Single Bond Cleavage Research Articles

Sodium-Mediated Reductive C-C Bond Cleavage Assisted by Boryl Groups.

In contrast to the well-established oxidative C=C double bond cleavage to give the corresponding carbonyl compounds, little is known about reductive C=C double bond cleavage. Here we report that C-C single bond cleavage in 1,2-diaryl-1,2-diborylethanes proceeds by reduction with sodium metal to yield α-boryl benzylsodium species. In combination with our previous reductive diboration of stilbenes, the overall transformation represents reductive cleavage of the C=C double bonds of stilbene to yield α-boryl-α-sodiated toluenes. This reductive two-step C=C double bond cleavage is applicable to ring-opening or ring-expansion reactions of polycyclic aromatic hydrocarbons.

Zirconium and hafnium catalyzed C–C single bond hydroboration

Selective cleavage and subsequent functionalization of C−C single bonds present a fundamental challenge in synthetic organic chemistry. Traditionally, the activation of C−C single bonds has been achieved using stoichiometric transition-metal complexes. Recently, examples of catalytic processes were developed in which use is made of precious metals. However, the use of inexpensive and Earth-abundant group IV metals for catalytic C−C single-bond cleavage is largely underdeveloped. Herein, the zirconium-catalyzed C−C single-bond cleavage and subsequent hydroboration reactions is realized using Cp2ZrCl2 as a catalytic system. A series of structures of various γ-boronated amines are readily obtained, which are otherwise difficult to obtain. Mechanistic studies disclose the formation of a N–ZrIV species, and then a β-carbon elimination route is responsible for C–C single bond activation. Besides zirconium, hafnium exhibits a similar performance for this transformation.

Pyrolysis experiments of model compounds to explore carbon isotope fractionation in propane from natural gas

Investigating the mechanisms that determine the bulk and position-specific carbon isotopic distributions of propane in natural gas will help elucidate its formation and evolution. We used octadecane and squalane as model compounds that give simple precursors for gas production in gold-tube isothermal pyrolysis experiments to study the variations in intermolecular and intramolecular distributions of isotopes in the generated gaseous hydrocarbons. The δ13C values of the products and inverses of their carbon numbers (1/n where n = C1–C5) showed a negative linear relationship versus maturity, indicating that they formed by homolytic cleavage of C–C bonds and that the precursors showed homogeneous distributions of carbon isotopes. However, the significant difference in the kinetic isotopic effects (KIEs) of the gas generated by cracking of two model compounds under the same experimental conditions is not readily explained by single homolytic bond cleavage. The results indicate that besides the KIE of C–C bond cleavage, the bulk and position-specific carbon isotopic compositions of propane are related to the chemical and isotopic structures of the precursors and the propane transformation ratio. Based on the sites of C–C bond cleavage, two isotopic fractionation patterns (i.e., normal propyl and isopropyl models) may explain the bulk and position-specific carbon isotopic distributions of the generated propane. According to the propyl model, propane originates from (normal) propyl structures (CH3CH2CH2*) in the precursor via C–C bond cleavage at a terminal site of a propyl group, while the isopropyl model involves propane derived from isopropyl structures (CH3CH*CH3) in the precursor, with C–C bond cleavage at the central site. Simulations show that these distributions for propane cracked from octadecane closely follow the propyl model, whereas propane generated from squalane showed mixed contributions from both models, and its bulk and position-specific carbon isotopic distributions depend on the proportions of propyl and isopropyl structures in the precursors. Variations of propane’s position-specific carbon isotopic distributions during the main stage of propane generation indicate that free radical reactions are the main pathway for thermogenic propane formation, resulting in similar KIEs for propane terminal and central carbons. Therefore, the position-specific carbon isotopic distribution of propane can provide evidence of its formation mechanism and shows potential for revealing the origin and evolution of natural gas.

Visible light photoflow synthesis of a Cu(ii) single-chain polymer nanoparticle catalyst.

We herein pioneer the visible light (λ max = 410 nm) mediated flow synthesis of catalytically active single-chain nanoparticles (SCNPs). Our design approach is based on a copolymer of poly(ethylene glycol) methyl ether methacrylate and a photocleavable 2-((((2-nitrobenzyl)oxy)carbonyl)amino)ethyl methacrylate monomer which can liberate amine groups upon visible light irradiation, allowing for single-chain collapse via the complexation of Cu(ii) ions. We initially demonstrate the successful applicability of our design approach for the batch photochemical synthesis of Cu(ii) SCNPs and transfer the concept to photoflow conditions, enabling, for the first time, the continuous production of functional SCNPs. Critically, we explore their ability to function as a photocatalyst for the cleavage of carbon-carbon single and double bonds on the examples of xanthene-9-carboxylic acid and oleic acid, demonstrating the advantageous effect SCNPs can provide over analogous small molecule catalysts.

