Alkenylation Products Research Articles

Cobalt-catalyzed chemoselective alkenylation and alkylation of C(sp3)–H bond in methyl heteroarenes

Chemoselective synthesis allows for the generation of diverse products from identical starting materials, which is a significant strategy to build molecular diversity rapidly. By employing acceptorless dehydrogenation and borrowing hydrogen strategies, we herein report a cobalt-catalyzed chemoselective C(sp3)–H bond functionalization of methyl heteroarenes, the alkenylation and alkylation products are obtained using alcohol as the coupling partner under different reaction conditions. The scopes of both arenes and alcohols, synthetic applications, preliminary mechanistic studies, and a proposed mechanism were presented.

Regioselective Alkynylation and Alkenylation at the More Hindered C-B Bond of 1,2-Bis(Boronic) Esters.

Selective transformations at the more sterically hindered sites of organic molecules represent a frontier in the ability to precisely modify molecules. The lack of effective synthetic methods stands in stark contrast to the large number of encumbered sites encountered in molecules of interest. Here, we demonstrate that 1,2-bis(boronates) undergo selective alkynylation and alkenylation at the more sterically hindered C-B bond. Our preliminary mechanistic studies disclosed that this reaction can proceed through two convergent pathways involving direct coupling of sterically encumbered site versus 1,2-boron migratory coupling. Notably, this method facilitated convenient access to alkenyl and alkynyl boron products, which can be diversified by an array of transformations.

Radical-Mediated Decarboxylative C-C and C-S Couplings of Carboxylic Acids via Iron Photocatalysis.

Despite the significant success of decarboxylative radical reactions, the catalytic systems vary considerably upon different radical acceptors, requiring renewed case-by-case reaction optimization. Herein, we developed an iron catalytic condition that enables the highly efficient decarboxylation of various carboxylic acids for a range of radical transformations. This operationally simple protocol was amenable to a wide array of radical acceptors, delivering structurally diverse oxime ethers, alkenylation, alkynylation, thiolation, and amidation products in useful to excellent yields (>40 examples, up to 95% yield).

Transformations of cage alcohols in the presence of 2-propanol and H2SO4

A convenient approach for the synthesis of hydrocarbons by transformations of cage alcohols in the presence of 2-propanol and sulfuric acid has been proposed. Scalability, good yields and usage of readily available reagents along with synthetic convenience showed usefulness of proposed approach. This approach made it possible to obtain high preparative yields of difficult-to-reach cage hydrocarbons such as 2-methyladamantane, 2-phenyladamantane and homoadamantane. For some substrates, the potential to obtain corresponding saturated hydrocarbons or alkenylation products by varying the concentration of sulfuric acid under reaction conditions has been demonstrated.

Palladium-catalyzed regioselective synthesis of mono and bis(arylthiol) alkenes from propargyl carbonate and thiophenol.

A palladium catalyzed regioselective reaction of propargylic carbonate with thiophenols and benzene selenol is described. Atom-economic addition of thiols to propargylic carbonates provides an excellent opportunity for effective processes. The reaction proceeds via hydrothiolation to produce mono(arylthiol) alkenes and hydrothiolation followed by Tsuji-Trost type substitution to form bis(arylthiol) alkenes through single and double sequential attack by soft thio nucleophiles by control of the equivalence of thiophenols. This coupling reaction with good tolerance towards functional groups in both propargylic carbonates and thiols furnished a variety of highly functionalized alkenylation products in moderate to excellent yields via the formation of new C-S and C-Se bonds.

Scandium-Catalyzed Benzylic C(sp3)-H Alkenylation of Tertiary Anilines with Alkynes.

This work describes the chemo- and stereoselective benzylic C(sp3)-H alkenylation of tertiary ortho-methyl anilines with internal alkynes using a simple β-diketiminato scandium catalyst. This protocol offers an efficient method for the synthesis of a new family of tertiary ortho-allylanilines in high yields. The resultant alkenylation products facilely underwent further chemical transformation to other valuable anilines. A cationic scandium benzyl species was isolated from a stoichiometric reaction and confirmed to be the catalytic intermediate.

Mechanism and Origin of Stereoselectivity of Ni-Catalyzed Cyclization/Carboxylation of Bromoalkynes with CO2.

