Ene Reaction Research Articles

Elucidation of a Dearomatization Route in the Biosynthesis of Oxysporidinone Involving a TenA-like Cytochrome P450 Enzyme.

Oxidative dearomatization of phenols is an important transformation for synthesis of complex molecules. Oxysporidinone and related 2-pyridones are featured with a hydroxy-substituted cyclohexanone ring, which is proposed from dearomatization of phenol. However, detailed biochemical characterization of this process is still undiscovered. Herein, we identified oxysporidinone biosynthetic gene cluster in Fusarium oxysporum by regulator activation and gene knockout study. Through in vivo and in vitro study, we confirmed that the phenol dearomatization process involves two enzymes. OsdM, as a TenA-like cytochrome P450 expected with ring-expansion activity, converts the phenol ring and the 4-hydroxy-2-pyridone core into an unexpected fused [6-5-6] ring system. OsdN, on the other hand, catalyses two successive ene-reductions, which is followed by hydroxylation via OsdM. This new route enriches current knowledge on enzymatic phenol dearomatization and TenA-like P450s mechanism.

Elucidation of a Dearomatization Route in the Biosynthesis of Oxysporidinone Involving a TenA‐like Cytochrome P450 Enzyme

AbstractOxidative dearomatization of phenols is an important transformation for synthesis of complex molecules. Oxysporidinone and related 2‐pyridones feature a hydroxy‐substituted cyclohexanone ring, which has been proposed to form by phenol dearomatization, although the details of the biochemical process are still unknown. In this study, we identified the oxysporidinone biosynthetic gene cluster in Fusarium oxysporum by regulator activation and gene knockout studies. Through in vivo and in vitro studies, we confirmed that the phenol dearomatization process involves two enzymes. OsdM, a TenA‐like cytochrome P450 with expected ring‐expansion activity, converts the phenol ring and the 4‐hydroxy‐2‐pyridone core into an unexpected fused [6‐5‐6] ring system. OsdN, on the other hand, catalyzes two successive ene reduction reactions, followed by hydroxylation by OsdM. This new route enriches current knowledge on enzymatic phenol dearomatization and the mechanism of TenA‐like P450s.

Intermolecular Dearomative 1,2-Amination/Carbonylation via Nucleophilic Addition of Simple Amines to Arene π-Bonds.

The incorporation of the privileged amino functionality is of paramount importance in organic synthesis. In contrast to the well-developed amination methods for alkenes, the dearomative amination of arenes is largely underexplored due to the inherently inert reactivity of arene π-bonds and selectivity challenges. Herein, we report an intermolecular dearomative aminofunctionalization via direct nucleophilic addition of simple amines to chromium-bound arenes. This multicomponent 1,2-amination/carbonylation reaction enables rapid access to complicated alicyclic compounds containing amino and amide functionalities from benzene derivatives under CO-gas-free conditions, which also represents the first application of nitrogen-based nucleophiles in η6-coordination-induced arene dearomatizations.

Lysine-Based Silicone Surfactants

Highly efficient silicone surfactants are typically based on polyether hydrophiles. As part of a program to increase the natural content of silicones, we describe the synthesis of silicone surfactants with amino acid hydrophiles (cysteine, arginine, and lysine). The compounds were prepared using a radial thiol–ene reaction with vinylsilicones for cysteine derivatives and a catalyst-free aza-Michael reaction with arginine and lysine. Short chain surfactants with silicone monomer:hydrophile ratios of 5:1 or less (e.g., telechelic silicones of lysine-linker-(Me2OSi)n-linker-lysine n = 10) were ineffective at stabilizing emulsions of silicone oil (D4): water. However, excellent surfactants were realized as the chain length (n) increased to 25 or 50, stabilizing water-in-oil emulsions with high water content (80% or 90%). The surfactants, especially the longer chain compounds, were stable against pH except <4 or >9 and survived freeze/thaw cycles. These surfactants contain 12–25% natural materials, improving their sustainability compared to those containing synthetic hydrophiles.

