Oxidative Cyclization Reaction of 2‐Aryl‐Substituted Cinnamates To Form Phenanthrene Carboxylates by Using MoCl5

The oxidative cyclization reaction of 2‐aryl cinnamates and derivatives thereof can be easily performed with MoCl₅ as the oxidant. This powerful reagent allows oxidative coupling reactions for which other reagents fail. The best results are obtained when the 2‐phenyl substituent of the cinnamate is equipped with two methoxy groups. Even iodo moieties in the bay region of phenanthrene are tolerated under the reaction conditions. If naphthalene moieties are involved, a rearrangement of the skeleton occurs, providing an elegant route to highly functionalized angular arenes. The cyclization is demonstrated for 15 example substrates with isolated yields of up to 99 % for the phenanthrene derivative. The broad scope of the reaction underlines the usefulness of MoCl₅ and MoCl₅/TiCl₄ in the oxidative coupling reaction.     

Powerful Fluoroalkoxy Molybdenum(V) Reagent for Selective Oxidative Arene Coupling Reaction

We introduce the novel fluoroalkoxy molybdenum(V) reagent 1 which has superior reactivity and selectivity in comparison to MoCl₅ or the MoCl₅/TiCl₄ reagent mixture in the oxidative coupling reactions of aryls. Common side reactions, such as chlorination and/or oligomer formation, are drastically diminished creating a powerful and useful reagent for oxidative coupling. Theoretical treatment of the reagent interaction with 1,2‐dimethoxybenzene‐type substrates indicates an inner‐sphere electron transfer followed by a radical cationic reaction pathway for the oxidative‐coupling process. EPR spectroscopic and electrochemical studies, X‐ray analyses, computational investigations, and the experimental scope provide a highly consistent picture. The substitution of chlorido ligands by hexafluoroisopropoxido moieties seems to boost both the reactivity and selectivity of the metal center which might be applied to other reagents as well.     

Copper‐Catalyzed C(sp3)−H/C(sp3)−H Cross‐Dehydrogenative Coupling with Internal Oxidants: Synthesis of 2‐Trifluoromethyl‐Substituted Dihydropyrrol‐2‐ols

The first oxidative C(sp³)−H/C(sp³)−H cross‐dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper‐catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2‐trifluoromethyldihydropyrrol‐2‐ol derivatives in a highly diastereoselective manner by cascade C(sp³)−C(sp³) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an Aβ₄₂ lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant.     

Stereoselective Formation of Triphenylene Ketals

The oxidative trimerization of catechol ketals by MoCl₅ or MoCl₅/TiCl₄ mixtures leads preferentially to the all‐syn stereoisomer of the corresponding triphenylene ketal. The concomitant metal salts of the oxidative coupling most probably form a multinuclear template that directs the diastereoselectivity in a subsequent isomerization step under electrophilic conditions. Several functionalities can serve as coordination sites for the multinuclear metal chloro clusters. Suitable functional groups have to be stable towards the strong electrophilic and oxidizing conditions. Therefore, esters, nitriles, nitro derivatives, triazoles, and pyridines are successfully employed. Based on the flexibility and size of the substrate, different reagent mixtures lead to the stereoselective formation of the all‐syn derivatives.     

Gold‐Catalyzed Allylation of Aryl Boronic Acids: Accessing Cross‐Coupling Reactivity with Gold

A sp³–sp² C? C cross‐coupling reaction catalyzed by gold in the absence of a sacrificial oxidant is described. Vital to the success of this method is the implementation of a bimetallic catalyst bearing a bis(phosphino)amine ligand. A mechanistic hypothesis is presented, and observable transmetalation, C? Br oxidative addition, and C? C reductive elimination in a model gold complex are shown. We expect that this method will serve as a platform for the development of novel transformations involving redox‐active gold catalysts.     

