Bond-forming Reactions Research Articles

Merging Chiral Diamine and Ni/SiO2 for Heterogeneous Asymmetric 1,4-Addition Reactions

The development of chiral solid catalysts using strategies different from conventional heterogenization methods is of great importance for efficient heterogeneous asymmetric catalysis. Herein, we report the preparation of a chiral solid catalyst, chiral diamine modified Ni/SiO2, for asymmetric Michael addition, a representative carbon–carbon bond-forming reaction. With dimethyl malonate and (E)-(2-nitrovinyl)benzene as model substrates, the Ni/SiO2 modified with chiral diamine affords 93% ee and an apparent turnover frequency of 18.1 h–1, 3.6-fold that of the corresponding chiral Ni complexes. The experimental results demonstrate that the peripheral Ni sites in close contact with SiO2 support are likely to be the active sites, which are distinct from homogenous complexes. The continuous flow production of chiral compounds for more than 65 h was achieved by packing the solid catalysts in a fixed bed reactor with dimethyl malonate and (E)-(2-nitrovinyl)benzene as substrates.

Indication of Pd-C or Cu-C Intermediate in Respective Bimetallic Nanoclusters Pd/Au-PVP or Cu/Au-PVP Catalyzed Oxidations of endo-4-Oxatricyclo[5.2.1.02,6]-8-decene and Tetrahydro-γ-carbolines.

Catalytic oxidations of tricyclic endo-norbornene-fused tetrahydrofuran with bimetallic nanoclusters Cu/Au-PVP and H2O2 or t-BuOOH as an oxidant provided C-H bond oxidation adjacent to the ether function and 4-oxa-tricyclo[5.2.1.0]-8,9-exo-epoxydecane (4), however, oxidation with Pd/Au-PVP took place at the C=C function giving epoxide 4 and oxidative three-bond forming dimeric product, dodecahydro-1,4:6,9-dimethanodibenzofurano[2,3-b:7,8-b']bisoxolane (5). Formation of the latter suggests the involvement of a reactive Pd-C intermediate. Similarly, oxidative C-C bond forming reactions were found in cycloaddition reactions of N2-Boc-1,2,3,4-tetrahydro-γ-carbolines and 2,3-dihydroxybenzoic acid with 2 - 5 mol% Cu/Au-PVP and H2O2 at 25 °C, providing two-bond-forming [4+2] cycloadducts. Under similar reaction conditions, Pd/Au-PVP did not produce the cycloadduct, indicating a need of complexation between Cu with the carboxylic acid group of 2,3-dihydroxybenzoic acid and allylic amine function of γ-carbolines in the cyclization reaction. The reported intermolecular coupling reactions using Pd/Au-PVP or Cu/Au-PVP nanocluster catalysts under oxidative conditions at 25 °C are unprecedented.

Iodine-mediated oxidative N–S bond formation: a facile one-pot synthetic approach to 1,2,4-benzothiadiazine 1,1-dioxides under transition metal-free conditions

Benzothiadiazine 1,1-dioxide derivatives are widely used because of their diverse biological activities and medicinal prospects. In this study, iodine-oxone mediated oxidative N–S bond formation reaction was described. This new and transition-metal-free approach allows for the convenient synthesis of a variety of 1,2,4-benzothiadiazine 1,1-dioxides from readily available urea derivatives under very mild conditions without using expensive reagents and catalysts. Further, this protocol allows for the development of a library of key building blocks with potential medical applications.

Iron- and Ruthenium-Catalyzed C–N Bond Formation Reactions. Reactive Metal Imido/Nitrene Intermediates

Transition-metal-catalyzed direct C–N bond formation via metal nitrenoid (metal imido/nitrene complexes) transfer reactions such as C–H bond amination/amidation and alkene aziridination is a versatile synthetic strategy for the preparation of nitrogen-containing compounds. In this area of development, iron catalysts are appealing in the context of cost, biocompatibility, and environmental sustainability, and iron-catalyzed direct amination reactions have become a complementary approach in the preparation of nitrogen-containing organic compounds with complexity. Reactive iron imido/nitrene species have been widely proposed as the reaction intermediates for direct reactions with C–H and C═C bonds. However, their short lifetimes in solution make the study of these species difficult. In comparison with iron, ruthenium nitrenoids are considerably more stable but yet are reactive enough for amination reactions, leading to reliable surrogates in understanding the reaction mechanism. In this Perspective, the developments in iron and ruthenium complexes supported by macrocyclic or polydentate ligands for the catalytic amination reactions that occur via metal imido/nitrene intermediates are summarized, as well as the mechanisms involved with highlights on the reactive intermediates. Current limitations, challenges, and potential opportunities for future developments are also discussed.

