Hydroarylation Of Alkenes Research Articles

Synthesis of Indole-Fused Polycyclics via Rhodium-Catalyzed Undirected C-H Activation/Alkene Insertion.

A Rh(III)-catalyzed undirected C-H activation/alkene insertion to synthesize diversified indole-fused polycyclics has been developed. Intramolecular electrophilic cyclization generated a 3-indolyl rhodium species that went through an aryl-to-aryl 1,4-rhodium migration to realize the C-H activation. The subsequent [4 + 2] carboannulation or hydroarylation of alkenes could be achieved, respectively, by simply adjusting the additives of the reaction.

Olefin Hydroarylation via Ni/Co Dual Catalysis

Cobalt/nickel dual-catalysis enables the branch-selective hydroarylation of olefins through a novel "cage-rebound" transmetalation pathway. This process allows for the rapid introduction of complexity by coupling readily available iodoarenes with abundant and unbiased alkenes without the need for substrate prefunctionalization.

Hydroarylation of Alkynes and Alkenes Catalyzed by Alumina-Sulfuric Acid

Hydroarylation of Alkynes and Alkenes Catalyzed by Alumina-Sulfuric Acid

Rhodium(III)-Catalyzed Intramolecular Olefin Hydroarylation of Aromatic Aldehydes Using a Transient Directing Group.

A Rh(III)-catalyzed intramolecular olefin hydroarylation of aromatic aldehydes with a transient directing group has been described. The bidentate directing groups in situ generated from aromatic aldehydes and β-alanine could enable the subsequent C-H activation and hydroarylation with excellent site selectivities and high functional group compatibility. The further conversion of the aldehyde group showcased the broad application prospects of this methodology.

Hydroarylation of alkynes and alkenes through alumina-sulfuric acid catalyzed regioselective C[sbnd]C bond formation

A highly atom-efficient synthetic protocol for hydroarylation of terminal-aryl alkynes and styrene through the regioselective CC bond formation via the electrophilic addition of naphthols and substituted phenols has been developed using alumina-sulfuric acid as a heterogeneous supported solid acid catalyst. This methodology shows excellent regioselectivity and affords the desired product in good to excellent yield. The heterogeneous catalyst can also be recycled efficiently without much loss of activity.

Nickel-catalyzed anti-Markovnikov hydroarylation of alkenes.

We have developed a nickel-catalyzed hydroarylation of alkenes using aryl halides as coupling partners. Excellent anti-Markovnikov selectivity is achieved with aryl-substituted alkenes and enol ethers. We also show that hydroarylation occurs with alkyl substituted alkenes to yield linear products. Preliminary examination of the reaction mechanism suggests irreversible hydrometallation as the selectivity determining step of the hydroarylation.

Influence of N-Heterocyclic Carbene Steric Bulk on Selectivity in Nickel Catalyzed C–H Bond Silylation, Germylation, and Stannylation

A series of Ni(0) compounds supported by electronically similar N-heterocyclic carbene (NHC) ancillary ligands with a range of %Vbur were used as catalysts for aryl C–H bond silylation, germylation, and stannylation. The NHC steric bulk strongly influenced the selectivity of C–H functionalization to give new carbon–heteroatom bonds versus alkene hydroarylation, despite little structural change in the resting state of the catalysts. Studies were performed by reacting C6F5H and H2C═CHER3 (ER3 = SnBu3, GePh3, SiMe3) using catalytic amounts of Ni(COD)2 and NHC ligands IPr, IMes, IBn, and iPr2Im. Catalytic C–H stannylation to give C6F5SnBu3 was facile with all ligands. The catalytic C–H germylation reaction was more difficult than stannylation but was demonstrated using H2C═CHGePh3 to give C6F5GePh3 for all but the largest NHC. The bulkiest NHC, IPr, gave a 96:4 ratio of the hydroarylation product C6F5CH2CH2GePh3 versus C6F5GePh3. The C–H silylation reactions required the highest temperatures and gave selective silylation product C6F5SiMe3 only for the smallest IBn and iPr2Im NHC ligands. Using the larger IMes carbene resulted in a 66:34 mixture of silylation and hydroarylation products, and the largest NHC, IPr, gave exclusive conversion to the hydroarylation product, C6F5CH2CH2SiMe3. DFT calculations are provided that give insight into the mechanism and key reaction steps, such as the relative difficulty of the critical β-Sn, Ge, and Si elimination steps.

