Transition Metal-catalyzed Reactions Research Articles

Electrochemical generation of aryl radicals from organoboron reagents enabled by pulsed electrosynthesis.

Aryl radicals play a pivotal role as reactive intermediates in chemical synthesis, commonly arising from aryl halides and aryl diazo compounds. Expanding the repertoire of sources for aryl radical generation to include abundant and stable organoboron reagents would significantly advance radical chemistry and broaden their reactivity profile. While traditional approaches utilize stoichiometric oxidants or photocatalysis to generate aryl radicals from these reagents, electrochemical conditions have been largely underexplored. Through rigorous mechanistic investigations, we identified fundamental challenges hindering aryl radical generation. In addition to the high oxidation potentials of aromatic organoboron compounds, electrode passivation through radical grafting, homocoupling of aryl radicals, and decomposition issues were identified. We demonstrate that pulsed electrosynthesis enables selective and efficient aryl radical generation by mitigating the fundamental challenges. Our discoveries facilitated the development of the first electrochemical conversion of aryl potassium trifluoroborate salts into aryl C-P bonds. This sustainable and straightforward oxidative electrochemical approach exhibited a broad substrate scope, accommodating various heterocycles and aryl chlorides, typical substrates in transition-metal catalyzed cross-coupling reactions. Furthermore, we extended this methodology to form aryl C-Se, C-Te, and C-S bonds, showcasing its versatility and potential in bond formation processes.

Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions.

Transition metal-catalyzed carbene transfer reactions have a century-old history in organic chemistry and are a primary method for the synthesis of cyclopropanes. Much of the work in this field has focused on the use of diazo compounds and related precursors, which can transfer a carbene fragment to a catalyst with concomitant loss of a stable byproduct. Despite the utility of this approach, there are persistent limitations in the scope of viable carbenes, most notably those lacking stabilizing substituents. By coupling carbene transfer chemistry with two-electron redox cycles, it is possible to expand the available starting materials that can be used as carbene precursors. In this Minireview, we discuss emerging catalytic reductive cyclopropanation reactions using either gem-dihaloalkanes or carbonyl compounds. This strategy is inspired by classic stoichiometric transformations, such as the Simmons-Smith cyclopropanation and the Clemmensen reduction, but instead entails the formation of a catalytically generated transition metal carbene or carbenoid. We also present recent efforts to generate carbenes directly from methylene (CR2H2) groups via a formal dehydrogenation. These reactions are currently restricted to substrates containing electron-withdrawing substituents, which serve to facilitate deprotonation and subsequent oxidation of the anion.

Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives.

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions.

Purple Light-Promoted Coupling of Bromopyridines with Grignard Reagents via SET.

Alkyl- and arylpyridines and 2,2'-bipyridines are conventionally prepared by Minisci reactions of pyridines and transition metal-catalyzed coupling reactions of halopyridines. Herein, purple light-promoted radical coupling reactions of 2- or 4-bromopyridines with Grignard reagents in Et2O or a mixture of Et2O and tetrahydrofuran in regular glassware without the need for a transition metal catalyst were disclosed for the first time. Methyl, primary and secondary alkyl, cycloalkyl, aryl, heteroaryl, pyridyl, and alkynyl Grignard reagents were compatible with the protocol. As a result, alkyl- and arylpyridines and 2,2'-bipyridines were easily prepared. Single electron transfer from the Grignard reagent to bromopyridine was stimulated by purple light. An electron extruded from the dimerization of the Grignard reagent worked as the catalyst. Light on/off experiments indicated that constant irradiation was required for product formation. Studies of radical clock substrates verified the involvement of a pyridyl radical from bromopyridine and the noninvolvement of an alkyl or aryl radical from the Grignard reagent. The available proof supports a photoinduced SRN mechanism for the new coupling reactions.

Carbene-Assisted Arene Ring-Opening.

Despite the significant achievements in dearomatization and C-H functionalization of arenes, the arene ring-opening remains a largely unmet challenge and is underdeveloped due to the high bond dissociation energy and strong resonance stabilization energy inherent in aromatic compounds. Herein, we demonstrate a novel carbene assisted strategy for arene ring-opening. The understanding of the mechanism by our DFT calculations will stimulate wide application of bulk arene chemicals for the synthesis of value-added polyconjugated chain molecules. Various aryl azide derivatives now can be directly converted into valuable polyconjugated enynes, avoiding traditional synthesis including multistep unsaturated precursors, poor selectivity control, and subsequent transition-metal catalyzed cross-coupling reactions. The simple conditions required were demonstrated in the late-stage modification of complex molecules and fused ring compounds. This chemistry expands the horizons of carbene chemistry and provides a novel pathway for arene ring-opening.

