Diazo Esters Research Articles

Synthesis of novel reactive disperse dyes comprising α-phenyl diazo ester groups for polyurethane fiber dyeing

A new molecular design of dyes comprising diazo groups was proposed to address the severe staining problem of polyurethane (PU) fibers dyed with disperse dyes. Nine reactive disperse dyes containing α-phenyl diazo ester as the reactive group were designed and synthesized, and their structures were characterized using nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and infrared spectroscopy. The absorption and thermal properties of the nine dyes were also investigated. PU fibers were dyed with these dyes, and the corresponding dyeing and fixing processes were optimized. PU fibers treated using a simple heating process exhibited excellent fixation performance, which was confirmed through studying their fixation, migration, and fastness properties. PU fibers dyed with dyes containing one diazo group exhibited fixation values of 50.6%–75.8%, which were considerably increased to 83.9%–92.9% when dyes with two diazo groups were used. These high fixation values hindered the migration of the dye molecules, effectively reducing their staining on other fibers. Therefore, the dyed PU fibers exhibited excellent color fastnesses to soaping, rubbing, and sublimation. The reaction mechanism between the dye and fiber was proposed based on a model reaction experiment and theoretical analysis. The results indicated that the N–H bond of the PU macromolecule was the main reaction site, on which carbene intermediates reacted with the fiber through an insertion reaction.

Chemoselective and Triggered Decomposition of Diazo Esters by the [(IMes)Rh2(OAc)4] Complex: En Route to Assisted Tandem Catalysis from Mixtures of Diazo Compounds

AbstractDecomposition of aryl and unsubstituted diazo ester into Rh(II)‐carbenes by the [(IMes)Rh2(OAc)4] complex is shown to be slower than with Rh2(OAc)4. Diazo esters substituted by a second electron‐withdrawing group do not suffer nitrogen extrusion when exposed for several hours to this (NHC)Rh(II) complex at room temperature. This chemoselective decomposition of diazo esters depending on their substituent (Ar, H, EWG) can furthermore be achieved on a mixture of substrates. The catalytic activity of [(IMes)Rh2(OAc)4] towards electron‐poor diazo compounds is also restored by heating to reflux in chloroform, or after decomplexation of the NHC by addition of GaCl3. The [(IMes)Rh2(OAc)4] complex was then used to induce a fully selective reaction cascade from a mixture of two diazo esters. First, a donor/acceptor diazo compound was decomposed selectively at room temperature to give an intermolecular O−H insertion product without any decomposition of the electron poor diazo compound. Addition of GaGl3 then triggered nitrogen extrusion from the diazo malonate to give a 1,5‐C−H insertion product. This transformation, where decomposition of diazo compounds catalyzed by Rh(II) complexes can be externally controlled, represents the first example of assisted tandem catalysis with two metal carbene precursors.

Visible-Light-Mediated gem-Difunctionalization of Diazo Compounds with Vinyl Sulfoxonium Ylides and Thiols

AbstractA visible-light-induced multicomponent reaction of vinyl sulfoxonium ylide, thiol, and diazo ester to generate tertiary sulfide is described. The present diastereoselective gem-difunctionalization of the diazo ester can be achieved under mild conditions, as it does not require any additives, catalysts, or transition metals and is tolerant of air and moisture. Due to more nucleophilicity, vinyl sulfoxonium ylide undergoes S–H insertion with thiols to generate an allyl sulfide intermediate. Simultaneously, diazo ester undergoes photolysis to generate a carbene intermediate. Subsequently, the coupling of carbene and allyl sulfide intermediates generates sulfonium ylide, which undergoes Doyle–Kirmse rearrangement to generate tertiary sulfide scaffolds.

