Hydroarylation Products Research Articles

Dearomative Cyclization/Spirocyclization via Electrochemical Reductive Hydroarylation of Nonactivated Arenes.

An electrochemical cyclization/spirocyclization hydroarylation via reductive dearomatization of a series of nonactivated arenes including N-substituted indoles, indole-3-carboxamide derivatives, and iodo-substituted benzamides is described. This protocol boasts high atom efficiency, broad substrate applicability, and excellent selectivity. Utilizing a simple undivided cell, various nonactivated arenes undergo cyclization/spirocyclization through the intramolecular addition of aryl radicals to an aromatic ring, yielding 50 indolines, spirocyclizative hydroarylation products, and phenanthridinones.

Synthesis of Benzo[a]carbazoles and Dibenzo[c,g]carbazoles via Sequential Gold Catalysis and Photomediated Cyclization.

Herein, we report a reaction protocol for the construction of benzo[a]carbazole and dibenzo[c,g]carbazole frameworks. The detailed gold catalytic reaction conditions developed for the challenging intermolecular carbon nucleophilic addition to internal alkynes are realized, giving the desired alkyne hydroarylation products in good yields. The resulting trisubstituted alkenes are able to undergo photomediated cyclization, furnishing the desired carbazole molecules with excellent yields and high efficiency.

Nickel(II)/Lewis acid catalysed olefin hydroamination and hydroarylation under mild conditions.

Aniline derivatives are important nitrogen-containing compounds with wide applications in chemicals, pharmaceuticals and agrochemicals. In the work described herein, nickel(II)/Lewis acid (LA) catalysed olefin hydroamination with anilines was explored for use in aniline derivative syntheses. The Ni(II)/LA catalysis proceeded smoothly under mild conditions, whereas using Ni(OAc)2 alone, the catalyst was inactive. Remarkably, the Markovnikov addition type products were obtained when substituted styrenes were used as the olefin source, while the anti-Markovnikov addition type products were obtained when the electron-deficient olefins such as acrylonitrile and acrylates were used. The mechanistic studies revealed that hydroamination of the styrene derivates proceeded via the amino-Ni(II)/LA attacking the carbocation intermediate which was generated by the protonation of the olefin, whereas for acrylonitrile and acrylates, it proceeded by a direct amino-Ni(II)/LA attack on the olefin by nucleophilic addition. In addition, the hydroarylation product was generated by the Hofmann-Martius rearrangement of the hydroamination product.

Aluminium trichloride-promoted tandem hydroarylation–ionic hydrogenation of 3-arylpropynoic acid derivatives and 4-phenylbut-3-yn-2-one

Reactions of 3-arylpropynoic acid derivatives and conjugated acetylene ketones with arenes and cyclohexane under the action of AlCl3 at room temperature for 15 h afford the corresponding products of one-pot tandem hydroarylation–ionic hydrogenation of the acetylene bond of the starting compounds in 42–98% yields. This reaction is accompanied by aryl group exchange process under acidic conditions.

Divergent Coupling of ortho-Alkynylnaphthols and Benzofurans: [4 + 2] Cycloaddition and Friedel-Crafts Reaction.

Catalytic direct [4 + 2] cycloaddition reactions and Friedel-Crafts reactions of ortho-alkynylnaphthols with benzofurans have been developed, affording functionalized hydrobenzofuro[3,2-b]chromans and hydroarylation products, respectively, in high yields with high chemoselectivity.

Synthesis of 3-Aryl-3-(Furan-2-yl)Propanoic Acid Derivatives, and Study of Their Antimicrobial Activity.

Reactions of 3-(furan-2-yl)propenoic acids and their esters with arenes in Brønsted superacid TfOH affords products of hydroarylation of the carbon–carbon double bond, 3-aryl-3-(furan-2-yl)propenoic acid derivatives. According to NMR and DFT studies, the corresponding O,C-diprotonated forms of the starting furan acids and esters should be reactive electrophilic species in these transformations. Starting compounds and their hydroarylation products, at a concentration of 64 µg/mL, demonstrate good antimicrobial activity against yeast-like fungi Candida albicans. Apart from that, these compounds suppress Escherichia coli and Staphylococcus aureus.