Application of Halogen-Bonding Catalysis for Markovnikov-Type Hydrothiolation of Alkenes

AbstractCarbon–sulfur bond-formation reactions are applied widely in organic synthesis and chemical biology. Hydrothiolation of alkenes provides a direct way to build carbon–sulfur bonds. Most known methods proceed via radical processes and result in anti-Markovnikov-type products. Herein, we demonstrate that I2 catalyzes the hydrothiolation of alkenes and provides Markovnikov-type products in good to excellent yields. Titration studies revealed that thiol was activated by I2 through halogen bonding. This metal-free reaction has advantages such as green and mild conditions, high functionality tolerance, broad substrate scope, and atom economy. Its application was further demonstrated in peptide syntheses.

Ultrafast C-C and C-N bond formation reactions in water microdroplets facilitated by the spontaneous generation of carbocations.

Carbocations are important electrophilic intermediates in organic chemistry, but their formation typically requires harsh conditions such as extremely low pH, elevated temperature, strong oxidants and/or expensive noble-metal catalysts. Herein, we report the spontaneous generation of highly reactive carbocations in water microdroplets by simply spraying a diarylmethanol aqueous solution. The formation of transient carbocations as well as their ultrafast in-droplet transformations through carbocation-involved C-C and C-N bond formation reactions are directly characterized by mass spectrometry. The intriguing formation and stabilization of carbocations are attributed to the super acidity of the positively charged water microdroplets as well as the high electric fields at the water-air interfaces. Without the utilization of external acids as catalysts, we believe that these microdroplet reactions would pose a new and sustainable way for the construction of aryl-substituted compounds.

Ortho-[1-(p-MeOPhenyl)vinyl]benzoate PMPVB as a recyclable auxiliary for C-O and C-S bond formation reactions under Brønsted acid catalysis.

A practically simple and useful method is reported for the synthesis of ethers and thioethers via Brønsted acid-catalyzed activation of ortho-[1-(p-MeOphenyl)vinyl]benzoate (PMPVB) donors derived from alcohols. The mechanism of action is based on the remote activation of an active alkene followed by intramolecular 5-exo-trig cyclization leading to a reactive intermediate that can react via a substrate dependent SN1 or SN2 mechanism with alcohols and thiol nucleophiles providing facile access to ether and thioether functionalities, respectively.

Copper-catalyzed oxidative selective cyclization/C–N cross-coupling of two tryptamines to access 3a-tryptamine-pyrroloindolines

We report the highly selective copper-catalyzed oxidative cyclization/C–N cross-coupling of two tryptamines to access a new molecular indole-linked-pyrroloindoline framework.

Strained cycloalkanols in C–C bond formation reactions: a boon in disguise!

A summary of the various ring opening reactions of strained and unstrained cycloalkanols is elaborated in the present review. Key emphasis on the reactivities pertaining to cyclopropanols, cyclobutanols and higher unstrained analogues is provided.

Transition metal-free [2,3]-sigmatropic rearrangement in the reaction of sulfur ylides with allenoates.

An unprecedented transition metal free [2,3]-sigmatropic rearrangement involving stabilized sulfur ylides and allenoates has been thoroughly established. The scope and utility of this reaction have been extensively studied resulting in C-C bond formation under mild conditions with greater than 20 examples reported. A highlight of the work is the simple and fully operational process that does not involve the use of carbenes or the associated hazardous and sensitive reagents. The reaction can be performed at room temperature and using an open flask. Interestingly, the new C-C bond formation reaction is gram scalable, and the obtained isomers are readily separable, affording interesting building blocks that can be used in the preparation of complex molecules.

Dithiocarbamate-mediated thioamidation of arylglyoxylic acids by decarboxylative–decarbonylative C–C bond formation reactions

Dithiocarbamates are explored in decarboxylative–decarbonylative thioamidation of arylglyoxylic acids in the presence of Pd-catalyst. Cleavage of two C–C bonds and one C–S bond occurs along with the formation of a new C–C bond in a single strategy.

Recent advances in metal directed C-H amidation/amination using sulfonyl azides and phosphoryl azides.

