Regioselective functionalization of internal alkenes has become a highly efficient approach for preparing stereochemically defined multi-substituted olefins. Unlike traditional methods that require directing groups, activating groups, or active chemical bonds (e.g., halide, pseudo halide, organometallic reagent, etc.), there remains a strong demand for nondirected and selective functionalization of unactivated alkenes with simple coupling partners, both in academic research or industrial applications. Herein, we report the development of a pyridone-oxazoline (Pyoox) type ligand that combines the features of both pyridone and pyridine-oxazoline in assisting Pd-catalyzed olefination. This ligand enables the activation of simple (hetero) arenes and internal alkenes within a single reaction system. A nondirected and regioselective arylation from simple raw materials has been achieved, providing a straightforward route to various trisubstituted olefins in moderate to excellent yields, with excellent regio-/stereocontrol. Experimental and computational studies on mechanisms offer insight into the distinctive properties and performance of this ligand-promoted catalysis. The synthetic utility of this method is further demonstrated by the simplified synthesis and late-stage diversification of bioactive molecules.

A rhodaelectro-catalyzed double dehydrogenative Heck reaction of indole-2-carboxylic acids with alkenes has been developed for the synthesis of pyrano[3,4-b]indol-1(9H)-ones. The weakly coordinating carboxyl group is utilized twice as a directing group to activate the C-H bonds throughout the reaction. This reaction precedes an acceptorless dehydrogenation under exogenous oxidant-free conditions in an undivided cell with a constant current.

Rhodium catalyzed arene alkenylation reactions with arenes and olefins using dioxygen as the direct oxidant (e.g., ACS Catal. 2020, 10, 11519), Cu(II) carboxylates (e.g., Science 2015, 348, 421; J. Am. Chem. Soc. 2017, 139, 5474) or Fe(III) carboxylate clusters (e.g., ACS Catal. 2024, 14, 10295), in the presence or absence of dioxygen, have been reported. These processes involve heating catalyst precursor [(η2-C2H4)2Rh(μ-OAc)]2, olefin, arene, and oxidant at temperatures between 120 and 200 °C. Herein, we report comparative studies of Rh-catalyzed arene alkenylation as a function of oxidant identity. This work includes comparisons of catalysis using Cu(II) carboxylates in the presence and absence of dioxygen, catalysis with only dioxygen as the oxidant, and Fe(III) carboxylates in the presence and absence of dioxygen. We report studies of catalysis with each oxidant including reagent concentration dependencies and kinetic isotope effect experiments using C6H6 or C6D6 and protio- or deutero carboxylic acid. Additionally, we probe ortho/meta/para regioselectivity for reactions of ethylene with monosubstituted arenes and Markovnikov/anti-Markovnikov selectivity with monosubstituted olefins. These studies indicate that the variation of oxidant identity impacts catalyst speciation, the reaction mechanism, and the reaction rate. Consequently, distinct Markovnikov/anti-Markovnikov and ortho/meta/para selectivities are observed for catalysis with each oxidant.

Fe(II) carboxylates react with dioxygen and carboxylic acid to form Fe6(μ-OH)2(μ3-O)2(μ-X)12(HX)2 (X = acetate or pivalate), which is an active oxidant for Rh-catalyzed arene alkenylation. Heating (150-200 °C) the catalyst precursor [(η2-C2H4)2Rh(μ-OAc)]2 with ethylene, benzene, Fe(II) carboxylate, and dioxygen yields styrene >30-fold faster than the reaction with dioxygen in the absence of the Fe(II) carboxylate additive. It is also demonstrated that Fe6(μ-OH)2(μ3-O)2(μ-X)12(HX)2 is an active oxidant under anaerobic conditions, and the reduced material can be reoxidized to Fe6(μ-OH)2(μ3-O)2(μ-X)12(HX)2 by dioxygen. At optimized conditions, a turnover frequency of ∼0.2 s-1 is achieved. Unlike analogous reactions with Cu(II) carboxylate oxidants, which undergo stoichiometric Cu(II)-mediated production of phenyl esters (e.g., phenyl acetate) as side products at temperatures ≥150 °C, no phenyl ester side product is observed when Fe carboxylate additives are used. Kinetic isotope effect experiments using C6H6 and C6D6 give k H/k D = 3.5(3), while the use of protio or monodeutero pivalic acid reveals a small KIE with k H/k D = 1.19(2). First-order dependencies on Fe(II) carboxylate and dioxygen concentration are observed in addition to complicated kinetic dependencies on the concentration of carboxylic acid and ethylene, both of which inhibit the reaction rate at a high concentration. Mechanistic studies are consistent with irreversible benzene C-H activation, ethylene insertion into the formed Rh-Ph bond, β-hydride elimination, and reaction of Rh-H with Fe6(μ-OH)2(μ3-O)2(μ-X)12(HX)2 to regenerate a Rh-carboxylate complex.