Synthesis of aromatic carbamate via palladium catalyzed reductive carbonylation reaction of Nitro benzene: An alternative approach with different nucleophiles other than MeOH

The reactivity of palladium complex supported by phenanthroline ligand has been studied in the reductive carbonylation of PhNO2 using different solvents. Nucleophiles like, 2,4,6- trimethyl phenol (TMP) and 2,2,2-trifluoro ethanol (TFE) were employed to obtain a carbamate that is more readily pyrolyzed, these nucleophiles were selected based on their larger size. TMP as the nucleophilic reagent and toluene as solvent resulted optimum conversion of nitrobenzene with excellent selectivity for carbamate. On the other hand, the use of p-toluene sulfonic acid was confirmed to be effective for the Pd/phenanthroline catalyzed nitrobenzene carbonylation reactions, even when co-solvents are present or other nucleophiles other than MeOH are employed, producing the corresponding carbamate in high selectivity.

Palladium Nanoparticle-Decorated Porous Metal-Organic-Framework (Zr)@Guanidine: Novel Efficient Catalyst in Cross-Coupling (Suzuki, Heck, and Sonogashira) Reactions and Carbonylative Sonogashira under Mild Conditions.

A novel heterogeneous Zr-based metal-organic framework containing an amino group functionalized with nitrogen-rich organic ligand (guanidine), through a step-by-step post synthesis modification approach, was successfully modified by the stabilization of palladium metal nanoparticles on the prepared UiO-66-NH2 support in order to synthesize the Suzuki-Murray, Mizoroki-Heck, and copper-free Sonogashira reactions and also the carbonylative Sonogashira reaction incorporating H2O as a green solvent under mild conditions. This newly synthesized highly efficient and reusable UiO-66-NH2@cyanuric chloride@guanidine/Pd-NPs reported catalyst has been utilized to increase anchoring palladium onto the substrate with the aim of altering the construction of the intended synthesis catalyst to form the C-C coupling derivatives. Several strategies, including X-ray diffraction, Fourier transform infrared, scanning electron microscopy, Brunauer-Emmett-Teller, transmission microscopy electron, thermogravimetric analysis, inductively coupled plasma, energy-dispersive X-ray, and elemental mapping analyzes, were used to indicate the successful preparation of the UiO-66-NH2@cyanuric chloride@guanidine/Pd-NPs. In these reactions, the UiO-66-NH2-supported Pd-NPs illustrated superior performances compared to their catalyst, revealing the benefits of providing nanocatalysts. As a result, the proposed catalyst is favorable in a green solvent, and also, the outputs are accomplished with good to excellent outputs. Furthermore, the suggested catalyst represented very good reusability with no remarkable loss in activity up nine sequential runs.

Light-Mediated Synthesis of Aliphatic Anhydrides by Cu-Catalyzed Carbonylation of Alkyl Halides

Acid anhydrides are valuable in the chemical industry for their role in synthesizing polymers, pharmaceuticals, and other commodities, but their syntheses often involve multiple steps with precious metal catalysts. The simplest anhydride, acetic anhydride, is currently produced by two Rh-catalyzed carbonylation reactions on a bulk scale for its use in synthesizing products ranging from aspirin to cellulose acetate. Here, we report a light-mediated, Cu-catalyzed process for producing aliphatic, symmetric acid anhydrides directly by carbonylation of alkyl (pseudo)halides in a single step without any precious metal additives. The transformation requires only simple Cu salts and abundant bases to generate a heterogeneous Cu0 photocatalyst in situ, maintains high efficiency and selectivity upon scale-up, and operates by a radical mechanism with several beneficial features. This discovery will enable the engineering of bulk processes for producing commodity anhydrides efficiently and sustainably.