Transition metal-catalyzed C-N bond formation reactions have gained popularity as a method for selectively transforming common C-H bonds into N-functionalized molecules. This approach is particularly useful for synthesizing aminated molecules, which require aminating reagents and amidated building blocks. Over the past two decades, significant advancements have been achieved in transition-metal-catalyzed C-H functionalization, with organic azides emerging as promising amino sources and internal oxidants. This review focuses on recent developments in utilizing sulfonyl and phosphoryl azides as building blocks for directed intra- and intermolecular C-H functionalization reactions. Specifically, it discusses methods for synthesizing sulfonamidates and phosphoramidates using sulfonyl and phosphoryl azides, respectively. The article highlights the potential of C-H functionalization reactions with organic azides for efficiently and sustainably synthesizing N-functionalized molecules, providing valuable insights into the latest advancements in this field.

Ruthenium-catalyzed intermolecular alkene-alkyne couplings in biologically relevant media.

Cationic cyclopentadienyl Ru(ii) catalysts can efficiently promote mild intermolecular alkyne-alkene couplings in aqueous media, even in the presence of different biomolecular components, and in complex media like DMEM. The method can also be used for the derivatization of amino acids and peptides, therefore proposing a new way to label biomolecules with external tags. This C-C bond-forming reaction, based on simple alkene and alkyne reactants, can now be added to the toolbox of bioorthogonal reactions promoted by transition metal catalysts.

Palladium-catalysed deaminative/decarboxylative cross-coupling of organoammonium salts with carboxylic acids.

A palladium-catalysed carbon-carbon bond-forming reaction via deaminative/decarboxylative cross-coupling of organoammonium salts with carboxylic acids was developed. Under the reaction conditions, polyfluoroaromatic carboxylic acids, propiolic acids and α-cyano benzyl carboxylic acid reacted smoothly with benzyl ammonium salts to produce the corresponding carbon-carbon coupling products in good-to-excellent yields.

One-pot, three-component, iron-catalyzed synthesis of benzimidazoles via domino C-N bond formation.

An efficient one-pot, three-component process for the synthesis of benzimidazole derivatives using a catalytic amount of Fe(iii) porphyrin has been developed. The reaction proceeds via domino C-N bond formation and cyclization reactions of benzo-1,2-quinone, aldehydes and ammonium acetate as a nitrogen source to selectively produce benzimidazole. A number of benzimidazole derivatives have been synthesized using this method in high yields under mild reaction conditions.

Bicyclic N-dihalocyclopropylamide derivatives as precursors of nitrogen-containing fused polycyclic systems.

Examples of carbon-carbon bond-forming cyclisation reactions, involving allyl cations generated by the thermal ring-opening of halocyclopropanes, have been scarcely reported. In this contribution, we are describing the results of a study conducted with N-dihalocyclopropylamide substrates, designed as precursors of cyclic iminium intermediates that were aimed at participating in intramolecular reactions with electron-rich aromatic groups. Competitive side-reactions were identified, and access to the desired polycyclic products was carefully evaluated. The results were found to be strongly dependent on the substitution pattern of the nucleophilic aromatic moieties, as well as on the sizes of the rings of the target products. In spite of the rather moderate yields generally obtained, this approach represents a particularly short and inexpensive route to various interesting nitrogen-containing polycyclic systems, namely benzoindolizidine, benzoquinolizidine, piperidinobenzoazepane and azepanoisoquinoline compounds.

Applications of palladium-catalyzed C-N cross-coupling reactions in pharmaceutical compounds.

C-N cross-coupling bond formation reactions have become valuable approaches to synthesizing anilines and their derivatives, known as important chemical compounds. Recent developments in this field have focused on versatile catalysts, simple operation methods, and green reaction conditions. This review article presents an overview of C-N cross-coupling reactions in pharmaceutical compound synthesis reports. Selected examples of N-arylation reactions of various nitrogen-based compounds and aryl halides are defined for preparing pharmaceutical molecules.

Ruthenium-catalysed α-prenylation of ketones using prenol.

Prenol and isoprenoids are common structural motifs in biological systems and possess diverse applications. An unprecedented direct catalytic prenylation of ketones using prenol is attained. This C-C bond formation reaction requires only a ruthenium pincer catalyst and a base, and H2O is the only byproduct.

Recent Progress in the C—S Bond Formation Reactions Mediated by Visible Light

Recent Progress in the C—S Bond Formation Reactions Mediated by Visible Light

Low-cost transition metal catalysed Negishi coupling: an update.

The Negishi coupling is a significant C-C bond-forming reaction to access synthetically valuable organic compounds. In recent years, researchers have developed sustainable first-row transition metal (Fe, Co, Ni and Cu) based complexes in place of the conventional Pd catalyst for this reaction. Several such low-cost metal-based catalysts showed high efficiency and potential application in natural product synthesis. This review focuses on the recent achievements in low-cost transition metal-based Negishi coupling reactions, covering reports from 2016.