Acetoxylation Reaction Research Articles

Preparation of Fluorous Aza-crown Ether with Two Bisfluorous Chain Type Propionyl Groups: An Investigation of its Partition Ratios in Fluorous Biphasic Systems and Recyclability During SN2-type Acetoxylation Reactions

Abstract: In this study, a new fluorous aza-crown ether derivative (1) conjugated with two Bfp (bisfluorous chain type propionyl) groups was prepared; then, the partition ratios of 1 in biphasic systems using FC 72 and several organic solvents were investigated. Next, the activities of 1 in an FC 72/acetonitrile biphasic system were assessed via the SN2-type acetoxylation reaction using 2- (bromomethyl)naphthalene and potassium acetate. Finally, the recyclability of 1 in a two-layer system based on its immobilization in an FC 72 solvent was examined during acetoxylation reactions.

Mono and di ortho-C-H acetoxylation of 2-aryloxyquinoline-3-carbaldehydes.

2-Aryloxyquinolines are well known for various biological activities. In this report, we have developed a novel protocol for introducing an acetoxy functional group on the aryl sp2 carbon of 2-aryloxyquinoline-3-carbaldehyde using a palladium catalyst for the first time. Interestingly, this C-H acetoxylation reaction is highly chemo- and site-selective. By modifying the reaction conditions, mono or di ortho-C-H acetoxylation products have been synthesized selectively with good yields and with good functional group tolerance.

Effect of Pyrolysis Conditions on the MOFs-Derived Zinc-Based Catalysts in Acetylene Acetoxylation

The preparation method and calcination temperature of metal-organic framework (MOFs)-derived materials are critical factors affecting catalytic performance. In this work, the preparation conditions of MOFS precursors were optimized, and zinc-based catalysts with different activities (MOF5-700, MOF5-750, and MOF5-800) were obtained by pyrolysis of MOFS precursors under nitrogen, which were then applied to an acetylene acetoxylation reaction system. According to the results, the conversion rate of acetic acid under catalysis was significantly different. (MOF5-700 (48%), MOF5-750 (62%), and MOF5-800 (22%)). Comparing the activity of the catalyst with the industrial catalyst Zn(OAc)2/AC (20%), MOF5-750 showed higher activity, and the acetic acid conversion rate remained around 60% after 50 h of stability testing. By characterization analysis, MOFs-derived materials were obtained after proper temperature pyrolysis. They have high mesoporous content, defects, and oxygen-containing functional groups and can maintain a good crystal structure, greatly reducing the loss of active components. This is the main reason for the good performance of the MOF5-750 catalyst in acetylene acetoxylation. Thus, the preparation conditions and favorable pyrolysis temperature of MOF derivative catalysts play a key role in the catalytic performance of acetylene acetoxylation.

Syntheses of Two New Fluorous Crown Ethers Carrying Sugar Molecules with a Multivalent Bfp Modification: Investigations of Their Partition Ratios in Fluorous Biphasic Systems and Recyclability During Acetoxylation Reaction

Syntheses of Two New Fluorous Crown Ethers Carrying Sugar Molecules with a Multivalent Bfp Modification: Investigations of Their Partition Ratios in Fluorous Biphasic Systems and Recyclability During Acetoxylation Reaction

Mechanistic Details of the Pd-catalyzed and MPAA Ligand-Enabled β-C(sp3)-H Acetoxylation of Free Carboxylic Acid.

Transition metal-catalyzed C-H bond oxidation of free carboxylic acid stands as an economic, selective, and efficient strategy to generate lactones, hydroxylated products, and acetoxylated products and attracts much of the chemists' attention. Herein, we performed a density functional theory study on the mechanism and selectivity in Pd-catalyzed and MPAA ligand-enabled C-H bond acetoxylation reaction. It was found that the ligand, base, and substrate are important in determining the reaction mechanism and the selectivity. The acetic anhydride additive is critical in leading the reaction to be acetoxylation, instead of the lactonization, through a facile σ-bond metathesis mechanism that leads to the Pd-OAc in-termediate. Our study sheds light on the further development of transition metal-catalyzed C-H bond oxidation reactions.

Palladium‐catalyzed CH acetoxylation of arenes using a pyrazolonaphthyridine ligand

AbstractHerein, Pd‐catalyzed CH acetoxylation reactions of arenes are developed using a pyrazolonaphthyridine ligand. In the presence of iodomesitylene diacetate as the oxidant, the electron‐deficient ligand facilitates the CH activation of the electron‐rich positions while preventing the formation of Pd black via bidentate binding. Although both acetic acid and hexafluoroisopropanol are employed for directing group‐assisted acetoxylation reactions, the latter proved to be more efficient for the nondirected reaction of arenes with the nitrogen ligand.