Heterogeneously-catalyzed competitive hydroarylation/hydromination of norbornene with aniline in the presence of Aquivion® ionomer

The hydroarylation of alkenes with aniline is a reaction of high interest, in particular for the manufacture of polyurethanes. This reaction has been mostly investigated in the presence of homogeneous catalysts. So far, heterogeneous catalysts have been scarcely reported for this reaction, mainly due to their inherent low activity and deactivation during the course of the reaction. Here we report the catalytic performance of Aquivion® ionomer, a perfluorinated solid acid polymer, in the hydroarylation of norbornene with aniline. We show that Aquivion® ionomer was robust and can be recycled for at least 6 runs without any decrease of its catalytic performances. Our results also highlight that Aquivion® ionomer improves the propensity of aniline to react through its aromatic ring, thus yielding a higher proportion of hydroarylation products as compared to other tested homogeneous and heterogeneous catalysts.

Metal-free intramolecular hydroarylation of alkynes

An efficient metal-free intramolecular hydroarylation reaction of alkynes is described here. A series of aryl andN-group attached alkynes generated the intramolecular hydroarylation products in high yields.

Environmentally Friendly Cp*Co(III)-catalyzed C-H Bond Hydroarylation of Alkynes

A facile synthetic method of Alkenylarene derivatives via cobalt(III)-catalyzed C-H hydroarylation with terminal alkynes has been presented. This helpful protocol provides a way to use terminal alkynes to couple with aryl groups through 1, 2-insertion, with high yield and good selectivity to obtain the corresponding hydroarylation products.

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions.

Acetylene derivatives of 1,2,4-oxadiazoles, i.e., 5-(2-arylethynyl)-3-aryl-1,2,4-oxadiazoles, have been obtained, for the first time reported, from 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles by their bromination at the carbon–carbon double bond followed by di-dehydrobromination with NaNH2 in liquid NH3. The reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed.

Nickel-Catalyzed Regiodivergent Reductive Hydroarylation of Styrenes

AbstractWe report a ligand-controlled nickel-catalyzed reductive hydroarylation of styrenes with predictable and controllable regioselectivity. With a diamine ligand, the reaction produces selective linear hydroarylation products. Alternatively, with a chiral PyrOx ligand, branch-selective enantioenriched 1,1-diarylalkane products are obtained. Preliminary mechanistic results are consistent with a reductive Heck process.

Triflic Acid Promoted Transformations of Linear‐Conjugated Enynones and their Reactions with Arenes. Synthesis of Dihydropyranones, Conjugated Dienones, and Indanes

AbstractLinear‐conjugated enynones,1,5‐diarylpent‐4‐en‐2‐yn‐1‐ones [Ar2−CH=CH−C≡C−C(=O)Ar1], have been cyclized into 2,6‐diaryl‐2,3‐dihydropyran‐4‐ones in triflic acid TfOH (CF3SO3H). Reactions of these enynones with arenes Ar3H in TfOH have afforded, at first stage, products of hydroarylation of the acetylene bond, 1,3,5‐triarylpent‐2,4‐dien‐1‐ones [Ar2−CH=CH−C(Ar3)=CH−C(=O)Ar1], which have been further cyclized into alkylidene indanes. Plausible reaction mechanisms have been proposed. According to quantum chemical calculations by DFT method, initial key reactive intermediates are vinyl type dications [Ar2−CH=CH−C+=CH−C(=O+H)Ar1], generated under the protonation of carbonyl oxygen and acetylene bond of starting enynones in TfOH.

BH3 ⋅ Me2S: An Alternative Hydride Source for NiH‐Catalyzed Reductive Migratory Hydroarylation and Hydroalkenylation of Alkenes

AbstractBorane dimethylsulfide (BMS) was found to be an efficient hydride source for nickel‐hydride catalyzed reductive migratory hydrofunctionalization reactions. Catalytic reductive migratory hydroarylation and migratory hydroalkenylation were achieved with BMS in high yields and with excellent regioselectivity. A large‐scale experiment employing as little as 0.5 equivalents of BH3 ⋅ Me2S as the hydride source delivered the desired migratory hydroarylation product in high yield and selectivity.