Synthesis of 3-Substituted Pyrrolidines via Palladium-Catalyzed Hydroarylation

SummaryMetal-catalyzed reactions have revolutionized synthetic chemistry, allowing access to unprecedented molecular architectures with powerful properties and activities. Nonetheless, some transformations remain sparse in number, or out of reach, even with the diverse modern catalytic chemical arsenal, including bimolecular alkene hydroarylation reactions. We report here a broad-scope, palladium-catalyzed pyrroline hydroarylation process that gives 3-aryl pyrrolidines, a class of small molecules with potency in a diverse range of biological scenarios. Thus, whereas N-acyl pyrrolines usually undergo palladium-catalyzed arylation to give alkene products, the corresponding reactions of N-alkyl pyrrolines deliver products of hydroarylation, pyrrolidines. The process has broad substrate scope and can be used to directly deliver drug-like molecules in a single step from readily available precursors.

Asymmetric Iridium-Catalyzed Hydroarylation of Alkenes

Asymmetric Iridium-Catalyzed Hydroarylation of Alkenes

Catalytic Hydroarylation of Alkenes with Phenols using B(C6F5)3

We demonstrate that tris(pentafluorophenyl)borane, B(C6F5)3, is shown to be an effective catalyst for the hydroarylation of olefins to yield substituted phenols. This system features fast reaction times, mild conditions, and good yields for a select scope of olefinic substrates and various phenols, resulting in C–C bond formation. Experimental data support two possible mechanisms, where the Lewis acid can activate either the olefin or the phenol as the first step in the catalytic mechanism.

Mechanistic Interrogation of Co/Ni-Dual Catalyzed Hydroarylation.

Cobalt/nickel-dual catalyzed hydroarylation of terminal olefins with iodoarenes builds complexity from readily available starting materials, with a high preference for the Markovnikov (branched) product. Here, we advance a mechanistic model of this reaction through the use of reaction progress kinetic analysis (RPKA), radical clock experiments, and stoichiometric studies. Through exclusion of competing hypotheses, we conclude that the reaction proceeds through an unprecedented alkylcobalt to nickel direct transmetalation. Demonstration of catalytic alkene prefunctionalization, via spectroscopic observation of an organocobalt species, distinguishes this Csp2-Csp3 cross-coupling method from a conventional transmetalation process, which employs a stoichiometric organometallic nucleophile, and from a bimetallic oxidative addition of an organohalide across nickel, described by radical scission and subsequent alkyl radical capture at a second nickel center. A refined understanding of the reaction leads to an optimized hydroarylation procedure that excludes exogenous oxidant, demonstrating that the transmetalation is net redox neutral. Catalytic alkene prefunctionalization by cobalt and engagement with nickel catalytic cycles through direct transmetalation provides a new platform to merge these two rich areas of chemistry in preparatively useful ways.

Practical Intermolecular Hydroarylation of Terminal Alkenes via Reductive Heck Coupling.

The hydroarylation of alkenes is an attractive approach to construct carbon-carbon (C-C) bonds from abundant and structurally diverse starting materials. Herein we report a palladiumcatalyzed reductive Heck hydroarylation of unactivated and heteroatom-substituted terminal alkenes with an array of (hetero)aryl iodides. The reaction is anti-Markovnikov selective and tolerates a wide variety of functional groups on both the alkene and (hetero)aryl coupling partners. Additionally, applications of this method to complex molecule diversifications were demonstrated. Deuteriumlabeling experiments are consistent with a mechanism in which the key alkylpalladium(II) intermediate is intercepted with formate and undergoes a decarboxylation/C-H reductive elimination cascade to afford the saturated product and turn over the cycle.

Sulfoximine-Assisted One-Pot Unsymmetrical Multiple Annulation of Arenes: A Combined Experimental and Computational Study.