Post‐modification of azo dyes using an α‐phenyl diazo ester for improving the colour fixation properties of polyurethane fibre

AbstractColour fastness of polyurethane fibre dyed with conventional disperse dyes is always poor owing to the insufficient affinity between fibres and dyes. Thus, three novel azo dyes containing an α‐phenyl diazo ester moiety were designed in this study. The dyes were synthesised through two‐step post‐modification of a hydroxylated azo benzene chromophore. All three dyes were characterised using proton and carbon nuclear magnetic resonance, high‐resolution mass spectrometry and infrared spectrometry. The ultraviolet‐visible absorption and thermal properties of the dyes were also studied. Fixation properties of these dyes on polyurethane fibre were examined using samples dyed using a non‐aqueous dyeing method. Practicality of these dyes, that is colour depth, fixation value, colour fastness and dye migration degree, was further verified on fibre dyed via an aqueous dyeing method. Finally, the mechanical properties of the dyed polyurethane fibre were explored.

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines.

Herein, we report a visible-light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε-amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this multicomponent reaction protocol.

Synthesis of Difluorocyclopropanes via Visible‐Light‐Mediated [1+2] Cycloaddition of Diazo Esters with gem‐Difluoroalkenes and Evaluation of their Antifungal Activity

AbstractIn this work, we reported a method for construction of difluorocyclopropanes through visible light‐promoted [1+2] cycloaddition reaction of aryl diazo esters with gem‐difluoroalkenes. The reaction proceeds under mild conditions, encompasses a wide range of substrates (36 examples), exhibits good tolerance to various substituents, and demonstrates a diastereoselectivity of >20:1. Additionally, antifungal activity evaluation revealed that these derivatives exhibited certain activity, the EC50 values for the products towards Botrytis cinerea and Rhizoctonia solani were measured to be 1.51 and 1.36 μM, respectively, which are significantly lower than those of commercial fungicides Hymexazol and Azoxystrobin. This work not only provides an efficient method for the synthesis of difluorocyclopropanyl derivatives, but reveals their potential applications in fungicide creation.

Biocatalytic strategy for the construction of sp3-rich polycyclic compounds from directed evolution and computational modelling.

Catalysis with engineered enzymes has provided more efficient routes for the production of active pharmaceutical agents. However, the potential of biocatalysis to assist in early-stage drug discovery campaigns remains largely untapped. In this study, we have developed a biocatalytic strategy for the construction of sp3-rich polycyclic compounds via the intramolecular cyclopropanation of benzothiophenes and related heterocycles. Two carbene transferases with complementary regioisomer selectivity were evolved to catalyse the stereoselective cyclization of benzothiophene substrates bearing diazo ester groups at the C2 or C3 position of the heterocycle. The detailed mechanisms of these reactions were elucidated by a combination of crystallographic and computational analyses. Leveraging these insights, the substrate scope of one of the biocatalysts could be expanded to include previously unreactive substrates, highlighting the value of integrating evolutionary and rational strategies to develop enzymes for new-to-nature transformations. The molecular scaffolds accessed here feature a combination of three-dimensional and stereochemical complexity with 'rule-of-three' properties, which should make them highly valuable for fragment-based drug discovery campaigns.

Catalytic synthesis of β-lactam derivatives by carbonylative cycloaddition of acylsilanes with imines via a palladium Fischer-carbene intermediate

AbstractFischer-type carbene complexes are characterized by the presence of a π-donating group, such as an alkoxy group on the carbene carbon. Despite the notable progress that has been made in synthetic methods that involve the use of Fischer-type carbene complexes, stoichiometric amounts of carbene complexes are still required for such reactions and catalytic variants remain elusive. This limitation primarily stems from the lack of suitable carbene precursors, which is in sharp contrast to the fact that carbene complexes bearing an electron-withdrawing group can be readily generated from the corresponding diazo esters. Here we report that acylsilanes can function as a precursor for a Fischer-carbene complex by the action of a palladium catalyst. This system can be used in catalytic carbonylative cycloaddition reactions with imines to form densely substituted β-lactam derivatives. A key siloxycarbene–palladium intermediate complex was isolated and successfully characterized by X-ray crystallography.