Tracking the role of compressive strain in bowl-Like Co-MOFs structural evolution in water oxidation reaction

Dynamic structural evolution of catalyst active sites is crucial to for transition metal-catalyzed oxygen evolution reaction (OER). Yet, the elucidation of their mechanism behind the compressive-strain-induced reconstruction during OER process remains enigmatic. Here, we construct a bowl-like cobalt-based metal-organic frameworks (BL-Co-MOFs) catalyst with compressive strain to investigate the effect of strain on the structural evolution process and the OER mechanism. In situ techniques directly observe that compressive strain exists in the reconstruction of the potential-driven CoOOH-like active phase with contractile interatomic CoCo distance, promoting a direct OO radical coupling over the Co sites (Co−O−O−Co) during the OER process. This disrupts the constrains of the inherent linear scaling relationship and achieves the kinetic-faster oxide path mechanism (OPM) during OER process. Consequently, the BL-Co-MOFs exhibit a huge mass activity of 12516 A gmetal−1 and a large turnover frequency of 6888 h−1 at a low overpotential of 275 mV (300 mA cm−2).

Polydentate Amidinato-Silylenes, -Germylenes and -Stannylenes.

This review article focuses on amidinatotetrylenes that potentially can (or have already shown to) behave as bi- or tridentate ligands because they contain at least one amidinatotetrylene moiety (silylene, germylene or stannylene) and one (or more) additional coordinable fragment(s). Currently, they are being widely used as ligands in coordination chemistry, small molecule activation and catalysis. This review classifies those that have been isolated as transition metal-free compounds into five families that differ in the position(s) of the donor group(s) (D) on the amidinatotetrylene moiety, namely: ED{R1NC(R2)NR1}, EX{DNC(R2)NR1}, EX{R1NC(D)NR1}, EX{DNC(R2)ND} and E{R1NC(R2)ND}2 (E = Si, Ge or Sn). Those that do not exist as transition metal-free compounds but have been observed as ligands in transition metal complexes are cyclometallated and ring-opened amidinatotetrylene ligands. This article presents schematic descriptions of their structures, the approaches used for their syntheses and a quick overview of their involvement (as ligands) in transition metal-catalysed reactions. The literature is covered up to the end of 2023.

Dienes as Versatile Substrates for Transition Metal-Catalyzed Reactions.

Dienes have been of great interest to synthetic chemists as valuable substrates due to their abundance and ease of synthesis. Their unique stereoelectronic properties enable broad reactivity with a wide range of transition metals to construct molecular complexity facilitating synthesis of biologically active compounds. In addition, structural diene variation can result in substrate-controlled reactions, providing valuable mechanistic insights into reactivity and selectivity patterns. The last decade has seen a wealth of new methodologies involving diene substrates through the power of transition metal catalysis. This review summarizes recent advances and remaining opportunities for transition metal-catalyzed transformations involving dienes.

Enantioselective Divergent Syntheses of Diterpenoid Pyrones.

Capitalizing a synergy between late-stage C(sp3)-H alkynylation and a series of transition metal-catalyzed alkyne functionalization reactions, we reported herein enantioselective divergent synthesis of 10 diterpenoid pyrones within 14-16 steps starting from chiral pool enoxolone, including the first enantioselective synthesis of higginsianins A, B, D, E, and metarhizin C. Our synthesis also highlights an unprecedented biomimetic oxidative rearrangement of α-pyrone into 3(2H)-furanone, as well as applications of Echavarren C(sp3)-H alkynylation reaction and Toste chiral counterion-mediated Au-catalyzed intramolecular allene hydroalkoxylation in natural product synthesis.

Gas Evolution as a Tool to Study Reaction Kinetics Under Biomimetic Conditions.

The field of bioorthogonal chemistry is rapidly growing, presenting successful applications of organic and transition metal-catalysed reactions in cells and living systems (in vivo). The development of such reactions typically proceeds through many iterative steps focused on biocompatibility and fast reaction kinetics to ensure product formation. However, obtaining kinetic data, even under simulated biological (biomimetic) conditions, remains a challenge due to substantial concentrations of salts and biomolecules hampering the use of typically employed solution-phase analytical techniques. In this study, we explored the suitability of gas evolution as a probe to study kinetics under biomimetic conditions. As proof of concept, we show that the progress of two transition metal-catalysed bioorthogonal chemical reactions can be accurately monitored, regardless of the complexity of the medium. As such, we introduce a protocol to gain more insight into the performance of a catalytic system under biomimetic conditions to further progress iterative catalyst development for in vivo applications.

