Heterobimetallic Reductive Cross-Coupling of Benzonitrile with Carbon Dioxide, Pyridine, and Benzophenone

Stereoselective synthesis of alkenes via base-metal-catalyzed addition reactions to alkynes and activation of hydrogen peroxide and carbon dioxide by iron complexes

The cross-coupling reaction between aryl halides and terminal alkynes, catalyzed by palladium complexes and copper (I) salts, consists in an efficient synthetic tool for the formation of C-C bonds, resulting in disubstituted acetylenic compounds. Accordingly, in this work we present our preliminary results involving the selective cross-coupling reaction between 2,6-diiodoanisoles and terminal alkynes, catalyzed by Pd(PPh 3 ) 2 Cl 2 and CuI, in the formation of 2-iodo-alkynylanisoles (scheme 1).

Synthesis of vinyl nonaflates derived from β-ketoesters, β-diketones or α-diketones and their palladium-catalyzed cross-coupling reactions with organozinc halides

Radical–Radical Cross-Coupling Assisted N–S Bond Formation Using Alternating Current Protocol

The Introduction of the Radical Cascade Reaction into Polymer Chemistry: A One-Step Strategy for Synchronized Polymerization and Modification.

Molybdenum para-Terphenyl Diphosphine Complexes

Unsymmetrical 3,4-disubstituted maleimides have been synthesized by palladium-catalyzed cross-coupling reactions of indium organometallics with 3,4-dihalomaleimides. The synthesis was performed by stepwise or sequential one-pot palladium-catalyzed cross-coupling reactions with various triorganoindium reagents. This method was used to prepare a wide variety of alkyl, aryl, heteroaryl, and alkynyl 3,4-disubstituted maleimides in good yields and with high selectivity and atom economy.

The formation of new bonds through C-C bond formation is of utmost importance in the synthesis of biologically privileged scaffolds and therapeutic drugs. In recent years, extensive efforts has been done to improve the intermolecular and intramolecular cross-coupling reaction in the simple, mild, efficient, economical, and eco-friendly manner via transition metal-free or organocatalytic direct C-H bond activation methodology. The traditional cross-coupling era continuously shifted to metal-free, organocatalytic, or metal-free cross-dehydrogenative coupling strategies to fast-track the reactions and diminishing the typical purification processes. Therefore, recent advances on the transition-metal-free, organocatalytic inter- and intra-molecular cross-coupling reactions have been introduced and discussed in the present article. In view of the reaction mechanism, organocatalytic cross-coupling reactions undergo through radical pathways, radical anionic intermediate which is completely different from traditional transition metal-catalyzed reactions. The exploration of transition metal-free organocatalyzed cross-couplings for direct C-H arylation of arenes has grown significantly, thereby, improving the formation of a wide range of aryl-aryl /arylheteroaryl/ heteroaryl-heteroaryl compounds. In the survey, transition metal-free/organocatalytic cross-coupling reactions showed a higher efficiency under simple and mild conditions than the comparative transition metal-catalyzed cross-coupling reactions. However, the higher regioselectivity and chemoselectivity are still far ahead in organocatalytic cross-coupling reactions due to their specific intrinsic mechanistic pathway. The tuning of many parameters such as oxidative states, ligands coordination, and counter anions, etc., which results in the specific direct C-H functionalization with flexible methodology are missing in the transition metal-free cross-coupling reactions. The highly systematic transition metal-catalyzed chemistry is still playing a dominant role over transition metal-free chemistry in organic synthesis. The organocatalyzed transition-metal-free conditions should be more efficient, chemoselective, and regioselective for further potential development and applications in organic synthesis. For the endless pursuit of sustainable chemistry and green chemistry, such transition-metal-free/organocatalytic reactions should be never ceased. Additional curious attention and interest have been developed so far, and chemists are showing their eagerness and talents to uncover the hidden treasure of green chemistry. In this review article, we highlighted the developments of various transition metal-free/organocatalytic C-H bond activation reactions which further encourages the advancement in the development of sustainable C-C coupling reactions and their further applications towards the synthesis of biologically privileged scaffolds and drug molecules.