Direct Acetoxylation of Arenes.

Acetoxylation of arenes is an important reaction and an unmet need in chemistry. We report a metal-free, direct acetoxylation reaction using sodium nitrate under an anhydrous environment of trifluoroacetic acid, acetic acid, and acetic anhydride. Arenes (31 examples), with oxidation potentials (Eox, in V vs SCE) lower than benzene (2.48 V), were acetoxylated with good yields and regioselectivity. A stepwise, single electron-transfer mechanism is proposed.

C-N and C-O Bond Formation in Copper-Catalyzed/Mediated sp3 C-H Activation: Mechanistic Studies from Experimental and Computational Aspects.

Mechanistic studies on Cu-catalyzed/mediated sp3 C-H amidation and acetoxylation are investigated from experimental and computational aspects. The concerted metalation-deprotonation (CMD) mechanism rather than a radical-involved pathway is proved to occur in amidation and acetoxylation reactions, and this is the rare example of the CMD mechanism involved in the more challenging sp3 C-H activations. Theoretical calculations demonstrated that CMD is the rate-determining step either for methylic or benzylic positions in amidation and acetoxylation reactions, and intermolecular nucleophilic addition of acetate anions is more favorable than the ring opening of β-lactams and intramolecular acetoxylation. These mechanistic studies on the divergent and condition-dependent product formation are critical for developing Cu-promoted C-H functionalization via the CMD mechanism.

C-H Halogenation of Pyridyl Sulfides Avoiding the Sulfur Oxidation: A Direct Catalytic Access to Sulfanyl Polyhalides and Polyaromatics.

Palladium-catalyzed oxidative C–H halogenation and acetoxylation reactions of S-unprotected sulfides, selectively directed by pyridinyl groups, allows the formation of C–X bonds (X = I, Br, Cl, OAc) by using simple halosuccinimide or phenyliodine diacetate (PIDA) oxidants. The undesired formation of sulfoxides and/or sulfones, which are usually observed under oxidative conditions, is fully obviated. Under the solvent-dependent conditions that we proposed, sulfide C–H functionalization is achieved in less than 1 h without any direct electrophilic halogenation at the pyridine moiety. N-Directed ortho-C–H activation of aryl also facilitates dibromination reactions which are hardly accessible with sulfone and sulfoxide counterparts because of their higher structural rigidity. This general method gives a straightforward access to polyhalide sulfides, without an organosulfur reduction step or protection–deprotection sequence. Polyhalide sulfides are valuable synthons that give a practical entry to new constrained polyaromatic and biphenyl sulfides, including synthetically challenging unsymmetrical examples.

Liquid-Phase Synthesis of N-Functionalized Azanucleoside-Incorporated Oligonucleotides and Development of Anodic C(sp3)–H Acetoxylation Reaction for Direct Preparation of Azaribose

We report the synthesis of pyrene-conjugated azanucleoside-incorporated oligodeoxynucleotides (aza-ODNs). Combination of liquid-phase synthesis by alkyl-chain-soluble-support (ACSS) and electrochemical C–H activation realized efficient access to aza-ODNs without requiring an excess amount of reagent or solvent. The fluorescent properties of pyrene-conjugated aza-ODNs were also investigated. The resulting fluorescence spectrum indicated that the modification of the position of the nitrogen atom was suitable for the preparation of artificial functionalized oligonucleotides. A synthetic route to azaribose, as a precursor of aza-ODNs, was also reinvestigated to realize more efficient production. Electrochemical N-α-acetoxylation in 0.1 M lithium perchlorate/nitromethane/50 mM AcOH medium was found to be a suitable medium for this route. These results represent a new efficient synthetic route to aza-ODNs.

Enantioselective Total Synthesis of (+)-Arboridinine.

The enantioselective total synthesis of cage-shaped alkaloid (+)-arboridinine is reported. The synthesis takes advantage of the stereoselective double-Mannich reaction to rapidly construct the aza[3.3.1]bicyclic core along with two quaternary stereocenters of the alkaloid. Key steps for the present synthesis include an enantioselective Michael addition establishing the original chiral center at C10 and intramolecular dearomative alkylation forging the cage-shaped ring system found in arboridinine, as well as creating the requisite quaternary carbon center at C3. The bridgehead hydroxyl moiety at C11 was installed through a late-stage cobalt-catalyzed decarboxylative acetoxylation reaction. This strategy enables a 14-step asymmetric total synthesis of (+)-arboridinine from the readily available starting materials with most of the transformations performed on the decagram scale.