Photoinduced hydrogen abstraction‐coupling reaction mechanism of Δ5‐steroids with substituted 1, 4‐benzoquinones via electron transfer pathways

The photochemical reaction between three A⁵‐steroids (1–3) and a series of substituted 1,4‐benzoquinones and their mechanistic study were reported. The reaction in nitrogen atmosphere led to the formation of three products including the steroid‐quinone coupling compound (A), 7‐hydroxy derivatives of Δ⁵‐steroids (B) and substituted 1, 4‐hydroquinone (C). Both chemical and spectrometric evidences such as UV‐Visible spectra, ESR, chemically induced dynamic nuclear polarization (CIDNP) and cyclic voltammetry (CV) verified that the title reaction underwent a predominant photoinduced electron transfer pathway via the triplet quinone.     

Tandem Catalytic C(sp3)H Amination/Sila‐Sonogashira–Hagihara Coupling Reactions with Iodine Reagents

A new tandem C? N and C? C bond‐forming reaction has been achieved through Rh^II/Pd⁰ catalysis. The sequence first involves an iodine(III) oxidant, then the in situ generated iodine(I) by‐product is used as a coupling partner. The overall process demonstrates the synthetic value of iodoarenes produced in trivalent iodine reagent mediated oxidations.     

A Pyridine–Pyridine Cross‐Coupling Reaction via Dearomatized Radical Intermediates

A pyridine–pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B₂pin₂ as an electron‐transfer reagent. Complete regio‐ and cross‐selectivity are observed when forming a range of valuable 2,4′‐bipyridines. Phosphonium salts were found to be the only viable radical precursors in this process, and mechanistic studies indicate that the process does not proceed through a Minisci‐type coupling involving a pyridyl radical. Instead, a radical–radical coupling process between a boryl phosphonium pyridyl radical and a boryl‐stabilized cyanopyridine radical explains the C?C bond‐forming step.     

Cu‐Catalyzed Cyanation of Arylboronic Acids with Acetonitrile: A Dual Role of TEMPO

The cyanation of arylboronic acids by using acetonitrile as the “CN” source has been achieved under a Cu(cat.)/TEMPO system (TEMPO=2,2,6,6‐tetramethylpiperidine N‐oxide). The broad substrate scope includes a variety of electron‐rich and electron‐poor arylboronic acids, which react well to give the cyanated products in high to excellent yields. Mechanistic studies reveal that TEMPO?CH₂CN, generated in situ, is an active cyanating reagent, and shows high reactivity for the formation of the CN^? moiety. Moreover, TEMPO acts as a cheap oxidant to enable the reaction to be catalytic in copper.     

Cobalt‐Catalyzed Oxidative C−H/C−H Cross‐Coupling between Two Heteroarenes

The first example of cobalt‐catalyzed oxidative C?H/C?H cross‐coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)₂?4 H₂O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag₂CO₃ oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C?H bond activation pathway that the well‐described oxidative C?H/C?H cross‐coupling reactions between two heteroarenes typically undergo.     

CC Coupling of N‐Heterocycles at the fac‐Re(CO)3 Fragment: Synthesis of Pyridylimidazole and Bipyridine Ligands

A new family of cationic rhenium tricarbonyl complexes with either two N‐alkylimidazole (N‐RIm) and one pyridine (Py) ligand, or two pyridine and one N‐RIm ligand, [Re(CO)₃(N‐RIm)_(3?x)(Py)_x]⁺, has been prepared. The reaction of these complexes with a strong base, followed by an oxidant, selectively afforded 2,2’‐pyridylimidazole complexes as the result of intramolecular dehydrogenative C?C coupling reactions. For tris(pyridine) complexes [Re(CO)₃(Py)₃]⁺ the reaction pattern upon a deprotonation/oxidation sequence is maintained, which allows the generation of complexes with 2,2’‐bipyridine ligands. In the particular combination of two different types of pyridine ligand in the cationic fac‐Re(CO)₃ complexes only the cross‐coupling products with asymmetric 2,2’‐bipyridine ligands were obtained; the homocoupling products were not observed.     