Theoretical mechanistic study of nickel‐catalyzed anti‐Markovnikov hydroarylation of alkenes

AbstractTransition metal‐catalyzed hydroarylation of alkenes can provide various Markovnikov products, but so‐called anti‐Markovnikov additions to alkenes are rarely reported. Here, a divalent nickel hydride complex catalyzed anti‐Markovnikov reductive cross‐coupling of styrene and aryl iodide has been investigated using density functional theory. The reaction occurs via the regio‐determining hydronickelation, the oxidative addition of the CI bond to Ni(II) center, and the rate‐determining reductive elimination of hydroarylation product. The electronic processes were investigated with a fragment molecular orbital analysis to understand the origin of anti‐Markovnikov selectivity and successive oxidative addition and reductive elimination steps.

Zeolite catalyzed hydroarylation of alkenes with aromatic amines under organic ligand-free conditions

The hydroarylation of alkenes with aromatic amines is recognized as the most atom-economical and straightforward approach to obtain functional aromatic amines, which are versatile building blocks in organic synthesis and material chemistry. However, controllable synthesis of single hydroarylation product is still a significant challenge because hydroarylation reaction often delivers four hydroarylation products and hydroamination products are also produced during the reaction. Herein, we report the first example of heterogeneous zeolite catalyzed hydroarylation of styrene and norbornene with aniline derivatives under organic ligand-free conditions. With the USY zeolite as catalyst, a wide scope of alkenes and aromatic amines with various functional groups are smoothly converted into the corresponding products in 48–95% yields with high regioselectivity. Detailed characterizations revealed that Lewis acid can promote Hofmann-Martius rearrangement of hydroamination products toward hydroarylation products, resulting in high selectivity for hydroarylation products. In addition, it could be found that the weak acid sites of zeolite play a key role in forming hydroarylation products. Furthermore, the catalyst can be reused at least 10 times without obvious deactivation. This work may promote the development of heterogeneous catalyst system for alkene hydroarylation.

Reactions of 3-arylpropenenitriles with arenes under superelectrophilic activation conditions: Hydroarylation of the carbon-carbon double bond followed by cyclization into 3-arylindanones

Reactions of 3-arylpropenenitriles [ArCHCHCN] with arenes [Ar’H] under the superelectrophilic activation conditions with Brønsted superacid TfOH (CF3SO3H) or strong Lewis acid AlBr3 result, first, in the formation of products of hydroarylation of the carbon-carbon double bond, 3,3-diarylpropanenitriles [Ar(Ar’)CHCH2CN]. Reactions may go further in TfOH leading to 3-arylindanones, as products of intramolecular aromatic acylation by the electrophilically activated nitrile group. Intermediate cationic species, derived at the protonation of the starting 3-arylpropenenitriles onto the carbon of CC bond and the nitrile nitrogen, have been studied by DFT calculation. A plausible reaction mechanism including the formation of highly reactive dications [(Ar)HC+–CH2C+ = NH] has been proposed. The obtained 3,3-diarylpropanenitriles have been transformed into pharmaceutically valuable 5-(2,2-diarylethyl)-1H-tetrazoles [Ar(Ar’)CHCH2Tetr] and 3-diarylpropylamines [Ar(Ar’)CH(CH2)2NH2] by the reactions with NaN3 and LiAlH4 correspondingly.

Directing-Group-Controlled Ring-Opening Addition and Hydroarylation of Oxa/azabenzonorbornadienes with Arenes via C-H Activation.

An efficient method for the directing group controlled rhodium-catalyzed addition reaction of oxa/azabicylic alkenes with aromatic ketones and benzoic acids has been developed. The ketones and benzoic acids afforded different addition products when reacted with oxa/azabicyclic alkenes. The reaction between ketones and azabenzonorbornadienes furnished the ring-opening addition products. The reaction between benzoic acids and aza/oxabicyclic alkenes proceeded in the absence of silver salt, giving the 1:2 hydroarylation products in yields up to 96%.