We report the conversion of anisoles and olefins to alkenyl anisoles via a transition-metal-catalyzed arene C-H activation and olefin insertion mechanism. The catalyst precursor, [(η2-C2H4)2Rh(μ-OAc)]2, and the in situ oxidant Cu(OPiv)2 (OPiv = pivalate) convert anisoles and olefins (ethylene or propylene) to alkenyl anisoles. When ethylene is used as the olefin, the o/m/p ratio varies between approximately 1:3:1 (selective for 3-methoxystyrene) and 1:5:10 (selective for 4-methoxystyrene). When propylene is the olefin, the o/m/p regioselectivity varies between approximately 1:8:20 and 1:8.5:5. The o/m/p ratios depend on the concentration of pivalic acid and olefin. For example, when using ethylene, at relatively high pivalic acid concentrations and low ethylene concentrations, the o/m/p regioselectivity is 1:3:1. Conversely, again for use of ethylene, at relatively low pivalic acid concentrations and high ethylene concentrations, the o/m/p regioselectivity is 1:5:10. Mechanistic studies of the conversion of anisoles and olefins to alkenyl anisoles provide evidence that the regioselectivity is likely under Curtin-Hammett conditions.

A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.

A cyanoalkyl-hydroxylation reaction of aryl alkenes has been successfully devised, employing ferrocene as a catalyst for the addition of a cycloketone oxime ester and H2O across the double bond of the alkene. This environmentally friendly approach employs a solvent mixture consisting of water and demonstrates redox neutrality, along with exceptional regio- and chemoselectivity, leading to the formation of diverse distal hydroxy-nitrile compounds. Moreover, this research presents noteworthy contributions in terms of late-stage functionalization of complex molecules and offers valuable insights into the mechanistic aspects of the reaction.

Reported herein is a fully orthogonal olefination, which involves the site- and E-selective coupling of aryl germanes with alkenes, tolerating otherwise widely employed coupling handles such as aromatic (pseudo)halogens (C-I, C-Br, C-Cl, C-F, C-OTf, C-OSO2 F), silanes and boronic acid derivatives as well as alternative functionalities. This unprecedented [Ge]-based oxidative Heck coupling proceeds at room temperature with high speed (10 min to 2 hours) and operational simplicity owing to its base-free and air-tolerant features.

We combine experimental and computational investigations to compare and understand catalytic arene alkenylation using the Pd(II) and Rh(I) precursors Pd(OAc)₂ and [(η²-C₂H₄)₂Rh(μ-OAc)]₂ with arene, olefin, and Cu(II) carboxylate at elevated temperatures (>120 °C). Under specific conditions, previous computational and experimental efforts have identified heterotrimetallic cyclic PdCu₂(η²-C₂H₄)₃(μ-OPiv)₆ and [(η²-C₂H₄)₂Rh(μ-OPiv)₂]₂(μ-Cu) (OPiv = pivalate) species as likely active catalysts for these processes. Further studies of catalyst speciation suggest a complicated equilibrium between Cu(II)-containing complexes containing one Rh or Pd atom with complexes containing two Rh or Pd atoms. At 120 °C, Rh catalysis produces styrene >20-fold more rapidly than Pd. Also, at 120 °C, Rh is ∼98% selective for styrene formation, while Pd is ∼82% selective. Our studies indicate that Pd catalysis has a higher predilection toward olefin functionalization to form undesired vinyl ester, while Rh catalysis is more selective for arene/olefin coupling. However, at elevated temperatures, Pd converts vinyl ester and arene to vinyl arene, which is proposed to occur through low-valent Pd(0) clusters that are formed in situ. Regardless of arene functionality, the regioselectivity for alkenylation of mono-substituted arenes with the Rh catalyst gives an approximate 2:1 meta/para ratio with minimal ortho C-H activation. In contrast, Pd selectivity is significantly influenced by arene electronics, with electron-rich arenes giving an approximate 1:2:2 ortho/meta/para ratio, while the electron-deficient (α,α,α)-trifluorotoluene gives a 3:1 meta/para ratio with minimal ortho functionalization. Kinetic intermolecular arene ethenylation competition experiments find that Rh reacts most rapidly with benzene, and the rate of mono-substituted arene alkenylation does not correlate with arene electronics. In contrast, with Pd catalysis, electron-rich arenes react more rapidly than benzene, while electron-deficient arenes react less rapidly than benzene. These experimental findings, in combination with computational results, are consistent with the arene C-H activation step for Pd catalysis involving significant η¹-arenium character due to Pd-mediated electrophilic aromatic substitution character. In contrast, the mechanism for Rh catalysis is not sensitive to arene-substituent electronics, which we propose indicates less electrophilic aromatic substitution character for the Rh-mediated arene C-H activation.