Cyclic Diaryl λ3-Bromanes as a Precursor for Regiodivergent Alkynylation Reactions.

Regiodivergent reactions are a fascinating tool to rapidly access molecular diversity while using identical coupling partners. We have developed a new approach for regiodivergent synthesis using the dual character of hypervalent bromines. In addition to the recently reported reactivity of hypervalent bromines as aryne precursors, the first transition metal-catalyzed reaction is reported. Accordingly, the development of these two complementary transformations allows for the alteration of regioselectivity to furnish both ortho- and meta-substituted alkynylation products. Mechanistic and computational studies show how these selectivities are controlled.

Enantioselective Synthesis of the 1,3-Dienyl-5-Alkyl-6-Oxy Motif: Method Development and Total Synthesis.

The 1,3-dienyl-5-alkyl-6-oxy motif is widely found in various types of bioactive natural products. However, present synthesis is mainly non-asymmetric which relied upon different olefination or transition metal-catalyzed cross-coupling reactions using enantioenriched precursors. Herein, based upon a newly developed enantioselective α-alkylation of conjugated polyenoic acids, a variety of 1,3-dienyl-5-alkyl-6-oxy motif (with E-configured internal olefin) was generated as the corresponding α-adducts in a highly enantioselective and diastereoselective manner. Utilizing 1,3-dienyl-5-alkyl-6-oxy motif as key intermediates, we further demonstrated their synthetic potential by expedient total syntheses of three types of natural products (glutarimide antibiotics, α-pyrone polyketides and Lupin alkaloids) within 4-7 steps.

Transition-Metal Catalyzed Synthesis of Pyrimidines: Recent Advances, Mechanism, Scope and Future Perspectives.

Pyrimidine is a pharmacologically important moiety that exhibits diverse biological activities. This review reflects the growing significance of transition metal-catalyzed reactions for the synthesis of pyrimidines (with no discussion being made on the transition metal-catalyzed functionalization of pyrimidines). The effect of different catalysts on the selectivity/yields of pyrimidines and catalyst recyclability (wherever applicable) are described, together with attempts to illustrate the role of the catalyst through mechanisms. Although several methods have been researched for synthesizing this privileged scaffold, there has been a considerable push to expand transition metal-catalyzed, sustainable, efficient and selective synthetic strategies leading to pyrimidines. The aim of the authors with this update (2017-2023) is to drive the designing of new transition metal-mediated protocols for pyrimidine synthesis.

Copper-Catalyzed Sulfimidation in Aqueous Media: a Fast, Chemoselective and Biomolecule-Compatible Reaction.

Performing transition metal-catalyzed reactions in cells and living systems has equipped scientists with a toolbox to study biological processes and release drugs on demand. Thus far, an impressive scope of reactions has been performed in these settings, but many are yet to be introduced. Nitrene transfer presents a rather unexplored new-to-nature reaction. The reaction products are frequently encountered motifs in pharmaceuticals, presenting opportunities for the controlled, intracellular synthesis of drugs. Hence, we explored the transition metal-catalyzed sulfimidation reaction in water for future in vivo application. Two Cu(I) complexes containing trispyrazolylborate ligands (Tpx ) were selected, and the catalytic system was evaluated with the aid of three fitness factors. The excellent nitrene transfer reactivity and high chemoselectivity of the catalysts, coupled with good biomolecule compatibility, successfully enabled the sulfimidation of thioethers in aqueous media. We envision that this copper-catalyzed sulfimidation reaction could be an interesting starting point to unlock the potential of nitrene transfer catalysis in vivo.

Generation and transformation of α-oxy carbene intermediates enabled by copper-catalyzed carbonylation

Since the Fischer-Tropsch reaction was discovered by Otto Roelen in 1938, transition metal-catalyzed carbonylation reactions come in as one of the most important methods for preparing carbonyl-containing and carbon chain-increased compounds. As a result, the field of carbonylation research has received considerable attention over the past decades and continues to increase. With the continuous development of carbonylation and the in-depth study of the mechanism, more mechanistic details and variations have been revealed, which provide more possibilities for organic synthesis. Recently, copper catalysis has been introduced to the carbonylative functionalization of alkenes, thus enabling the rapid assembly of functionalized carbonyl compounds from simple starting materials. In this Account, we summarize the new findings in the Cu-catalyzed borocarbonylation of alkenes based on the generation and transformation of α-oxy carbene intermediates. We believe that the results presented in this Account will further inspire the design of new carbonylation reactions.