Carbene-mediated stereoselective olefination of vinyl sulfoxonium ylides with diazo compounds and acetals.

The development of stereoselective olefination using sulfur ylide-derived vinyl carbenes with diazo esters and acetals is reported. Both reactions proceed through nucleophilic addition to electrophiles at the γ-position of an in situ-generated 2-alkoxy furan intermediate. The synthetic utility of the developed method is demonstrated by the total synthesis of rubrolide E. Detailed mechanistic investigations and quantum chemical calculations provide insight into the reaction mechanism.

A copper-catalyzed annulation reaction of diazo esters with propargyl amines for the synthesis of 2,5-dihydropyrroles

An efficient protocol for the synthesis of 2,5-dihydropyrroles using diazo esters and propargyl amines has been reported, featuring mild reaction conditions, straightforward operation, the absence of metal ligands, and high atom economy.

Eco-friendly anaerobic oxidation of aryl diazo esters with heterocyclic N-oxide under ball milling: Synthesis of 1,2-dicarbonyl systems

Herein we report anaerobic oxidation of metal carbenoids generated from aryl diazo esters under ball milling, with heterocyclic N-oxide in presence of catalytic copper(I) to afford 1,2-dicarbonyls in excellent yield....

Au(I) and HOTf‐Catalyzed Cascade [5+1]‐Annulations between Allenylacetals and Diazo Esters To Form 1,3‐ and 2,3‐Disubstituted Naphthoates, Respectively

AbstractGold‐catalyzed [5+1]‐annulations between allenylacetals with diazo esters to form 1,3‐disubstituted naphthoate derivatives are described. Notably, this reaction chemoselectivity is switched to 2,3‐naphthoate products when using the HOTf catalyst. Mechanistic studies of these reactions support an acetal activation, in which oxoniums are formed initially, followed by attack of the allene, generating allyl cations to trap α‐diazo esters. In gold catalysis, such diazo addition intermediates undergo Roskamp rearrangement, whereas in HOTf catalysis the same intermediates undergo a Conia‐ene reaction instead.

Rh-Catalyzed C–H Functionalization of the (Pyrazol-5-yl)pyridine Core of GBT-440

AbstractThe Rh-catalyzed cross dehydrogenative coupling (CDC)/alkylation of the pyrazolylpyridine unit of GBT-440 proceeded smoothly under ambient conditions and selectively on the pyrazole unit while directed by the pyridine. The scope of these reactions was established by employing simple as well as conjugated olefins for CDC and various diazo esters and the TIPS-EBX reagent for alkylation. At the outset, a focused small molecule library around the bis-heterocyclic core of GBT-440 was developed via C–H functionalization.

Pd-Catalyzed Regioselective Cyclopropanation of 2-Substituted 1,3-Dienes.

A Pd-catalyzed 3,4-regioselective cyclopropanation of 2-substituted 1,3-dienes by decomposition of diazo esters is reported. The vinylcyclopropanes generated are isolated in practical chemical yields with high levels of regioselectivity but low diastereoselectivity. The system operates under mild reaction conditions, is scalable, and tolerates various sensitive functional groups. A series of original postcatalytic derivatizations is presented to highlight the synthetic potential of the catalytic method.

Copper‐Catalyzed Olefinic C(sp2)−H Activation/Carbene Insertion/Ester Hydrolysis/Cyclization with Aryl Diazo Esters for the Synthesis of Multisubstituted Furanones

AbstractA copper‐catalyzed olefinic C(sp2)−H activation/carbene insertion/ester hydrolysis/cyclization sequence has been developed for the synthesis of substituted 2(5H)‐furanones employing readily available enaminones and aryl diazo esters as substrates. This method features operationally simple and good functional group tolerance. The transformation could be scaled up to gram quantities and the obtained 2(5H)‐furanone derivatives could be easily converted to a wide range of useful synthetic building blocks, indicative of the applicability of the synthetic strategy. Isotope labeling experiments demonstrated the ester group of diazo esters was hydrolyzed during the reaction.