The stilbenes are undoubtedly some of the most significant moieties in various bioactive natural and synthetic structures, and they are considered privileged structures. In recent years, the preparation of these structures via cross-coupling reactions has attracted much attention. In the current review, we present a summary of the recent developments in the construction of stilbene and stilbene derivatives by carbon-carbon coupling reactions of organic compounds in the presence of transition metal catalysts or under metal-free conditions. In this context, we outline the features of the important reactions, some product yields, and challenging reaction mechanisms.

Thermolysis of [^H(BPI)Pt(CH₃)][OTf] (BPI = 1,3-bis(2-(4-tert-butyl)pyridylimino)isoindole) to release methane and form (BPI)Pt(OTf) is reported. Kinetic, mechanistic, and computational studies point to an unusual anion-assisted pathway that obviates the need for a higher oxidation state intermediate to couple the metal-bound methyl group with the ligand-bound hydrogen. Leveraging this insight, a triflimide derivative of the (BPI)Pt complex was shown to activate benzene, highlighting the role of the counteranion in controlling the activity of these complexes.

A base-promoted direct deaminative olefination of organoammonium salts was developed. Only mediated by KO^tBu, a series of benzyl and cinnamyl ammonium salts reacted smoothly with sulfones, producing the valuable stilbenes and related 1,3-diene derivatives in good to high yields with good functional group tolerance and excellent E-selectivity. With this developed method, biologically active resveratrol and DMU-212 were also successfully prepared, which further demonstrates the practicality of this reaction.

Metal catalyzed C-H functionalization offers a versatile platform for methodology development and a wide variety of reactions now exist for the chemo- and site-selective functionalization of organic molecules. Cyclopentadienyl-metal (CpM) complexes of transition metals and their correlative analogues have found widespread application in this area, and herein we highlight several key applications of commonly used transition-metal Cp-type catalysts. In addition, an understanding of transition metal Cp-type catalyst synthesis is important, particularly where modifications to the catalyst structure are required for different applications, and a summary of this aspect is given.

Herein, we realized the multicomponent reactions of phenol derivatives via a six-membered cycloruthenated intermediate for the first time. This strategy exhibited good substrate suitability and functional group tolerance with various phenol derivatives and provided a potential synthetic drug approach. Mechanistic studies showed that a radical might be involved in this process. In addition, the meta alkylated phenol was obtained by further removal of the directing group.

This study shows that various di- and tri-substituted alkenes with high chemoselectivity were obtained in good to high yields by coupling N-tosylhydrazones (NTHs) with benzylic phosphates as electrophilic partners. The obtained new catalytic system consisted of PdCl₂(CH₃CN)₂/dppp, LiOtBu as a base, and cyclopentyl methyl ether as a green solvent. In addition, we performed a gram-scale transformation using NTH derivatives and benzylic phosphates having a C sp²-Cl bond. The latter was used as a starting point for further postfunctionalization of the key intermediates.

Herein we report the synthesis of imidazo[1,5-a]pyridine heterocycles via a Cu(II)-mediated functionalization of α'-C(sp³)-H bonds of pyridinylaldimines and subsequent cyclization. This strategy exploits the inherent directing ability of heteroleptic aldimine and pyridine groups in the substrate yielding the C-H functionalization of α'-methylene groups in a regioselective fashion over distant methyl or methylene groups in β or γ positions. The observed correlation between the nature of the anionic ligands (halide vs. carboxylate) bonded to copper and the chemoselectivity of the C(sp³)-H activation process points to a concerted metalation-deprotonation pathway prior to cyclization to furnish the corresponding imidazo[1,5-a]pyridine derivative. This copper-mediated C(sp³)-H bond functionalization reaction works for a variety of substrates incorporating linear alkyl chains (from 3 to 12 carbon atoms), and good functional group tolerance (aryl, ether and ester groups). Cu-Catalyzed C(sp²)-H cyanation on the imidazole ring can then take place selectively under oxidative conditions.