Dithiocarbamate mediated thioamidation via C–C single bond cleavage of styrene: study of the protocol in decarbonylative and decarboxylative thioamidations

Styrene undergoes transition-metal-free dealkenylative thioamidations by dithiocarbamate anions under aerial conditions. Decarbonylative and decarboxylative thioamidations have also been tested on benzaldehyde, toluene and benzoic acid.

Methylene Insertion into Nitrogen-Heteroatom Single Bonds of 1,2-Azoles via a Zinc Carbenoid: An Alternative Tool for Skeletal Editing.

The nitrogen-heteroatom single bonds of 1,2-azoles and isoxazolines underwent methylene insertion in the presence of CH2 I2 (6 equiv.) and diethylzinc (3 equiv.) to produce a wide variety of the ring-expanded six-membered heterocycles. Density functional theory calculations suggest that the methylene insertion proceeds via cleavage of nitrogen-heteroatom single bonds followed by ring closure.

Deconstructive Cyanomethylation Enabled by Radical Cross‐Coupling through Multiple C−C Bond and C−H Bond Cleavage

AbstractBeing in its infancy, radical cross‐coupling is highly efficient for C−C bond construction, though suffers from selectivity problems and limited reaction types. New methodologies to realize radical cross‐coupling selectively are highly desired. Herein, an iron catalyzed deconstructive cyanomethylation of unstrained cyclic and linear alcohols with acetonitrile has been developed through radical cross‐coupling. The unprecedented method enables a ring‐opening functionalization of cyclohexanols to produce α‐cyanomethyl ketones. Notably, the highly challenging reaction involves twice C−C single bond cleavage through β‐scission of alkoxyl radical intermediates, and twice C(sp3)−H bond transformation via hydrogen atom transfer (HAT) procedures, resulting in two carbon radical species that realize a radical cross‐coupling process to form a new C(sp3)−C(sp3) bond selectively. α‐arylketo and α‐aryl substituted tertiary alcohols can also be applied as substrates, leading to terminal cyano‐functionalized linear products, with ketone as the leaving fragment. Mechanistically, a new procedure to generate alkoxyl radical with chlorine radical through the in‐situ formed intermediate cycloalkyl hypochlorite was suggested.magnified image

Photoinduced Radical Cyclization of 1,6‐Diynes: Rapid Access to Highly Substituted Carbocyclic and Heterocyclic Compounds

AbstractWe have developed photoinduced sulfonyl radical‐triggered cyclization of 1,6‐dynes without metals, oxidants, or additives. During the reaction, three new bonds are formed (−SO2−C, C−C, and C−I/C−Se−) under mild conditions, with excellent selectivity. The conversion is temporally and atomically economical and is easy to handle even on a gram scale. Detailed mechanistic studies showed that the reaction proceeds via a radical pathway. Subsequent synthetic transformations of the new products produced various substituted compounds. Importantly, we observed an unprecedented and selective C−C single bond cleavage with boronic acid insertion under Suzuki reaction conditions.magnified image

Selective photocatalytic removal of sulfonamide antibiotics: The performance differences in molecularly imprinted TiO2 synthesized using four template molecules

Four types of molecularly imprinted TiO2 photocatalysts named MIP-TiO2/sulfadiazine (SD), MIP-TiO2/sulfamethoxazole (SMX), MIP-TiO2/sulfonamide (SN) and MIP-TiO2/aniline (AN), were synthesized. The five catalysts exhibited different degrees of selectivity for two types of sulfonamide antibiotics (SAs), SD and SMX. In the systems of NIP–TiO2, MIP-TiO2/SD, MIP-TiO2/SMX, MIP-TiO2/SN and MIP-TiO2/AN, the degradation rate constants of SD were 0.0789, 0.1031, 0.0859, 0.1034 and 0.1051 min−1, respectively. Moreover, the removal rate constants of SMX on the mentioned catalysts were 0.1076, 0.3250, 0.4260, 0.3885 and 0.5848 min−1, correspondingly. The single bond cleavage (C–S, C–N, and S–N bonds), hydroxylation, ring-opening, oxidation, and deamination were the major transformation pathways of SAs. With the presence of MIP-TiO2/SN and MIP-TiO2/AN, more low molecular weight products were generated, and the intermediates preferred to go through further hydroxylation and oxidation reactions. Therefore, besides MIP-TiO2/SD and MIP-TiO2/SMX, the novel MIP-TiO2/SN and MIP-TiO2/AN, which were prepared by using substances with the similar main functional groups as SAs as template molecules, had excellent catalytic abilities and less byproducts formed in the situation. The results may provide an effective idea to level up the SAs degradation rates, control the generation of intermediates, and reduce environmental risks.

