Catalyzed Cross-coupling Reaction Research Articles

Establishing the main determinants of the environmental safety of catalytic fine chemical synthesis with catalytic cross-coupling reactions

Bio-risk assessment was conducted for Sonogashira and Mizoroki–Heck reactions. bio-Strips showed the cytotoxicity of the reaction components. The study suggests the rules of eco-friendly design for future catalytic processes.

Mechanochemical Synthesis of PdO2 Nanoparticles Immobilized over Silica Gel for Catalytic Suzuki-Miyaura Cross-Coupling Reactions Leading to the C-3 Modification of 1H-Indazole with Phenylboronic Acids.

The C-3 modification of 1H-indazole has produced active pharmaceuticals for the treatment of cancer and HIV. But, so far, this transformation has seemed less available, due to the lack of efficient C-C bond formation at the less reactive C-3 position. In this work, a series of silica gel-supported PdO2 nanoparticles of 25-66 nm size were prepared by ball milling silica gel with divalent palladium precursors, and then employed as catalysts for the Suzuki-Miyaura cross-coupling of 1H-indazole derivative with phenylboronic acid. All the synthesized catalysts showed much higher cross-coupling yields than their palladium precursors, and could also be reused three times without losing high activity and selectivity in a toluene/water/ethanol mixed solvent. Although the palladium precursors showed an order of activity of PdCl2(dppf, 1,1'-bis(diphenylphosphino)ferrocene) > PdCl2(dtbpf, 1,1'-bis(di-tert-butylphosphino)ferrocene) > Pd(OAc, acetate)2, the synthesized catalysts showed an order of C1 (from Pd(OAc)2) > C3 (from PdCl2(dtbpf)) > C2 (from PdCl2(dppf)), which conformed to the orders of BET (Brunauer-Emmett-Teller) surface areas and acidities of these catalysts. Notably, the most inexpensive Pd(OAc)2 can be used as a palladium precursor for the synthesis of the best catalyst through simple ball milling. This work provides a highly active and inexpensive series of catalysts for C-3 modification of 1H-indazole, which are significant for the large-scale production of 1H-indazole-based pharmaceuticals.

Atroposelective NiII -Catalyzed Cross-Coupling Reactions Enable a Deeper Understanding of Negishi Couplings: Isolation and Application of Solid Aryl Higher-Order Zincates.

The Negishi cross-coupling reactions involves the application of organozinc reagents and is a highly versatile reaction in synthetic organic chemistry. The transmetallation step plays a pivotal role in the mechanism of these types of cross-coupling reactions. In this study, mechanistic investigations are presented indicating that higher-order zincates are the transmetallating active species in Pd- and Ni-catalyzed Negishi cross-coupling reactions. These findings are supported by halide salt addition experiments and by obtaining a single X-ray crystal structure of the solid monoaryl higher-order zincate [1-NaphthylZnX3 ]2- Mg(THF)2 2+ . The procedure developed in this work was further applied to the synthesis of various monoaryl higher-order zincates, after which their synthetic usefulness in terms of high reactivity towards transmetallation in Negishi cross-couplings, as well as stability, was exemplified in several reactions.

Milling Medium-Free Suzuki Coupling by Direct Mechanocatalysis: From Mixer Mills to Resonant Acoustic Mixers.

Here we describe the development of a sustainable and cost-effective approach for catalytic cross-coupling reactions in mechanochemistry. It is found that the substrate's impact with the vessel wall alone is sufficient to initiate the reaction, thus indicating that milling balls function primarily as a mixing agent for direct mechanocatalytic Suzuki coupling. The absence of milling balls can be offset by adjusting the rheology using liquid-assisted grinding (LAG). The LAG sweet spot of 0.25 μL mg-1 is confirmed for both resonance acoustic mixers (RAMs) and ball-free mixer mills, and is higher than in the presence of milling balls. RAMs exhibit excellent performance in the Suzuki reaction, achieving yields of 90 % after 60 min and complete conversion after 90 min. The longevity of the milling vessel is significantly improved in a RAM, allowing for at least 20 reactions without deterioration.

ChemCNet: An Explainable Integrated Model for Intelligent Analyzing Chemistry Synthesis Reactions

Palladium (Pd)-catalyzed cross coupling reactions are of great significance in organic synthesis. However, the reaction route is more complex, time-consuming and costly. For addressing the above problems, a model-related feature selection strategy is introduced, focusing on iterative optimization of feature description and prediction to guide and strengthen each other. Then, we combine the lightweight convolution neural network (CNN) driven by attention mechanism with CatBoost to build an intelligent chemical synthesis reaction analysis model-ChemCNet. Moreover, we conduct the interpretability analysis based on ChemCNet model. The results show that ChemCNet model has achieved relatively high prediction accuracy and generalization, and it is helpful to provide reliable decision-making information for the experimenter or institution.