Bromoalkynes play important roles in coupling reactions because they can show obvious stereoselectivity to form E- and Z-isomers when substituents are different. However, the origin of the stereoselectivity in the bromoalkynes reaction is still unclear. Density functional theory (DFT) calculations were performed to provide an in-depth study of the reaction mechanism, clarifying the mechanistic details of the main reaction and the origin of the stereoselectivity. By comparing the syn-insertion mechanism of alkynes and the radical pathway, it is indicated that the electrostatic effect caused by the different charge distributions of the reactants is the main reason that Ni(I) species are more prone to syn-insertion of alkynes than Ni(II) species. In addition, the lower reaction energy barrier in the radical pathway suggests that it is more advantageous in terms of kinetics. The bond between Ni(I) species and alkenylation products has two directions to generate products of different configurations, which are the direct stereoselectivity-determining stages. The distortion/interaction analysis shows that the distortion energy mainly affects the product configuration, and the steric hindrance is the main factor controlling the stereoselectivity.

Monodisperse CoPd nanoparticles supported on reduced graphene oxide as recyclable catalyst for the C(sp2)−H activation

Monodisperse CoxPdy alloy nanoparticles supported on reduced graphene oxide (CoxPdy @rGO) were synthesized and served as an efficient and recyclable catalyst for the chelation-assisted ortho C–H bond the alkenylation and cyclization of benzamides. The effect of the metal composition in CoxPdy on the catalytic activity was studied, and it was found that there is a synergistic effect between the Co and Pd. The rGO has been proved to play a crucial role in preventing aggregation of alloy nanoparticles, maintaining good dispersion, high catalytic activity and stability. Controllable synthesis of alkenylation and cyclization products can be achieved by modifying the reaction conditions. In addition, the catalyst was stable and recyclable, and the activity decay in the recovery and scale-up experiments is negligible, providing a mild and highly efficient method for direct C(sp2)−H functionalization.

Neosilyllithium‐Catalyzed Hydroboration of Alkynes and Alkenes in the Presence of Pinacolborane (HBpin)

AbstractWe report here a novel protocol for the hydroboration of alkynes and alkenes, which in the presence of neosilyllithium (LiCH2SiMe3) (5 mol %) and pinacolborane efficiently results in the formation of corresponding alkenyl and alkyl boronate ester products in good yields. The electron‐donating and electron‐withdrawing substituents on the aromatic rings of alkynes and alkenes converted smoothly to the desired products. When we extended the scope of reactivity to various aliphatic alkynes and styrenes using similar conditions, the alkenyl and alkyl boronate ester products were again formed in good yields. We also performed intramolecular and intermolecular reactions to check the reactivity of different functional groups on the phenyl ring. Experimental investigations and DLPNO‐CCSD(T) calculations reveal mechanistic insights from the LiCH2SiMe3‐catalyzed alkyne hydroboration.

Front Cover: Ruthenium(II)‐Catalyzed Direct Ortho Functionalization of 1‐Arylpyrazoles with Maleimides: A Condition Controlled Installation of Succinimides and Maleimides on Arenes (Asian J. Org. Chem. 9/2021)

Ruthenium(II)-catalyzed switchable ortho C−H activation of 1-arylpyrazoles with maleimides has been achieved. This divergent reaction selectively installs various succinimide and maleimide substituents on the aromatic ring of 1-arylpyrazoles. Depending on the acidic or basic reaction conditions, a wide range of alkylation and alkenylation products are obtained, without the formation of bis-adducts. More information can be found in the Full Paper by Y. R. Lee and co-workers.

Experimental and theoretical investigation of the reaction of a 3-amidothiophene derivative with various carbonyl compounds.

The reactions of a 3-amidothiophene derivative, which is a partial structure of penthiopyrad, with various carbonyl compounds were investigated. Depending on the carbonyl compound that was used as a reactant, different products (alkenes and bis-products) were obtained from the attack of the carbon at the 2-position of the 3-amidothiophene on the carbonyl compounds. Density functional theory (DFT) calculations revealed that dehydration conditions were important for the first carbonyl addition to shift the reaction toward the product, as the products are more unstable than reactants other than aldehyde. The DFT calculations also suggested that the relative stability of the alkenyl state determined whether the second bis-product formation would proceed; i.e., the relatively unstable disubstituted alkene led to bis-products, and the stable trisubstituted or conjugated alkene yielded alkenyl products.

Acid- and Base-Switched Palladium-Catalyzed γ-C(sp3)-H Alkylation and Alkenylation of Neopentylamine.

The functionalization of remote unactivated C(sp3)-H and the reaction selectivity are among the core pursuits for transition-metal catalytic system development. Herein, we report Pd-catalyzed γ-C(sp3)-H-selective alkylation and alkenylation with removable 7-azaindole as a directing group. Acid and base were found to be the decisive regulators for the selective alkylation and alkenylation, respectively, on the same single substrate under otherwise the same reaction conditions. Various acrylates were compatible for the formation of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. The alkenylation protocol could be further extended to acrylates with natural product units and α,β-unsaturated ketones. The preliminary synthetic manipulation of the alkylation and alkenylation products demonstrates the potential of this strategy for structurally diverse aliphatic chain extension and functionalization. Mechanistic experimental studies showed that the acidic and basic catalytic transformations shared the same six-membered dimer palladacycle.