Rhodium-catalyzed aerobic conversion of 2-diazo-1,3-dicarbonyls to vicinal tricarbonyl compounds and their in-situ stability toward oxidative degradation

Several types of 2-diazo-1,3-dicarbonyl compounds (3), including α-diazo-β-ketoesters, 2-diazo-1,3-diketones and diazomalonates, are converted into the corresponding vicinal tricarbonyls (VTCs) (4) upon exposure to Rh2(OAc)4 catalyst and oxygen gas. The transformation is proposed to occur through the aerobic oxygenation of the rhodium carbenoid intermediate, facilitated by the suppression of a Wolff rearrangement via weak interaction with the substrate carbonyl group (ROC=O or RC=O). The reactions of α-diazo-β-ketoesters and 2-diazo-1,3-diketones give the desirable α,β-diketoesters and vic-triketones in 27-78% isolated yields, along with carboxylic acids and/or 2-oxoacids generated by in-situ oxidative C-C single bond cleavage of the former products. Moreover, the bond cleavage process is completely inhibited when the reactions are performed with diazomalonates, leading to the good to excellent formation of oxomalonates (up to 92% yield).

Metal-Free Catalysis in C-C Single-Bond Cleavage: Achievements and Prospects.

This review article emphasizes the C-C bond cleavage in organic synthesis via metal-free approach. Conventional organic synthesis mainly deals with the reactive π bonds and polar σ bonds. In contrast, the ubiquitous C-C single bonds are inherently stable and are less reactive, which poses a challenge to synthetic chemists. Although inert, such C-C single-bond cleavage reactions have gained attention amongst synthetic chemists, as they provide unique and more straightforward routes, with significantly fewer steps. Several review articles have been reported regarding the activation and cleavage of C-C bonds using different transition metals. However, given the high cost and toxicity of many of these metals, the development of strategies under metal-free conditions is of utmost importance. Though many research articles have been published in this area, no review article has been reported so far. Herein, we discuss the reactions in a more concise way from the year 2012 to today, with emphasis on important reactions. Mechanisms of all the reactions are also well addressed. We believe that this review will be beneficial for the readers who work in this field.

Iron-catalyzed deconstructive alkylation through chlorine radical induced C-C single bond cleavage under visible light.

Selective C-C single bond cleavage of simple compounds is a highly challenging and desired process. Herein, a chlorine radical-induced deconstructive C-C bond alkylation with alcohols and alkenes catalyzed by iron salts was reported for the first time. Readily available alcohols and various electron-deficient alkenes were tolerated. Late-stage and large-scale reactions proceed smoothly. This catalyst system shows potential for diversified deconstructive functionalization of simple C-C bonds.

C=C Bond Oxidative Cleavage of BODIPY Photocages by Visible Light.

Photocages for protection and the controlled release of bioactive compounds have been widely investigated. However, the vast majority of these photocages employ the cleavage of single bonds and high-energy ultraviolet light. The construction of a photoactivation system that uses visible light to cleave unsaturated bonds still remains a challenge. Herein, we report a regioselective oxidative cleavage of C=C bonds from a boron-dipyrrolemethene (BODIPY)-based photocage by illumination at 630 nm, resulting in a free aldehyde and a thiol fluorescent probe. This strategy was demonstrated in live HeLa cells, and the generated α-formyl-BODIPY allowed real-time monitoring of aldehyde release in the cells. In particular, it is shown that a mannose-functionalized photocage can target HepG2 cells.

Pd-Catalyzed tandem C–C/C–O/C–H single bond cleavage of 3-allyloxybenzocyclobutenols

A Pd-catalyzed skeletal rearrangement of 3-allyloxybenzocyclobutenols was achieved, which involved tandem C–C/C–O bond cleavage and C–H allylic substitution.

Transition Metal-Mediated C-C Single Bond Cleavage: Making the Cut in Total Synthesis.

Transition-metal-mediated cleavage of C-C single bonds can enable entirely new retrosynthetic disconnections in the total synthesis of natural products. Given that C-C bond cleavage inherently alters the carbon framework of a compound, and that, under transition-metal catalysis, the generated organometallic or radical intermediate is primed for further complexity-building reactivity, C-C bond-cleavage events have the potential to drastically and rapidly remodel skeletal frameworks. The recent acceleration of the use of transition-metal-mediated cleavage of C-C single bonds in total synthesis can be ascribed to a communal recognition of this fact. In this Review, we highlight ten selected total syntheses from 2014 to 2019 that illustrate how transition-metal-mediated cleavage of C-C single bonds at either the core or the periphery of synthetic intermediates can streamline synthetic efforts.