Carbon dioxide is the most abundant C1 resource on the Earth, and its resource utilization has been one of the hot spots and the frontiers research of organic chemistry. Among them, the transition metal catalyzed carboxylation reactions with carbon dioxide as carbonyl source provided high atom-economical strategies for the construction of an array of carboxylic acids and their derivatives, which were regarded as one of the most effective approaches for the utilization of carbon dioxide. In recent years, various transition metals such as nickel, copper, palladium, gold, rhodium, cobalt and iron have been widely applied in the carboxylation of carbon dioxide. Based on our research interest in palladium-catalyzed coupling reactions, in this paper, we reviewed the recent research progress of the Pd-catalyzed carboxylation with carbon dioxide as carbonyl source. There are several types of the Pd-catalyzed carboxylation reactions, including: (1) The Pd-catalyzed carboxylation reactions of the carbon dioxide with allylic, butadiene, allenes compounds, respectively, which underwent the nucleophilic addition of σ -allyl palladium species to carbon dioxide; (2) the Pd-catalyzed carboxylation reactions of the carbon dioxide with aryl bromides, aryl triflates, respectively, in which the aryl palladium species were generated via the oxidation addition of aryl reagents with Pd(0), followed by the insertion of carbon dioxide; (3) the Pd-catalyzed carboxylation reactions of the carbon dioxide with unactivated aryl sp2 C−H bonds, which proceeded the concerted-metalation-deprotonation process to produce the palladacycle intermediate, followed by the insertion of two molecules of carbon dioxide into the hetero-palladium bond of palladacycle intermediate; (4) the Pd-catalyzed carboxylation reaction of ethylene and carbon dioxide via the oxidation cycloaddition process to generate five-membered palladalactones intermediate; (5) the Pd-catalyzed carboxylation reactions of carbon dioxide with organozinc reagents, which underwent the transmetalation of Pd-CO2 complex with organozinc reagents to form organopalladium species, followed by the reductive elimination. Although some progress as mentioned above has been made in the Pd-catalyzed carboxylation involving carbon dioxide, there are still some challenges in the catalytic carboxylation reactions, such as the limited substrates scope, harsh reaction conditions, the asymmetric carboxylation reactions, the industrial production of carboxylic compounds, and so on. Therefore, the development of highly effective catalytic systems is the key to address these issues. Palladium catalysts exhibit great potential in the carboxylation of carbon dioxide due to the advantages of versatility, high selectivity and strong functional group tolerance of palladium catalyzed reactions. This paper is intended to provide some advices for the development of palladium-catalyzed carboxylation reactions involving carbon dioxide for the formation of carbon-carbon bonds.

Electron-transfer kinetics of transition-metal complexes in lower oxidation states IV1. Electrochemical electron-transfer rates of tris-(2,2′-bipyridine) complexes of iron, ruthenium, osmium, chromium, titanium, vanadium and molybdenum

Electron-transfer kinetics of transition-metal complexes in lower oxidation states: IV 1. Electrochemical electron-transfer rates of tris(2,2'-bipyridine) complexes of iron, ruthenium, osmium, chromium, titanium, vanadium and molybdenum

Persistent radicals facilitate numerous selective radical coupling reactions. Here, we have identified acyl triazole as a new and versatile moiety for generating persistent radical intermediates through single-electron transfer processes. The efficient generation of these persistent radicals is facilitated by the formation of substrate-coordinated cobalt complexes, which subsequently engage in radical cross-coupling reactions. Remarkably, triazole-coordinated cobalt complexes exhibit metal-hydride hydrogen atom transfer (MHAT) capabilities with alkenes, enabling the efficient synthesis of diverse ketone products without the need for external ligands. By leveraging the persistent radical effect, this catalytic approach also allows for the development of other radical cross-coupling reactions with two representative radical precursors. The discovery of acyl triazoles as effective substrates for generating persistent radicals and as ligands for cobalt catalysis, combined with the bifunctional nature of the cobalt catalytic system, opens up new avenues for the design and development of efficient and sustainable organic transformations.