Low-valent Titanium Induced Intramolecular Reductive Coupling of Keto-enamines:A Facile Synthesis of 2,3,5-Trisubstituted Pyrroles

Promoted by low-valent titaium reagent which was generated in situ from Sm/TiCl4 system,keto-enamine derivatives underwent efficient intromolecular deoxygenative coupling reactions and afforded the corresponding 2,3,5-trisubstituted pyrroles in moderate to good yields under mild reaction conditions.     

Microwave‐Accelerated Pd‐Catalyzed Desulfitative Direct C2‐Arylation of Free (NH)‐Indoles with Arylsulfinic Acids

The rapid and efficient direct C2‐arylation of free (NH)‐indoles with arylsulfinic acids proceeded through a microwave‐accelerated palladium‐catalyzed desulfitation reaction. By using PdCl₂ as a catalyst, silver acetate as an oxidant, and H₂SO₄ as an additive, arylsulfinic acids with both electron‐donating and electron‐withdrawing groups underwent desulfitative coupling with an array of free (NH)‐indoles, thereby selectively providing C2‐arylindoles in good yields.     

Ketones from Nickel‐Catalyzed Decarboxylative,Non‐Symmetric Cross‐Electrophile Coupling of Carboxylic Acid Esters

Synthesis of the C?C bonds of ketones relies upon one high‐availability reagent (carboxylic acids) and one low‐availability reagent (organometallic reagents or alkyl iodides). We demonstrate here a ketone synthesis that couples two different carboxylic acid esters, N‐hydroxyphthalimide esters and S‐2‐pyridyl thioesters, to form aryl alkyl and dialkyl ketones in high yields. The keys to this approach are the use of a nickel catalyst with an electron‐poor bipyridine or terpyridine ligand, a THF/DMA mixed solvent system, and ZnCl₂ to enhance the reactivity of the NHP ester. The resulting reaction can be used to form ketones that have previously been difficult to access, such as hindered tertiary/tertiary ketones with strained rings and ketones with α‐heteroatoms. The conditions can be employed in the coupling of complex fragments, including a 20‐mer peptide fragment analog of Exendin(9–39) on solid support.     

Copper‐Catalyzed Radical/Radical CH/PH Cross‐Coupling: α‐Phosphorylation of Aryl Ketone O‐Acetyloximes

The selective radical/radical cross‐coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper‐catalyzed radical/radical C? H/P? H cross‐coupling has been developed. It provides a radical/radical cross‐coupling in a selective manner. This work offers a simple way toward β‐ketophosphonates by oxidative coupling of aryl ketone o‐acetyloximes with phosphine oxides using CuCl as catalyst and PCy₃ as ligand in dioxane under N₂ atmosphere at 130 °C for 5 h, and yields ranging from 47 % to 86 %. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o‐acetyloximes generates iminium radicals, which could isomerize to α‐sp³‐carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o‐acetyloximes and phosphine oxides were suitable for this transformation.     

The Development of Copper‐Catalyzed Aerobic Oxidative Coupling of H‐Tetrazoles with Boronic Acids and an Insight into the Reaction Mechanism

The development of a highly efficient and practical protocol for the direct C?N coupling of H‐tetrazole and boronic acid was presented. A careful and patient optimization of a variety of reaction parameters revealed that this conventionally challenge reaction could indeed proceed efficiently in a very simple system, that is, just by stirring the tetrazoles and boronic acids under oxygen in the presence of different Cu^I or Cu^II salts with only 5 mol % loading in DMSO at 100 °C. Most significantly, the reaction could proceed very smoothly in a regiospecific manner to afford the 2,5‐disubstituted tetrazoles in high to excellent yields. A mechanistic study revealed that both tetrazole and DMSO are crucial for the generation of catalytically active copper species in the reaction process in addition to their role as reactant and solvent, respectively. It is demonstrated that in the reaction cycle, the Cu^I catalyst could be oxidized to Cu^II by oxygen to form a [CuT₂D] complex (T=tetrazole anion; D=DMSO) through an oxidative copper amination reaction. The Cu^II complex thus formed was confirmed to be the real catalytically active copper species. Namely, the Cu^II complex disproportionates to aryl Cu^III and Cu^I in the presence of boronic acid. Facile elimination of the Cu^III species delivers the C?N‐coupled product. The results presented herein not only provide a reliable and efficient protocol for the synthesis of 2,5‐disubstituted tetrazoles, but most importantly, the mechanistic results would have broad implications for the de novo design and development of new methods for Cu‐catalyzed coupling reactions.     