Overview of Transition Metal Catalyzed Multicomponent Reactions Based on Trapping of Allylic Electrophiles

AbstractMulticomponent reactions provide an excellent approach toward quaternary carbon centres utilizing convergent chemical reactions in a highly selective manner under one‐pot conditions. The reactivity of substrates and metal catalysts is carefully controlled, precluding the formation of side‐products. In this context, transition metal catalyzed reactions of onium ylides generated via diazo precursors and nucleophiles with a third component (an electrophile) have garnered significant attention. Using an allylic precursor as the electrophilic partner provides opportunities to construct all‐carbon quaternary centres. Furthermore, the presence of an allyl fragment in the multicomponent product serves as a pivotal handle for carrying out subsequent modifications. Several recent studies have employed Rh, Pd, and dual Rh/Pd catalytic systems in multicomponent reactions involving allylic alkylation that proceed via a synergistic or relay pathway. Although not significantly successful, in a few cases, asymmetric induction is achieved through chiral phosphoric acids or chiral phosphine ligands. Limited substrate and catalyst scope and the underlying mechanistic complexities have posed formidable challenges, slowing the advancement of asymmetric reactions. This review provides details of multicomponent reactions using readily available substrates like diazo compounds, allylic carbonates, and nucleophiles (R‐OH, R‐NH2,,etc.) forming complex organic compounds. Our primary objective is to discuss the mechanistic issues that may facilitate the progress in asymmetric reactions in this field.

Recent Advances in Total Synthesis of Prenylated Indole Alkaloids by Transition Metal-Catalyzed Reactions as the Key Step

Recent Advances in Total Synthesis of Prenylated Indole Alkaloids by Transition Metal-Catalyzed Reactions as the Key Step

Observation of inserted oxocarbonyl species in the tantalum cation-mediated activation of carbon dioxide dictated by two-state reactivity.

Reductive activation of carbon dioxide (CO2) has drawn increasing attention as an effective and convenient method to unlock this stable molecule, especially via transition metal-catalyzed reactions. Taking the [TaC4O8]+ ion-molecule complex formed in the laser ablation source as a representative, the reactivity of the tantalum metal cation towards CO2 molecules is explored using infrared photodissociation spectroscopy combined with quantum chemical calculations. The strong absorption in the carbonyl stretching region provides solid evidence for the insertion reactions into CO bonds by the tantalum cation. Two inserted oxocarbonyl products are identified based on the great agreement between the experimental results and simulated infrared spectra of energetically low-lying structures in the singlet and triplet states. The pivotal role of two-state reactivity in driving CO2 activation among three different spin states is rationalized by potential energy surface analysis. Our conclusion provides valuable insight into the intrinsic mechanisms of CO2 activation by the tantalum metal cation, highlighting the affinity of tantalum for CO bond insertion in addition to typical "end-on" binding configurations.

Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenative couplings

Enones are widely explored in synthetic chemistry as fundamental building blocks for a wide range of reactions and exhibit intriguing biological activities that are pivotal for drug discovery. The development of synthetic strategies for highly efficient preparation of enones thereby receives intense attention, in particular through the transition metal-catalyzed coupling reactions. Here, we describe a carbene-catalyzed cross dehydrogenative coupling (CDC) reaction that enables effective assembly of simple aldehydes and alkenes to afford a diverse set of enone derivatives. Mechanistically, the in situ generated aryl radical is pivotal to “activate” the alkene by forming an allyl radical through intermolecular hydrogen atom transfer (HAT) pathway and thus forging the carbon-carbon bond formation with aldehyde as the acyl synthon. Notably, our method represents the first example on the enone synthesis through coupling of “non-functionalized” aldehydes and alkenes as coupling partners, and offers a distinct organocatalytic pathway to the transition metal-catalyzed coupling transformations.

Recent advances in Pd-catalyzed asymmetric cyclization reactions.

Over the past few decades, there have been major developments in transition metal-catalyzed asymmetric cyclization reactions, enabling the convenient access to a wide spectrum of structurally diverse chiral carbo- and hetero-cycles, common skeletons found in fine chemicals, natural products, pharmaceuticals, agrochemicals, and materials. In particular, a plethora of enantioselective cyclization reactions have been promoted by chiral palladium catalysts owing to their outstanding features. This review aims to collect the latest advancements in enantioselective palladium-catalyzed cyclization reactions over the past eleven years, and it is organized into thirteen sections depending on the different types of transformations involved.