For the sustainable and economical supply of products relevant to our society, the development of new methods based on main group elements is indispensable. Arenes are privileged molecular scaffolds due to their stability, rigidity and their manifold use in functional or bioactive entities. Nowadays, transition metal catalyzed cross-coupling reactions are the most frequently employed and efficient methods to functionalize arenes by means of C – C bond formation. However, they require prefunctionalized coupling partners and remaining catalyst impurities are difficult to be removed to the required levels. Thus, transition-metal-free methods to synthesize substituted arenes from readily available starting materials are highly desirable. Carboxylic acid ester are ubiquitous intermediates in organic synthesis and are therefore the ideal substrates for the synthesis of arene derivatives. In this thesis the development of a one step transformation of carboxylic acid esters into substituted arenes with 1,5 bifunctional organomagnesium reagents is described. The Grignard reagents react with the esters in a twofold nucleophilic addition, which is followed by an ensuing 1,4 elimination, incorporating the carboxylic carbon-atom into the newly formed aromatic ring. Various arene derivatives like substituted benzenes and polycyclic aromatic hydrocarbons like anthracenes, tetracenes and pentacenes were synthesized in yields up to 99%. The remarkable advancement of mild halogen magnesium exchange reactions over the recent years allowed to access a 1,5-dimagnesium-1,4-pentadiene reagent from the corresponding diiodo-precursor. The reagent was utilized to efficiently convert esters into substituted benzene. Various derivatives such as aryl-, heteroaryl-, alkenyl- and alkyl-substituted benzenes were prepared in yields up to 82% by this direct [5+1]-benzene-forming reaction under mild conditions. The corresponding 1,5 bifunctional bifunctional arylic organomagnesium reagents were obtained by the direct oxidative addition of elemental magnesium into the Ar – Br bond of o,o' dibromoarylmethanes. These reagents show a higher stability in comparison to the pentadiene-Grignard reagent and react with esters at room temperature with extraordinary efficiency. Even mono-substituted pentacenes, sensitive to light and oxygen can be successfully prepared by this mild method in yields up to 97%. An organomagnesium alkoxide reagent prepared by a deprotonation-magnesiation sequence from readily available bis(2-bromophenyl)methanol allowed the synthesis of disubstituted anthracenes and anthrones. Halogen-substituted and reduced derivatives were obtained by variation of the workup conditions in one synthetic step. Workup with aq. HCl (1M) allowed to isolate the corresponding cis-diol in excellent yield. Remarkably, a high level of diastereoselectivity was observed, which presumably is a result of coordination of the alkoxide metal to the ester carboxyl oxygen in the second addition step. Based on this observation, the preparation of a chiral 1,5 bifunctional organomagnesium alkoxide reagent derived from a chiral propargylic alcohol was developed. This allowed to implement a stereoselective direct ester to naphthalene transformation by means of central to axial chirality conversion giving direct access to valuable axially chiral TMS-substituted naphthalenes. Full stereospecificity was observed with substrates with sufficient substitution. Moreover, products with low rotational barriers could be efficiently prepared under the mild reaction conditions with good stereoselectivity. Intriguingly, complete reversal of the stereoselectivity was observed in the transformation of a unprotected deprotonated indole-ester.

Photoredox catalysis can be induced to activate organic substrates or to modulate the oxidation state of transition-metal catalysts via unique single-electron transfer processes, so as to achieve c...

ConspectusIn recent years, radical-mediated cross-coupling reactions have emerged as a compelling strategy for achieving a rich diversity in molecular topologies under benign conditions. However, the inherent high reactivity of radicals presents considerable challenges in controlling reaction pathways and selectivity, which often results in a limited range of substrates and a constrained reaction profile. Given the capacity of visible-light photoredox catalysis to generate a wide variety of reactive radicals and radical ions in a controlled manner and the propensity of copper complexes toward radical species, we envisaged that the synergy between chiral copper catalysts and photoactive catalysts would pave the way for developing innovative strategies. This integration is poised to unlock a broad spectrum of enantioselective multicomponent radical cross-coupling reactions.In this Account, we describe our insights and recent efforts in the realm of enantioselective multicomponent radical cross-coupling reactions. These advancements have been achieved through the innovative application of dual photoredox/copper catalysis or bifunctional copper catalysis under visible light irradiation. Our work is systematically divided into two sections based on the activation modes. The first section focuses on photoinduced copper-catalyzed chiral C-C and C-O bond formation through a radical addition/nucleophilic trap sequence. Our discussion of chiral C-C bond formation is particularly concentrated on the asymmetric carbocyanation and carboarylation of vinylarenes, 1,3-enynes, and 1,3-dienes. Our findings underscore that irradiation with visible light can adeptly modulate the pace of radical generation, thus orchestrating consecutive reaction stages and ensuring the attainment of both chemo- and stereoselectivity. In the domain of chiral C-O bond formation, leveraging carboxylic acids as a nucleophilic oxygen source, we introduce a suite of esterification reactions of benzylic, allylic, and propargylic radicals. These radicals are derived from a variety of radical precursors, showcasing the versatility of our approach. The following section highlights our innovative discovery in the field of dual photoredox/copper catalysis, which enables enantioselective three-component radical transformations via the direct activation of aromatic alkenes. This methodology begins with the generation of formal distonic radical anions through the photocatalytic single-electron reduction of aromatic alkenes, thus, enabling orthogonal reactivity. Employing H2O, D2O, and CO2 as external electrophile agents, we have developed three types of radical cyanofunctionalization reactions: hydrocyanation, deuteriocyanation, and cyanocarboxylation. These reactions provide practical access to diversely functionalized chiral nitriles with high enantiomeric excess.Collectively, these synthetic methodologies highlight the immense potential inherent in the synergistic integration of photocatalysis and asymmetric copper catalysis. This Account aspires to deepen our comprehension of the advantages conferred by these catalytic systems, elucidating the crucial role of photocatalysis in facilitating enantioselective multicomponent radical cross-couplings. We anticipate that this Account will provide valuable insights and stimulate the evolution of innovative methodologies within this rapidly expanding field.