Energy transfer plays a special role in photocatalysis by utilizing the potential energy of the excited state through indirect excitation, in which a photosensitizer determines the thermodynamic feasibility of the reaction. Bioinspired by the energy-transfer ability of natural product cercosporin, here we developed a green and highly efficient organic photosensitizer HiBRCP (hexaisobutyryl reduced cercosporin) through structural modification of cercosporin. After structural manipulation, its triplet energy was greatly improved, and then, it could markedly promote the efficient geometrical isomerization of alkenes from the E-isomer to the Z-isomer. Moreover, it was also effective for energy-transfer-mediated organometallic catalysis, which allowed realization of the cross-coupling of aryl bromides and carboxylic acids through efficient energy transfer from HiBRCP to nickel complexes. Thus, the study on the relationship between structural manipulation and their photophysical properties provided guidance for further modification of cercosporin, which could be applied to more meaningful and challenging energy-transfer reactions.

A general and effective palladium-catalyzed cross-coupling of organostibines with styrenes to give (E)-olefins was disclosed. By the use of an organostibine reagent, this method can produce unsymmetric (E)-1,2-diarylethylenes and (1E,3E)-1,4-diarylbuta-1,3-dienes in good yields with high E/Z selectivity and good functional group tolerance. Resveratrol and DMU-212 were synthesized in high yield. The protocol can be extended to the synthesis of (1E,3E,5E)-1,6-diphenylhexa-1,3,5-triene in 40% yield. Products 5e, 5f, and 7a showed good photoluminescence quantum yields ranging from 72 to 99%.

On a large scale, the dominant method to produce alkyl arenes has been arene alkylation from arenes and olefins using acid-based catalysis. The addition of arene C-H bonds across olefin C═C bonds catalyzed by transition-metal complexes through C-H activation and olefin insertion into metal-aryl bonds provides an alternative approach with potential advantages. This Perspective presents recent developments of olefin hydroarylation and oxidative olefin hydroarylation catalyzed by molecular complexes based on group 10 transition metals (Ni, Pd, Pt). Emphasis is placed on comparisons between Pt catalysts and other group 10 metal catalysts as well as Ru, Ir, and Rh catalysts.

Rh(III)-catalyzed redox-neutral C-H olefination of aryldiazenecarboxylates has been realized using arylate esters as the olefinating reagents. This reaction proceeds under mild and redox-neutral conditions, resulting in integration of C-H activation and transfer hydrogenation. The chemoselectivity complements that of previously reported rhodium-catalyzed coupling of the same substrates.

Two new iridoid glycosides, genipin 1,10-di-O-α-l-rhamnoside (1) and genipin 1,10-di-O-β-d-xylopyranoside (2), along with thirteen known compounds (3-15) were isolated from Gardeniae Fructus. Their structures were elucidated by physical data analyses such as NMR, UV, IR, HR-ESI-MS, as well as chemical hydrolysis. All compounds were tested for their tyrosinase inhibitory and antioxidant activities. At a concentration of 25 μM, compound 13 showed obvious mushroom tyrosinase inhibition activity with % inhibition value of 36.52 ± 1.98%, with kojic acid used as the positive control (46.09 ± 1.29%). At a concentration of 1 mM, compounds 8 and 9 exhibited considerable DPPH radical scavenging activities, with radical scavenging rates of 48.54 ± 0.47%, 58.59 ± 0.39%, respectively, with l-ascorbic acid used as the positive control (59.02 ± 0.77%).

Photocatalyst-free visible-light-mediated reactions, based on the presence of a visible-light-absorbing functional group in the starting material itself in order to exclude the often costly, hazardous, degradable and difficult to remove or recover photoredox catalysts, have been gaining momentum recently. We have employed this approach to develop a denitrative photocatalyst-free visible-light-mediated protocol for the arylation/sulfonylation of β-nitrostyrenes employing arylazo sulfones (bench-stable photolabile compounds) in a switchable solvent-controlled manner. Arylazo sulfones served as the aryl and sulfonyl radical precursors under blue LED irradiation for the synthesis of trans-stilbenes and (E)-vinyl sulfones in CH3CN and dioxane/H2O 2 : 1, respectively. The absence of any metal, photocatalyst and additive; excellent selectivity (E-stereochemistry) and solvent-switchability; and the use of visible light and ambient temperature are the prime assets of the developed method. Moreover, we report the first photocatalyst-free visible light-driven route to synthesize stilbenes and vinyl sulfones from readily available β-nitrostyrenes.