A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions.

ConspectusTransition-metal catalyzed cross-coupling reactions are fundamental reactions in organic chemistry, facilitating strategic bond formations for accessing natural products, organic materials, agrochemicals, and pharmaceuticals. Redox chemistry enables access to elusive cross-coupling mechanisms through single-electron processes as an alternative to classical two-electron strategies predominated by palladium catalysis. The seminal reports of Baran, MacMillan, Doyle, Molander, Weix, Lin, Fu, Reisman, and others in merging redox perturbation (photochemical, electrochemical, and purely chemical) with catalysis are pivotal to the current resurgence and mechanistic understanding of first-row transition metal-based catalysis. The hallmark of this redox platform is the systematic modulation of transition-metal oxidation states by a photoredox catalyst or at a heterogeneous electrode surface. Electrocatalysis and photocatalysis enhance transition metal catalysis' capacity for bond formation through electron- or energy-transfer processes that promote otherwise challenging elementary steps or elusive mechanisms. Cross-coupling conditions promoted by electrocatalysis and photocatalysis are mild, and bond formation proceeds with exceptionally high chemoselectivity and wide functional group tolerance. The interfacing of abundant first-row transition-metal catalysis with electrocatalysis and photocatalysis has brought about a paradigm shift in cross-coupling technology as practitioners are quickly applying these tools in synthesizing fine chemicals and pharmaceutically relevant motifs. In particular, the merger of Ni catalysis with electro- and photochemistry ushered in a new era for carbon-carbon and carbon-heteroatom cross-couplings with expanded generality compared to their thermally driven counterparts. Over the past decade, we have developed enabling photo- and electrochemical methods throughout our combined research experience in industry (BMS, AstraZeneca) and academia (Professor Baran, Scripps Research) in cross-disciplinary collaborative environments. In this Account, we will outline recent progress from our past and present laboratories in photo- and electrochemically mediated Ni-catalyzed cross-couplings. By highlighting these cross-coupling methodologies, we will also compare mechanistic features of both electro- and photochemical strategies for forging C(sp2)-C(sp3), C(sp3)-C(sp3), C-O, C-N, and C-S bonds. Through these side-by-side comparisons, we hope to demystify the subtle differences between the two complementary tools to enact redox control over transition metal catalysis. Finally, building off the collective experience of ourselves and the rest of the community, we propose a tactical user guide to photo- and electrochemically driven cross-coupling reactions to aid the practitioner in rapidly applying such tools in their synthetic designs.

Recent Advances in Design and Synthesis of 1,3-Thiaselenolane and 1,3-Thiaselenole Derivatives

Recent advances in the design and synthesis of five-membered heterocycles containing both sulfur and selenium atoms—1,3-thiaselenolane and 1,3-thiaselenole derivatives—are discussed in this review. These heterocyclic systems are of interest as intermediates for organic synthesis and compounds that can exhibit various useful properties, including biological activity and electrical conductivity. The main focus of the review is on the works of the last 20 years that make use of catalytic reactions. Synthetic methods for the preparation of structurally related 1,4,5,8-diselenadithiafulvalenes based on catalytic cross-coupling reactions are also presented. To date, the design and synthesis of 1,3-thiaselenolane and 1,3-thiaselenole derivatives have not been discussed in a separate review.

1,2-Diborylsilanes: Catalytic Enantioselective Synthesis and Site-Selective Cross-Coupling.

A Pt-catalyzed enantioselective hydrosilylation of (Z)-1,2-diborylethylene provides a 1,2-diboryl-1-silylalkane that can be used in catalytic cross-coupling reactions. Depending on the catalyst employed and the cross-coupling reaction conditions, the coupling can occur at either α or β relative to the silane center.

Regioselective C-F Bond Transformations of Silyl Difluoroenolates.

Herein, we report the development of a nickel-catalyzed cross-coupling reaction of silyl difluoroenolates with aryl zinc reagents via C-F bond cleavage. Treatment of a stoichiometric amount of Ni(0)/N-heterocyclic carbene (NHC) with silyl difluoroenolates in the presence of a lithium salt resulted in C-F bond cleavage to selectively afford the corresponding (Z)-alkenyl Ni complexes. On the basis of the observations, we developed a catalytic cross-coupling reaction that selectively delivers a single geometric isomer of a fluoroenolate.

Synthesis of 2-Formyl Carbazoles via Tandem Reaction of Indolyl Nitrones with 2-Methylidene Cyclic Carbonate.