A Highly Efficient Gold‐Catalyzed Photoredox α‐C(sp3)H Alkynylation of Tertiary Aliphatic Amines with Sunlight

A new α‐C(sp³)? H alkynylation of unactivated tertiary aliphatic amines with 1‐iodoalkynes as radical alkynylating reagents in the presence of [Au₂(μ‐dppm)₂]²⁺ in sunlight provides propargylic amines. Based on mechanistic studies, a C? C coupling of an α‐aminoalkyl radical and an alkynyl radical is proposed for the C(sp³)? C(sp) bond formation. The mild, convenient, efficient, and highly selective C(sp³)? H alkynylation reaction shows excellent regioselectivity and good functional‐group compatibility. A scale‐up to gram quantities is possible with sunlight used as a clean and sustainable energy source.     

Copper‐Catalyzed Dehydrogenative Cross‐Coupling Reaction between Allylic CH Bonds and α‐CH Bonds of Ketones or Aldehydes

A dehydrogenative cross‐coupling reaction between allylic C?H bonds and the α‐C?H bond of ketones or aldehydes was developed using Cu(OTf)₂ as a catalyst and DDQ as an oxidant. This synthetic approach to γ,δ‐unsaturated ketones and aldehydes has the advantages of broad scope for both ketones and aldehydes as reactants, mild reaction conditions, good yields and atom economy. A plausible mechanism using Cu(OTf)₂ as a Lewis acid catalyst was also proposed (DDQ=2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone; Tf=trifluoromethanesulfonate).     

Activation of CH Bonds through Oxidant‐Free Photoredox Catalysis: Cross‐Coupling Hydrogen‐Evolution Transformation of Isochromans and β‐Keto Esters

The direct and controlled activation of a C(sp³)?H bond adjacent to an O atom is of particular synthetic value for the conventional derivatization of ethers or alcohols. In general, stoichiometric amounts of an oxidant are required to remove an electron and a hydrogen atom of the ether for subsequent transformations. Herein, we demonstrate that the activation of a C?H bond next to an O atom could be achieved under oxidant‐free conditions through photoredox‐neutral catalysis. By using a commercial dyad photosensitizer (Acr⁺‐Mes ClO₄^?, 9‐mesityl‐10‐methylacridinium perchlorate) and an easily available cobaloxime complex (Co(dmgBF₂)₂?2 MeCN, dmg=dimethylglyoxime), the nucleophilic addition of β‐keto esters to oxonium species, which is rarely observed in photocatalysis, leads to the corresponding coupling products and H₂ in moderate to good yields under visible‐light irradiation. Mechanistic studies suggest that both isochroman and the cobaloxime complex quench the electron‐transfer state of this dyad photosensitizer and that benzylic C?H bond cleavage is probably the rate‐determining step of this cross‐coupling hydrogen‐evolution transformation.     

Cobalt(III)‐Catalyzed Intramolecular Cross‐Dehydrogenative C−H/X−H Coupling: Efficient Synthesis of Indoles and Benzofurans

An efficient cobalt(III)‐catalyzed intramolecular cross‐dehydrogenative C?H/N?H coupling of ortho‐alkenylanilines has been developed utilizing O₂ as a terminal oxidant. The developed reaction tolerates various reactive functional groups and allows the synthesis of diverse indole derivatives in good to excellent yields. The method was successfully extended to the synthesis of benzofurans through the intramolecular cross‐dehydrogenative C?H/O?H coupling of ortho‐alkenylphenols.