A Water-Soluble Rhenium(I) Catalyst for the Regio- and Stereoselective C(sp2)-H Alkenylation of N-Pyridyl-/N-Pyrimidylindole and the N-H Alkenylation of N-Pyrimidylaniline Derivatives with Ynamides.

A water-soluble and low-valent rhenium(I) catalyst for the C2 alkenylation of N-pyridyl/N-pyrimidylindole derivatives with ynamides under mild conditions using water as the solvent has been described. The reaction of N-pyridyl/N-pyrimidyl indole with the ynamide afforded the C2-Z-selective alkenylation derivative as the sole product, and the reactions of N-pyrimidylanilines delivered the corresponding N-alkenylated product rather than the expected C-H alkenylation products in high yields under the same conditions.

Nickel‐Catalyzed, Regio‐ and Enantioselective Benzylic Alkenylation of Olefins with Alkenyl Bromide

AbstractA NiH‐catalyzed migratory hydroalkenylation reaction of olefins with alkenyl bromides has been developed, affording benzylic alkenylation products with high yields and excellent chemoselectivity. The mild conditions of the reaction preclude olefinic products from undergoing further isomerization or subsequent alkenylation. Catalytic enantioselective hydroalkenylation of styrenes was achieved by using a chiral bisoxazoline ligand.

Nickel-Catalyzed, Regio- and Enantioselective Benzylic Alkenylation of Olefins with Alkenyl Bromide.

A NiH-catalyzed migratory hydroalkenylation reaction of olefins with alkenyl bromides has been developed, affording benzylic alkenylation products with high yields and excellent chemoselectivity. The mild conditions of the reaction preclude olefinic products from undergoing further isomerization or subsequent alkenylation. Catalytic enantioselective hydroalkenylation of styrenes was achieved by using a chiral bisoxazoline ligand.

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids: Construction of Oxindoles Bearing Quaternary Carbons

We have developed a nickel- nickel/bisphosphine-catalyzed stereoconvergent cross-coupling reaction of epoxides with alkenylboronic acids. Racemic spiroepoxyoxindoles were converted to chiral homoal...

Iridium-catalyzed, ligand-controlled directed alkynylation and alkenylation of arenes with terminal alkynes.

We report iridium-catalyzed C-C formation between benzamides and terminal alkynes. With the choice of a suitable ligand, a C-H alkynylation or alkenylation product could be obtained selectively. The directed C-H alkynylation proceeded without the need for an external oxidant, while the directed C-H alkenylation likely involves an unusual vinylidene mechanism. This divergent reactivity provides access to both alkynylation and alkenylation products from the same set of starting materials.

Rhodium(III)-catalysed decarboxylative C-H functionalization of isoxazoles with alkenes and sulfoxonium ylides.

Decarboxylative C-H functionalization of isoxazoles with electron-deficient alkenes and sulfoxonium ylides at the C5 position was achieved in the presence of rhodium(iii) catalysts to give the corresponding alkenylation and acylmethylation products, respectively.

Mechanism and origins of regioselectivities of Rh-catalyzed alkenylation of allylbenzenes.

Rhodium-catalyzed alkenylation of allylbenzene derivatives via C-C bond activation provides an unprecedented access to alkenylation products with remarkable regioselectivities. Using DFT calculations, we elucidate the reaction mechanism and the origins of the regioselectivity.

Formal Lossen Rearrangement/Alkenylation or Annulation Cascade of Heterole Carboxamides with Alkynes Catalyzed by CpRhIII Complexes with Pendant Amides.

It has been established that a cyclopentadienyl (Cp) RhIII complex with two aryl groups and a pendant amide moiety catalyzes the formal Lossen rearrangement/alkenylation cascade of N-pivaloyl heterole carboxamides with internal alkynes, leading to alkenylheteroles. Interestingly, the use of sterically demanding internal alkynes afforded not the alkenylation but the [3+2] annulation products ([5,5]-fused heteroles). In these reactions, the pendant amide moiety of the CpRhIII complex may accelerate the formal Lossen rearrangement. The use of five-membered heteroles may deter reductive elimination to form strained [5,5]-fused heteroles; instead, protonation proceeds to give the alkenylation products. Bulky alkyne substituents accelerate the reductive elimination to allow the formation of the [5,5]-fused heteroles.