Shaping of Pd@UiO-66-biguanidine MOFs into composite beads with Cu-based CMC for synergistic catalysis towards CO-free carbonylative Sonogashira reaction

Integrating fine metal-organic framework (MOF) crystals within various materials to obtain configurable shapes with desired size and mechanical stability is an essential prerequisite for their potential applications on a large scale. In this work, a novel composite bead (Pd@UG/Cu@CMC), composed of Zr-based UiO-66-biguanidine-supported Pd MOFs (Pd@UG) embedded in the three-dimensional (3D) networks of Cu2+ crosslinked carboxymethylcellulose (Cu@CMC), has been successfully fabricated using a simple and straightforward metal ion crosslinking technology. The architecture of Pd@UG/Cu@CMC composite beads has been analyzed in detail using inductively coupled plasma atomic emission spectrometry (ICP-AES), Brunner−Emmet−Teller (BET) surface area analysis, Fourier transform infrared (FTIR) spectra, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), elemental mapping, thermogravimetric analysis (TGA), derivative thermogravimetric analysis (DTG) tools. To validate the catalytic aptitude, the as-obtained Pd@UG/Cu@CMC beads were subsequently applied to carbonylative Sonogashira reactions using phenyl formate as a CO surrogate. The results showed that the catalyst had excellent catalytic performance over a broad scope of substrates under mild conditions and produced the desired products in moderate to excellent yields. The presence of Pd and Cu elements in the composite beads is essential, and the Cu played a dual role as both a crosslinker and co-catalyst in these reactions. The synergetic effect between Pd and Cu was conclusively evidenced by comparing them with Pd@UG, Cu@CMC, and their mixture, respectively. The composite beads retained their structure after seven consecutive runs with approximately 11% loss of catalytic efficiency. This work offers a promising route to shaping MOFs and provides suggestive insights for developing novel reusable bimetallic catalysts for high-performance synergistic catalysis.

Mechanism of Cycloisomerization of 15‐Membered Triazaenediynes Macrocycle: A DFT Study

AbstractDFT calculations at M062X/6‐31+G(d,p) and M062X/Def2SVP levels of theory were utilized to explore the mechanism and cycloisomerization of 15‐membered triazaenediyne macrocycles in gas phase and Toluene. Trans triazaenediyne conducted concerted reactions to produce a trans diastereoselective tetracyclic fused structure passing through key cascade reactions starting by an Ene reaction that produced an allene intermediate (ΔG#=37.37 kcal/mol), and following a Diels‐Alder reaction which converted to trans‐tetracyclic ring overcoming a 34.10 kcal/mol barrier. In catalytic Rh (I), two steps reactions converted reagent to a diastereoselective trans‐cyclohexadiene tetracyclic by vanquishing barriers of 30.75 and 22.66 kcal/mol.

THIOSULFINATE-DERIVED THIOALDEHYDES AS ENOPHILES FOR MODIFICATION AND VULCANIZATION OF CIS-1,4-POLYISOPRENE VIA ALDER-ENE REACTIONS

ABSTRACT Thioaldehydes are explored as enophiles in Alder-ene reactions for modification and crosslinking of cis-1,4-polyisoprene. The highly reactive thioaldehydes were generated from thiosulfinates in conventional rubber processing equipment. Monofunctional thiosulfinates were used to graft ester and amide functional groups to cis-1,4-polyisoprene. Oligomeric thiosulfinates were used to crosslink cis-1,4-polyisoprene under mild conditions. The networks formed using these new crosslinking agents are characterized. Good mechanical properties were obtained under optimized crosslinking conditions.

A case study on storage and capacity fading mechanism of poly(perylene diimides) cathode in aqueous zinc ion battery

Organic electroactive compounds can be applied as alternative cathodes in aqueous zinc ion batteries (AZIBs) with high stability and low toxicity. In the present study, the storage and capacity fading mechanism of a poly(perylene diimides) named OAP and its monomer, 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (PTCDA), is studied. As disclosed by the structural and electrochemical characterization, OAP exhibits larger capacity, better cycling stability and rate performance compared with the monomer PTCDA, which is due to the reduced solubility in the electrolyte, rougher surface and better tolerance to volume expansion. Electrochemical measurements and ex-situ characterization show that there are two storage ways in OAP-based AZIBs: (1) the redox reaction of the carbonyl groups. Compared with carbonyls in anhydrite groups, the redox reaction of carbonyls in imide groups exhibited better reversibility. (2) partially reversible intercalation and de-intercalation of zinc ion/proton between perylene structures. This work is meaningful for design novel and stable organic electrode materials for AZIBs.