The synthesis of functionalized carbazoles as privileged nitrogen heterocycles has emerged as a central topic in drug discovery and material science. We herein disclose the rhodium(III)-catalyzed cross-coupling reaction between indolyl nitrones and 2-methylidene cyclic carbonate as an allylating surrogate, resulting in the formation of C2-formylated carbazoles via tandem C-H allylation, [3 + 2] cycloaddition, aromatization, and benzylic oxidation. The synthetic utility of this protocol is highlighted by a variety of post-transformations of C2-formylated carbazoles.

Enantioselective Radical-Type 1,2-Alkoxy-Phosphinoylation to Styrenes Catalyzed by Chiral Vanadyl Complexes.

A series of vanadyl complexes bearing 3-t-butyl-5-bromo, 3-aryl-5-bromo, 3,5-dihalo-, and benzo-fused N-salicylidene-tert-leucinates was examined as catalysts for 1,2-alkoxy-phosphinoylation of 4-, 3-, 3,4-, and 3,5-substituted styrene derivatives (including Me/t-Bu, Ph, OR, Cl/Br, OAc, NO2 , C(O)Me, CO2 Me, CN, and benzo-fused) with HP(O)Ph2 in the presence of t-BuOOH (TBHP) in a given alcohol or cosolvent with MeOH. The best scenario involved the use of 5 mol % 3-(2,5-dimethylphenyl)-5-Br (i.e., 3-DMP-5-Br) catalyst at 0 °C in MeOH. The desired catalytic cross coupling reactions proceeded smoothly with enantioselectivities of up to 95 % ee of (R)-configuration as confirmed by X-ray crystallographic analysis of several recrystallized products. The origin of enantiocontrol and homolytic substitution of the benzylic intermediates by vanadyl-bound methoxide and radical type catalytic mechanism were proposed.

Enantioselective Radical‐Type 1,2‐Alkoxy‐Phosphinoylation to Styrenes Catalyzed by Chiral Vanadyl Complexes

AbstractA series of vanadyl complexes bearing 3‐t‐butyl‐5‐bromo, 3‐aryl‐5‐bromo, 3,5‐dihalo‐, and benzo‐fused N‐salicylidene‐tert‐leucinates was examined as catalysts for 1,2‐alkoxy‐phosphinoylation of 4‐, 3‐, 3,4‐, and 3,5‐substituted styrene derivatives (including Me/t‐Bu, Ph, OR, Cl/Br, OAc, NO2, C(O)Me, CO2Me, CN, and benzo‐fused) with HP(O)Ph2 in the presence of t‐BuOOH (TBHP) in a given alcohol or cosolvent with MeOH. The best scenario involved the use of 5 mol % 3‐(2,5‐dimethylphenyl)‐5‐Br (i.e., 3‐DMP‐5‐Br) catalyst at 0 °C in MeOH. The desired catalytic cross coupling reactions proceeded smoothly with enantioselectivities of up to 95 % ee of (R)‐configuration as confirmed by X‐ray crystallographic analysis of several recrystallized products. The origin of enantiocontrol and homolytic substitution of the benzylic intermediates by vanadyl‐bound methoxide and radical type catalytic mechanism were proposed.

Catalytic Asymmetric Imine Cross-Coupling Reaction

Catalytic asymmetric cross-coupling of imines constitutes a particularly desirable method for the synthesis of chiral vicinal diamines directly from readily available achiral precursors. The potential of this method lies in the possibility of utilizing a variety of imines as reacting partners. However, the realization of highly stereoselective cross-coupling of two different imines proved to be a formidable challenge. Herein we report an unprecedented catalytic asymmetric cross-coupling reaction that tolerates a variety of ketimines and aldimines as nucleophiles and electrophiles, respectively. The realization of this reaction resulted from the development of a new chiral ammonium catalyst, which was guided by insights from studies of catalyst-substrate interactions. With a 0.5 mol % loading of an organocatalyst, this reaction proceeded in a highly diastereo- and enantioselective manner to afford a diverse range of chiral vicinal diamines as nearly single stereoisomers. This catalytic reaction establishes a new approach for the asymmetric synthesis of chiral vicinal diamines.

Induction heating enables efficient heterogeneous catalytic reactions over superparamagnetic nanocatalysts

Most catalytic processes are achieved by heating the whole reaction systems including the entire reactor, substrate and solvent, which leads to energy loss and obvious heat transfer limits. In this study, induction heating was employed to boost the catalytic Suzuki-Miyaura cross-coupling reactions by using conductive superparamagnetic microspheres with loaded Pd nanoparticles as heterogeneous catalysts. It was found that, at the same apparent reaction temperatures, the reactions by adopting the induction heating all exhibit better catalytic performance with higher conversion and yield, as compared to the reactions using conventional joule heating. The improvement is mainly attributed to the localized heating effect endowed by high efficiency of the heat transfer from the heat source to catalytic sites, which dissipates the electromagnetic energy through Néel relaxation mechanism. Moreover, it has be found that the reactions have been largely accelerated, resulting in much shorter reaction time required to approach a given value of reactant conversion. These results indicate that the unique heating method based on the superparamagnetic nanomaterials as both the inductive component and catalyst support holds a promising application for fast and efficient heterogeneous catalytic process, and exhibits potential for improving energy transfer efficiency and reducing the side reactions attributed to the uneven temperature profile.