Discussed herein is an unprecedented Ru-catalyzed one-pot unsymmetrical C-H difunctionalization of arenes comprising intramolecular hydroarylation of olefins and intermolecular annulation of alkynes. This unprecedented 2-fold C-H functionalization is validated on the basis of experimental and density functional theory (DFT) study. The transformation readily occurs with the assistance of methylphenyl sulfoximine (MPS) directing group in the presence of Ru catalyst forming two C-C and one C-N bonds in a single operation. The overall process is atom economical and step-efficient and provides unusual dihydrofuran-fused isoquinolone heterocycles. Further annulation of NH and the proximal o-C-H-arene of isoquinolone with alkynes build highly conjugated novel polycyclic compounds. Overall, three independent annulations in arene motifs are visualized and thoughtfully executed; finally, 5 ring-fused structural entities are constructed forming three C-C and two C-N bonds.

Iron-Nickel Dual-Catalysis: A New Engine for Olefin Functionalization and the Formation of Quaternary Centers.

Alkene hydroarylation forms carbon-carbon bonds between two foundational building blocks of organic chemistry: olefins and aromatic rings. In the absence of electronic bias or directing groups, only the Friedel-Crafts reaction allows arenes to engage alkenes with Markovnikov selectivity to generate quaternary carbons. However, the intermediacy of carbocations precludes the use of electron-deficient arenes, including Lewis basic heterocycles. Here we report a highly Markovnikov-selective, dual-catalytic olefin hydroarylation that tolerates arenes and heteroarenes of any electronic character. Hydrogen atom transfer controls the formation of branched products and arene halogenation specifies attachment points on the aromatic ring. Mono-, di-, tri-, and tetra-substituted alkenes yield Markovnikov products including quaternary carbons within nonstrained rings.

Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C-H Oxidative Addition.

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide ortho-C-H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible.

Rhenium(I)-Catalyzed ortho-C-H Addition to Bicyclic Alkenes.

Hydroarylation of bicyclic alkenes has been developed using a low-valent ReI -catalyzed, directing group-assisted C-H bond activation strategy. The addition of sodium acetate significantly improves the reaction efficiency; moreover, bicyclic alkenes such as 7-oxa and aza benzonorbornadienes worked efficiently under this reaction condition. Preliminary mechanistic studies suggest that, after the alkene insertion, the rhenacycle preferentially undergoes protonolysis rather than reductive elimination.

Rhodium-Catalyzed, Remote Terminal Hydroarylation of Activated Olefins through a Long-Range Deconjugative Isomerization.

The Rh-catalyzed, remote terminal hydroarylation of active olefins at the C7-position of indoles and the ortho-position of indolines and anilines with the appropriate choice of a N-P tBu2 directing group through long-range deconjugative isomerization has been reported. This transformation not only overcomes the conjugate rule of Michael acceptors but also controls the positional selectivity of indoles, representing a significant advancement in both alkene isomerization and the C-H alkylation of indoles.

DMF-Promoted Redox-Neutral Ni-Catalyzed Intramolecular Hydroarylation of Alkene with Simple Arene

A redox-neutral Ni-catalyzed intramolecular hydroarylation of alkene with simple arene has been developed, in which DMF played a proton shuttle role in facilitating the intramolecular coupling, avoiding the use of additional reductants and oxidants. A series of oxindoles with a quaternary center were obtained in up to 99% yield.

Nickel-Catalyzed Enantioselective Pyridone C-H Functionalizations Enabled by a Bulky N-Heterocyclic Carbene Ligand.

Annulated pyridones are an important scaffold found in many biologically active compounds. A Ni(0)-catalyzed C-H functionalization of 2- and 4-pyridones is disclosed, providing access to annulated pyridones via enantioselective intramolecular olefin hydroarylation. Key to the success of the transformation was the development of a sterically hindered and tunable N-heterocyclic carbene ligand resembling a chiral version of IPr. This ligand allows for mild reaction temperatures, and leads to the annulated pyridones in excellent yields and enantioselectivities.

Nickel(0)-catalyzed linear-selective hydroarylation of unactivated alkenes and styrenes with aryl boronic acids.

Herein, we describe the first linear-selective hydroarylation reaction of unactivated alkenes and styrenes with aryl boronic acids, which was achieved by introducing a directing group on the alkenes. This efficient, scalable reaction serves as a method for modular assembly of structurally diverse alkyl arenes, including γ-aryl butyric acid derivatives, which are widely utilized as chemical building blocks for the synthesis of various drugs and other biologically active compounds.