Palladium-catalyzed dicarbonylation of terminal alkynes: A redox-neutral strategy for the synthesis of maleimides

A palladium-catalyzed redox-neutral dicarbonylation of terminal alkynes has been reported, in which hydroxylamine acts as both a nucleophile and a potential oxidant. Maleimides were synthesized in moderate yields under relatively mild conditions while avoiding the addition of equivalent oxidants. This reaction process involves two key steps: the addition of Pd-H to the terminal alkyne, and the hydroxylamine ester intermediate play the role of an internal oxidant via nucleophilic attack by hydroxylamine. This reaction has a wide range of functional group compatibility, and this internal oxidation reaction process also provided a new idea for other oxidative carbonylation reactions.

Mechanistic insights and computational design of Cu/M bimetallic synergistic catalysts for Suzuki-Miyaura coupling of arylboronic esters with alkyl halides

Carbonylative Suzuki-Miyura coupling reaction is one of the most efficient methods to synthetize ketones. In this work, the reaction mechanism of arylboronic esters with alkyl halides catalyzed by Cu/Mn synergistic catalysts has been studied by DFT calculation. The calculated results show that the whole reaction contains two cycles, one is the Cu-catalyzed transformation of Ar-Bneop to RO-Bneop, and the other is Mn-catalyzed Heck–Breslow cycle for alkyl halide carbonylation. At the last step, the final product aryl ketone is produced through the C-C cross-coupling between the two intermediates, which form from the above separate two cycles. For the title reaction, the [Mn(CO)5]− catalyzed the Heck–Breslow cycle belongs to SN2 mechanism, and Mn2(CO)10 catalyzed cycle is SET mechanism. In addition to [Mn(CO)5]−, the metal carbonyl anions with moderate even low nucleophilicity are suitable to co-catalyze the carbonylative Suzuki-Miyaura coupling with the Cu-carbene catalyst. Our calculation results are consistent with and provide explanations the experimental observations, as well as shed lights on further advancement of new bimetallic catalysts.

Transition‐Metal Catalyzed Coupling Reactions for the Synthesis of (Het)aryl Ketones: An Approach from their Synthesis to Biological Perspectives

AbstractSynthetic protocols capable of incorporating acyl based functional moieties have been proved fruitful to develop variety of carbonyl containing organic molecules. Substituted‐aromatic ketones are important motifs in different natural products and biologically active pharmaceuticals. Substituted aromatic ketones based compounds have been proved effective as antioxidant, antiallergic, antimicrobial, antimitotic, anticholinergic, antiinflammatory, anticonvulsant, antipsychotic age, anticancer, antimicrobial, antimalarial, and antiviral agents, Transition metals are necessary part of modern catalytic systems for carbonylative transformations. Carbonylative coupling reaction involves direct introduction of carbonyl fragment for synthesis of biaryls, aryl/alkyl ketones through transition metals based catalytic systems. In this review, we have reported the synthesis of biaryls, aryl/alkyl ketones by using different feed stocks in presence of various transition metal catalysts.

Sequential Strategies to Trigger Mild Dearomative Diels–Alder Cyclizations

Dihydronaphthalenes are present in several functional molecules, but their assembly is challenging. However, a sequential strategy can induce the key annullation of an alkyne with a vinylarene under mild conditions. Products form in good yields, with ample functional tolerance via domino nucleophilic substitution and dearomative Diels-Alder and ene reactions. DFT modeling data show that alkali cations are crucial to ensure a smooth dearomative cyclization on the in situ generated intermediates.

Palladium-Catalyzed Carbonylation for General Synthesis of Aurones Using CO2.