Photocatalyst-engineering-promoted sulfonamidation of aryl halides via metallaphotoredox

In this issue of Chem Catalysis, Hou and co-workers demonstrate the integrated Ni/nitrogen-vacancy engineered carbon nitride for the synthesis of valuable aryl sulfonamide building blocks driven by visible light. Mechanistic investigation and the unprecedented substrate scope highlight the potential of photocatalyst modulation in achieving challenging metallaphotoredox catalytic cross-coupling reactions.

Transition-Metal-Catalyzed C-S, C-Se, and C-Te Bond Formations via Cross-Coupling and Atom-Economic Addition Reactions. Achievements and Challenges.

In the present review, we discuss recent progress in the field of C-Z bond formation reactions (Z = S, Se, Te) catalyzed by transition metals. Two complementary methodologies are considered─catalytic cross-coupling reactions and catalytic addition reactions. The development of advanced catalytic systems is aimed at improved catalyst efficiency, reduced catalyst loading, better cost efficiency, environmental concerns, and higher selectivity and yields. The important rise of research efforts in sustainability and green chemistry areas is critically assessed. The paramount role of mechanistic studies in the development of a new generation of catalytic systems is addressed, and the key achievements, problems, and challenges are summarized for this field.

Palladium catalyzed radical relay for the oxidative cross-coupling of quinolines

Traditional approaches for transition-metal catalyzed oxidative cross-coupling reactions rely on sp2-hybridized starting materials, such as aryl halides, and more specifically, homogeneous catalysts. We report a heterogeneous Pd-catalyzed radical relay method for the conversion of a heteroarene C(sp3)–H bond into ethers. Pd nanoparticles are supported on an ordered mesoporous composite which, when compared with microporous activated carbons, greatly increases the Pd d charge because of their strong interaction with N-doped anatase nanocrystals. Mechanistic studies provide evidence that electron-deficient Pd with Pd–O/N coordinations efficiently catalyzes the radical relay reaction to release diffusible methoxyl radicals, and highlight the difference between this surface reaction and C–H oxidation mediated by homogeneous catalysts that operate with cyclopalladated intermediates. The reactions proceed efficiently with a turn-over frequency of 84 h−1 and high selectivity toward ethers of >99%. Negligible Pd leaching and activity loss are observed after 7 catalytic runs.

Pd-Catalyzed Cross-Couplings: On the Importance of the Catalyst Quantity Descriptors, mol % and ppm.

This Review examines parts per million (ppm) palladium concentrations in catalytic cross-coupling reactions and their relationship with mole percentage (mol %). Most studies in catalytic cross-coupling chemistry have historically focused on the concentration ratio between (pre)catalyst and the limiting reagent (substrate), expressed as mol %. Several recent papers have outlined the use of “ppm level” palladium as an alternative means of describing catalytic cross-coupling reaction systems. This led us to delve deeper into the literature to assess whether “ppm level” palladium is a practically useful descriptor of catalyst quantities in palladium-catalyzed cross-coupling reactions. Indeed, we conjectured that many reactions could, unknowingly, have employed low “ppm levels” of palladium (pre)catalyst, and generally, what would the spread of ppm palladium look like across a selection of studies reported across the vast array of the cross-coupling chemistry literature. In a few selected examples, we have examined other metal catalyst systems for comparison with palladium.

Palladium catalyzed cross-coupling of 3-methylthiophene-2-carbonyl chloride with aryl/het-aryl boronic acids: a convenient method for synthesis of thienyl ketones

Bi-aryl ketones are important motifs in large number of pharmaceutical compounds and natural products. A protocol for the synthesis of thienyl ketones has been developed via Pd (0) catalyzed cross-coupling reaction. The desired thienyl ketones (3a-x) were synthesized by cross coupling of 3-methylthiophene-2-carbonyl chloride with variety of aryl/heteroaryl-boronic acids in good to excellent yields (46–91%) under mild conditions (1.5 eq Cs2CO3 at 50 °C). Different functional groups were well tolerated under the developed reaction conditions.

Development of Catalytic Cross-Coupling Reactions Based on Transition Metal→Z-type Ligand Interactions

Development of Catalytic Cross-Coupling Reactions Based on Transition Metal→Z-type Ligand Interactions