Selective Carbon-Carbon Bond Cleavage of Cyclopropylamine Derivatives.

This review summarizes synthetic developments reported from 1987 to 2019 that exploit C-C single bond cleavage of cyclopropylamine-based systems. The synthetic and mechanistic aspects of key methodologies are highlighted, and examples where aminocyclopropanes are exploited as key intermediates in multistep synthesis are also discussed. The review encompasses cases where aminocyclopropanes participate in polar reactions, pericyclic processes, radical-based reactions, and C-C bond activations.

Field Induced Fragmentation (Fif) Spectra of Oxygen Containing Volatile Organic Compounds with Reactive Stage Tandem Ion Mobility Spectrometry and Functional Group Classification by Neural Network Analysis.

Mobility isolated spectra were obtained for protonated monomers of 42 volatile oxygen containing organic compounds at ambient pressure using a tandem ion mobility spectrometer with a reactive stage between drift regions. Fragment ions of protonated monomers of alcohols, acetates, aldehydes, ketones, and ethers were produced in the reactive stage using a 3.3 MHz symmetrical sinusoidal waveform with an amplitude of 1.4 kV and mobility analyzed in a 19 mm long drift region. The resultant field induced fragmentation (FIF) spectra included residual intensities for protonated monomers and fragment ions with characteristic drift times and peak intensities, associated with ion mass and chemical class. High efficiency of fragmentation was observed with single bond cleavage of alcohols and in six-member ring rearrangements of acetates. Fragmentation was not observed, or seen weakly, with aldehydes, ethers, and ketones due to their strained four-member ring transition states. Neural networks were trained to categorize spectra by chemical class and tested with FIF spectra of both familiar and unfamiliar compounds. Rates of categorization were class dependent with best performance for alcohols and acetates, moderate performance for ketones, and worst performance for ethers and aldehydes. Trends in the rates of categorization within a chemical family can be understood as steric influences on the energy of activation for ion fragmentation. Electric fields greater than 129 Td or new designs of reactive stages with improved efficiency of fragmentation will be needed to extend the practice of reactive stage tandem IMS to an expanded selection of volatile organic compounds.

Selective Dealkenylative Functionalization of Styrenes via C-C Bond Cleavage

As a readily available feedstock, styrene with about 25 million tons of global annual production serves as an important building block and organic synthon for the synthesis of fine chemicals, polystyrene plastics, and elastomers. Thus, in the past decades, many direct transformations of this costless styrene feedstock were disclosed for the preparation of high-value chemicals, which to date, generally performed on the functionalization of styrenes through the allylic C-H bond, C(sp2)-H bond, or the C=C double bond cleavage. However, the dealkenylative functionalization of styrenes via the direct C-C single bond cleavage is so far challenging and still unknown. Herein, we report the novel and efficient C-C amination and hydroxylation reactions of styrenes for the synthesis of valuable aryl amines and phenols via the site-selective C(Ar)-C(alkenyl) single bond cleavage. This chemistry unlocks the new transformation and application of the styrene feedstock and provides an efficient protocol for the late-stage modification of substituted styrenes with the site-directed dealkenylative amination and hydroxylation.

Deconstructive Functionalization of Ketones via an LMCT-Promoted C–C Cleavage

In this issue of Chem, Zuo and coworkers report an exciting new strategy for the deconstructive functionalization of ketones. Through merging Lewis-acid-catalyzed nucleophilic 1,2-addition and ligand-to-metal charge transfer (LMCT)-promoted C–C cleavage, common strained and unstrained ketones are transformed into synthetically valuable scaffolds with high efficiency under mild conditions.

Selective C-C Bond Scission of Ketones via Visible-Light-Mediated Cerium Catalysis

Summary Here, we report a general catalytic manifold for the selective C–C bond scission of ketones via the exploitation of the ligand-to-metal charge transfer (LMCT) excitation mode. Through a cooperative utilization of Lewis acid catalysis and LMCT catalysis, the C–C bond of ketones could be selectively and effectively cleaved, enabling the installation of different functionalities at each carbon of the cleaved C–C bond through a sequential and orthogonal manner. This reaction manifold serves as a photocatalytic alternative to the Norrish type I reaction with the combination of visible light and inexpensive cerium salts. Under operationally simple conditions, a wide range of acyclic and cyclic ketones, from simple strained cyclobutanones to complex androsterone with less strained cyclopentanone moiety, could be successfully transformed into versatile chemical building blocks.