concentration of CO2•- in the reaction medium. This method using a renewable light energy source is mild, robust, selective, and capable of accommodating a wide range of activated and unactivated alkenes. The highly selective nature of the transformation has been revealed through the synthesis of hydrocarboxylic acids from the substrates bearing a hydrogen atom available for intramolecular 1,n-HAT process as well as diastereoselective synthesis. This technology represents a general strategy for the merger of in situ formate generation with a synergistic photoredox and HAA catalytic cycle to provide CO2•- for selective chemical transformations.

Site Specific C3‐Alkenylation of Indoles Mediated by in situ C‐H Iodination

Text. The C3‐alkenylation of indoles have been developed by means of a novel in situ iodination tactic which is capable of mediating the Heck coupling with alkenes. The method features specific site‐selectivity oriented by the C‐I bond, high‐step efficiency without pre‐functionalization for C‐halogen bond construction, as well as the highly general tolerance to different terminal alkenes, including unactivated alkenes, acrylates, acrylic acid, vinyl sulfone as well as different vinyl functionalized natural products.

Palladium-Catalyzed Site-Selective Hydrogenation of Unactivated Alkenes Directed by 8-Aminoquinoline Amides.

We have developed a method for the site-selective hydrogenation of unactivated alkenes using 8-aminoquinoline amide as the directing group. For unactivated alkenes with two C-C double bonds, Daugulis's 8-aminoquinoline amide facilitated the site-selective hydrogenation of the desired C-C double bond, producing a product in which one C-C double bond was reduced. Site-selective reduction methodologies using intramolecular directing groups are expected to contribute significantly to the synthesis of molecules with multiple reducible functional groups in the future.

Dual Au/Ag Catalyzed Regiospecific Intramolecular Hydroacyloxylation and Hydroalkoxylation of Unactivated Geminal-Substituted Olefins.

A mild, regiospecific Gold-Silver bimetallic catalytic system has been devised for the intramolecular hydroacyloxylation and hydroetherification of alkenoic acids and alcohols. This method exhibits precise specificity for the geminal substituted olefinic center and facilitates the synthesis of substituted phthalide and hydroisocoumarin derivatives. This method has been effectively applied for late-state functionalization to produce bioactive natural products such as rumphellaone A, mycophenolate, and (-)-ambrox. The successful gram-scale synthesis of the anticonvulsant, hypnotic drug (±)-ethyl phenyl butyro lactone (EPBL), (±)-Boivinianin A and the ability to synthesize challenging spiro and bicyclic lactone underscores the synthetic potential of this methodology. Mechanistic insights into gold-silver catalyzed lactonization of olefins have also been discussed.

Alkylcyanation of Unactivated Alkenes with Protic C(sp3)‐H Feedstocks via Radical‐Initiated Intramolecular Cyano Group Migration Enabled by Photoredox/Brønsted Base Dual Catalysis

Cyanofunctionalization of alkenes via radical‐initiated cyano migration was a straightforward pathway to access alkyl nitriles. Herein, By the synergistic merger of photoredox catalysis and Brønsted base catalysis, a mild protocol of alkylcyanation of unactivated alkenes with protic C(sp3)−H feedstocks via intramolecular 1,4‐cyano group migration was reported. This method was enabled in an atom‐, and step‐economy manner, delivering a series of γ‐cyanoester derivatives in moderate to excellent yields.

Cyano-Fluorosulfonylation of Unactivated Alkenes by Photoredox and Copper Dual Catalysis.

Both fluorosulfonyl and cyano groups are important structural motifs in bioactive molecules. Herein, we report a new difunctionalization reaction of alkenes based on fluorosulfonyl radicals, which allows for the introduction of the fluorosulfonyl and cyano groups into unactivated alkenes in one step. This transformation is enabled by merging photoredox and copper catalysis, featuring visible light catalysis, mild conditions, and good functional group tolerance. Further transformation of products via SuFEx reactions is also demonstrated.

Triphasic Hydroxysilylation of Alkenes by Mechanically Piezoelectric Catalysis

AbstractThe 1,2‐hydroxysilylation of alkenes is crucial for synthesizing organosilicon compounds which are key intermediates in material science, pharmaceuticals, and organic synthesis. The development of strategies employing hydrogen atom transfer pathways is currently hindered by the existence of various competing reactions. Herein, we reported a novel mechanochemical strategy for the triphasic 1,2‐hydroxysilylation of alkenes through a single‐electron‐transfer pathway. Our approach not only circumvents competitive reactions to enable the first‐ever 1,2‐hydroxysilylation of unactivated alkenes but also pioneers the research in mechanic force‐induced triphasic reactions under ambient conditions. This gentle method offers excellent compatibility with various functional groups, operates under simple and solvent‐free conditions, ensures rapid reaction time. Preliminary mechanistic investigations suggest that silylboronate can be transformed to a silicon radical by highly polarized Li2TiO3 particles and oxygen under ball‐milling condition.

Bicyclo[2.1.1]hexanes via Intramolecular Formal (3+2)‐Cycloaddition

We report a synthesis of bicyclo[2.1.1]hexanes via an intramolecular formal (3+2) cycloaddition of allylated cyclopropanes bearing a 4‐nitrobenzimine substituent. Both activated and unactivated alkenes are tolerated in the transformation. The bicyclic imine products are prone to photo‐induced ring opening, allowing for the epimerization of C5‐stereogenic compounds.

Bicyclo[2.1.1]hexanes via Intramolecular Formal (3+2)-Cycloaddition.

We report a synthesis of bicyclo[2.1.1]hexanes via an intramolecular formal (3+2) cycloaddition of allylated cyclopropanes bearing a 4-nitrobenzimine substituent. Both activated and unactivated alkenes are tolerated in the transformation. The bicyclic imine products are prone to photo-induced ring opening, allowing for the epimerization of C5-stereogenic compounds.

Study of Palladium-Catalyzed Site and Regioselective Reductive Heck Hydroarylation of Unactivated Alkene.

We studied the reaction pathway of our reductive Heck hydroarylation using a palladium catalyst and a hydrosilane. A key question to verify the reaction mechanism was which active species, Ar-PdII-I or Si-PdII-H, first performs migratory insertion into the alkenes. Identifying this step is crucial to elucidate the reaction mechanism. To address this, we designed a substrate containing two trisubstituted alkenes and tested its product. The results suggest that the migratory insertion of Ar-PdII-I into the alkene is the initial step of the reaction. Furthermore, this reaction can construct a quaternary carbon center and give high yields with high functional group tolerance.

Regiodivergent Radical-Relay Alkene Dicarbofunctionalization.

Herein, we report a regiodivergent 1,n-dicarbofunctionalization of unactivated olefins enabled by a Ni-catalyzed radical relay that forges both C(sp3)-C(sp3) and C(sp2)-C(sp3) linkages, even at long-range. Initial studies support an intertwined scenario resulting from the merger of an atom-transfer radical addition (ATRA) and a chain-walking event, with site-selectivity being dictated by a judicious choice of the ligand backbone.