Fast UV‐ and Visible Light Induced Polymer Network Formation Using Carbene Mediated CH‐insertion Based Crosslinking (CHic) Via Nitrophenyl Diazo Esters

AbstractThe synthesis and characterization of highly photosensitive coatings containing a diazo‐based crosslinker that exhibits high photoreactivity in the near‐visible UV and toward sunlight is present. Nitrophenyl diazo ester (nitroPEDAz) moieties are incorporated into polymer chains via free radical polymerization and generate upon irradiation carbenes, which undergo a CH insertion‐based crosslinking (CHic) reaction. The copolymers are deposited onto substrate surfaces through known coating techniques and then activated to form polymer networks and simultaneously attach covalently to the surfaces if CH groups are available. It is demonstrated that very low light doses on the order of 20 mJ cm−2 are sufficient to generate surface‐attached networks and that the copolymer can be patterned photolithographically into defined structures on a broad spectrum of substrates using UV‐ and natural sunlight. Even a few seconds of sunlight exposure are sufficient to crosslink and surface‐attach the film.

Complete integration of carbene-transfer chemistry into biosynthesis.

Biosynthesis is an environmentally benign and renewable approach that can be used to produce a broad range of natural and, in some cases, new-to-nature products. However, biology lacks many of the reactions that are available to synthetic chemists, resulting in a narrower scope of accessible products when using biosynthesis rather than synthetic chemistry. A prime example of such chemistry is carbene-transfer reactions1. Although it was recently shown that carbene-transfer reactions can be performed in a cell and used for biosynthesis2,3, carbene donors and unnatural cofactors needed to be added exogenously and transported into cells to effect the desired reactions, precluding cost-effective scale-up of the biosynthesis process with these reactions. Here we report the access to a diazo ester carbene precursor by cellular metabolism and a microbial platform for introducing unnatural carbene-transfer reactions into biosynthesis. The α-diazoester azaserine was produced by expressing a biosynthetic gene cluster in Streptomyces albus. The intracellularly produced azaserine was used as a carbene donor to cyclopropanate another intracellularly produced molecule-styrene. The reaction was catalysed by engineered P450 mutants containing a native cofactor with excellent diastereoselectivity and a moderate yield. Our study establishes a scalable, microbial platform for conducting intracellular abiological carbene-transfer reactions to functionalize a range of natural and new-to-nature products and expands the scope of organic products that can be produced by cellular metabolism.

B(C6F5)3-Catalyzed Diastereoselective and Divergent Reactions of Vinyldiazo Esters with Nitrones: Synthesis of Highly Functionalized Diazo Compounds.

Herein we report a mild, transition-metal-free, highly diastereoselective Lewis acid catalyzed methodology toward the synthesis of isoxazolidine-based diazo compounds from the reaction between vinyldiazo esters and nitrones. Interestingly, the isoxazolidine products were identified to have contrasting diastereoselectivity to previously reported metal-catalyzed reactions. Furthermore, the same catalyst can be used with enol diazo esters, prompting the formation of Mukaiyama-Mannich products. These diazo products can then be further functionalized to afford benzo[b]azepine and pyrrolidinone derivatives.

Visible-light-promoted N-H functionalization of O-substituted hydroxamic acid with diazo esters.

Herein we report an N-H functionalization of O-substituted hydroxamic acid with diazo esters under blue LED irradiation conditions. The present transformations could be performed efficiently under mild conditions without use of catalyst, additive and N2 atmosphere. Interestingly, when THF and 1,4-dioxane were employed as the reaction solvents, an active oxonium ylide involved three-component reaction and an N-H insertion of carbene species into hydroxamate occurred, respectively.