The carbonylation of alkynes using CO2 to generate aurones is to date unknown. In this study, a palladium-catalyzed carbonylation of terminal aromatic alkynes and the waste hydrosilane, poly(methylhydrosiloxane) (PMHS), is carried out with 2-iodophenol using CO2 to produce aurones. A variety of terminal alkynes and substituted 2-iodophenols are transformed into aurones in good yields. Preliminary mechanistic studies indicate that silyl formate, generated from CO2 and PMHS, plays a crucial role in the carbonylation reaction.

Palladium-Catalyzed Carbonylative Synthesis of Diaryl Ketones from Arenes and Arylboronic Acids through C(sp2)-H Thianthrenation.

The development of mild methodology for converting inert C-H bonds to value-added molecules has been an attractive research topic during the last few decades as it offers efficient preparation. Meanwhile, diaryl ketones hold potent applications in antitumor drugs, the agrochemical industry, and synthetic chemistry. Herein, we report versatile palladium-catalyzed carbonylative cross-coupling reactions of aryl thianthrenium salts with arylboronic acids. Arenes were transformed site selectively via C(sp2)-H thianthrenation, and various desired diaryl ketones were produced in good to excellent yields.

Scalable Palladium-Catalyzed C(sp3)–H Carbonylation of Alkylamines in Batch and Continuous Flow

Development of scalable processes for C(sp3)–H oxidative carbonylation of alkylamines is reported to provide convenient access to the β-lactam scaffol d. A study of the kinetics of the process revealed that the reaction is CO-limited even at elevated pressures and that there is an optimal CO concentration for the most effective outcome─this understanding led to an increase in the turnover number from 7 to 420 in the optimized process. Two scalable processes were then developed: a batch process, characterized by a very low catalyst loading, and a continuous process for an oxidative C–H carbonylation reaction that uses a copper-tube-flow reactor as a heterogeneous source of Cu2+ oxidant. The continuous process was tested on oxidative carbonylation of several alkylamines, yielding very good results with virtually no optimization required. This study thereby builds upon the utility of flow chemistry applications to oxidative carbonylations and scalable metal-catalyzed processes more generally.

Metal-Free Intermolecular Allylic C–H Amination of Alkenes Using Primary Carbamates

The allylic C–H amination of alkenes is a powerful method for the regioselective formation of new C–N bonds. Though many methods for introducing a wide range of nitrogen groups intermolecularly have been developed, few of these utilize carbamates, which are an important class of bioactive compounds and are commonly used as protecting groups for free amines. Here, we report a convenient metal-free protocol for intermolecular allylic C–H amination using unactivated primary carbamates as the nitrogen source. A sterically hindered NHC-selenium catalyst was found to be critical to obtaining high yields. A wide range of trisubstituted and 1,1-disubstituted alkenes were regioselectively aminated, including terpenoid natural products. A range of common carbamate-protecting groups such as Cbz, Teoc, and Alloc could be successfully incorporated into alkene substrates. Additionally, trifluoroacetamide was shown to be a viable nitrogen source. The observed regio- and stereoselectivities can be explained by a sequential ene reaction/[2,3]-sigmatropic rearrangement mechanism in which cis C–H bonds are preferentially activated, but subsequent rearrangement results in selective formation of trans alkene products.

Nickel-Catalyzed Carbonylative Coupling of Alkylzinc Reagents and α-Bromo-α,α-difluoroacetamides

AbstractWe report a nickel-catalyzed carbonylative cross-coupling of alkyl zinc reagents with α,α-difluorobromoacetamides to obtain α,α,-difluoro-β-ketoamides in moderate to good yields. The reaction is catalyzed by a bench-stable nickel(II) pincer complex, in contrast to other reports involving palladium catalysts. The carbonylative reaction is performed in a two-chamber system (COware) in which carbon monoxide (CO) is generated ex situ from the solid precursor SilaCOgen, and then consumed in the adjacent chamber. The reaction operates at low temperatures using near-stoichiometric amounts of CO. Isotopically labeled products can be effortlessly accessed, as demonstrated by using 13C-labeled SilaCOgen.