Nickel-Catalyzed Hydroarylation of in Situ Generated 1,3-Dienes with Arylboronic Acids Using a Secondary Homoallyl Carbonate as a Surrogate for the 1,3-Diene and Hydride Source.

The nickel-catalyzed hydroarylation of 1,3-dienes with arylboronic acids using a secondary homoallyl carbonate as a surrogate for the 1,3-diene and hydride source has been developed. The synthetic strategy allowed an efficient access to a wide array of hydroarylation products in high yields with high functional group compatibility without the use of an external hydride source. Mechanistic experiments indicated that the alkene-directed oxidative addition and subsequent β-hydride elimination would be a critical process in this transformation.

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates.

3-Methylbuta-1,2-dien-1-ylphosphonic acid derivatives (phosphorylallenes) [X2(O=)P–CR=C=CMe2, X = Cl, OMe, NR2, or SAr] undergo intramolecular cyclization into the corresponding 1,2-oxaphospholium ions in the Brønsted superacid TfOH. These cations have been thoroughly studied by means of NMR spectroscopy. The hydrolysis of superacidic solutions of these species afforded cyclic phosphonic acids and other phosphorus-containing compounds. Contrary to Brønsted acids, 3-methylbuta-1,2-dien-1-ylphosphonic dichloride [Cl2(O=)P–HC=C=CMe2] reacted with the Lewis acid AlCl3 in an intermolecular way forming noncyclic intermediates, which were investigated by NMR spectroscopy and DFT calculations. Hydrolysis of these species resulted in the formation of phosphoryl-substituted allyl alcohols and 1,3-butadienes. A strong coordination of the oxygen of the P=O group with AlCl3 prevented the formation of cyclic 1,2-oxaphospholium ions and played a crucial role in the different reactivity of such phosphorylallenes under the action of Brønsted or Lewis acids. Apart from that, the reaction of dichlorophosphorylallenes with arenes and AlCl3 led to products of hydroarylation of the allene system, phosphoryl-substituted alkenes and/or indanes. This is the first example of a Lewis acid-promoted intermolecular hydroarylation of allenes bearing electron-withdrawing substituents. Plausible reaction mechanisms have been proposed on the basis of the investigated reactions, and NMR analysis and DFT studies of the intermediate cationic species.

Mechanistic Study of Manganese-Catalyzed C-H Bond Functionalizations: Factors Controlling the Competition between Hydroarylation and Cyclization.

The Mn-catalyzed C-H functionalization of indoles with allenes developed by Rueping and co-workers provides an efficient access to various alkenylated indoles and substituted pyrroloindolones. Herein, we present a systematic computational study to understand the mechanism and origins of substrate-controlled chemoselectivity of the C-H functionalization reactions (hydroarylation vs cascade cyclization). For the disubstituted allene system, the computed mechanism consists of three main phases: C-H activation, allene migratory insertion, and protonation giving the hydroarylation product. All of these steps are feasible, in agreement with the good yield under the mild experimental conditions. On the other hand, for the trisubstituted allene system, hydroarylation is suppressed due to the higher energy barrier for the protonation step arising from the disfavored ligand-substrate steric repulsions between the carboxide ligand and the substituent group in the allene substrate; our computational results demonstrate that, after the allene insertion leading to a seven-membered cyclometalated intermediate, it undergoes a reaction pathway involving sequential "ketone to enol" isomerization, a 1,4-heteroaryl shift, and β-methoxyl elimination giving the pyrroloindolone product. In contrast, this isomerization → heteroaryl shift → β-methoxyl elimination process is unworkable in the disubstituted allene system, because the protonation step takes place more favorably owing to the lack of ligand-substrate steric interactions. The findings taken together give an insight into the role of the ligand-substrate interactions in directing the competitive pathways and differentiating the energies of key transition states by steric repulsions.