In situ XAS study of the local structure and oxidation state evolution of palladium in a reduced graphene oxide supported Pd(ii) carbene complex during an undirected C–H acetoxylation reaction

In situ XAS is used to reveal the evolution of palladium species during an undirected C–H acetoxylation reaction.

Mechanistic investigation into the C(sp3)-H acetoxylation of morpholinones.

The study of a selective palladium(ii)-catalyzed C(sp3)-H acetoxylation reaction on a class of cyclic alkyl amines is reported. Computational modelling and kinetic studies were used to provide support for a mechanism involving selective C-O bond formation from a γ-aminoalkyl-Pd(iv) intermediate. The C-O bond forming step was computed to occur by a dissociative ionization mechanism followed by an SN2 process involving external acetate attack at the C-Pd(iv) bond. This pathway was computed to be of lowest energy with no competing C-N products observed. Additionally, with a few modifications to reaction conditions, preliminary studies showed that this process could be rendered enantioselective in the presence of a non-racemic BINOL-phosphoric acid.

A PdII Carbene Complex with Anthracene Side‐Arms for π‐Stacking on Reduced Graphene Oxide (rGO): Activity towards Undirected C–H Oxygenation of Arenes

An N‐heterocyclic carbene palladium(II) complex containing two anthracene side arms was immobilized on the surface of reduced graphene oxide (rGO) by π‐stacking. The activity of the homogeneous analogue and the supported complex in undirected C–H acetoxylation reaction of arenes was studied. The results show that the catalytic efficiency in acetoxylation of benzene is improved in the immobilized materials compared to the homogeneous analogue. According to XPS analysis, the immobilized catalyst maintains the original oxidation state of PdII after the catalytic reaction.

A Novel High-Activity Zn-Co Catalyst for Acetylene Acetoxylation

In this paper, Zn(OAc)2/AC and Zn-Co/AC catalysts were prepared and applied in an acetylene acetoxylation reaction. Compared with monometallic Zn(OAc)2/AC catalyst, which is widely applied in industry, the Zn-Co catalysts exhibited excellent catalytic performance. Transmission electron microscopy results displayed that the addition of cobalt improved the dispersity of zinc acetate particles and inhibited catalyst sintering on the catalyst surface. X-ray photoelectron spectra suggested that the Co additive changed the electron density of zinc acetate probably because of the interaction between Zn and Co species. Temperature programmed desorption analysis demonstrated Co additive strengthened the adsorption of acetic acid and weakened the adsorption of acetylene.

Rhodium-Catalyzed sp2 C-H Acetoxylation of N-Aryl Azaindoles/N-Heteroaryl Indolines.

A silver- and copper-free rhodium-catalyzed C-H acetoxylation reaction of azaindoles has been achieved at near ambient temperature employing PIDA as a nonmetallic acetoxy source. The method is highly selective, efficient, and scalable and requires acetic anhydride as the sole additive. The scope of the reaction has been successfully tested with a wide array of medicinally important heterocyclic scaffolds with diverse functional group tolerance. A series of kinetic experiments was conducted to gain detailed insight into the reaction mechanism. The methodology developed could be successfully expanded for C7-acetoxylation of indoline derivatives using pyrimidine as a detachable directing group for the synthesis of 7-hydroxyindole.

Diversification of Quinazolinones by Pd-Catalyzed C(sp3)-Acetoxylation.

The quinazolinone ring has been exploited as a directing group for C(sp3)-H functionalization for the first time. The proximal C-γ(sp3)-H bonds have been oxidized by palladium-catalyzed acetoxylation reaction. Various functional groups on the quinazolinone scaffold were tolerated to provide novel quinazolinone derivatives. The use of base was found to be crucial for the monoselective acetoxylations.

PhI(OAc)2-promoted umpolung acetoxylation of enamides for the synthesis of α-acetoxy ketones

Umpolung is a fundamental concept in organic chemistry, which provides an alternative strategy for the synthesis of target compounds which were not easily accessible by conventional methods. Herein, a mild and efficient PhI(OAc)2-promoted umpolung acetoxylation reactions of enamides was developed for the synthesis of α-acetoxy ketones. The reaction tolerates a wide range of functional groups and affords α-acetoxy ketones in good to excellent yields. PhI(OAc)2 serves as a source of acetoxy in the reaction.

Redox Couple Involving NOx in Aerobic Pd-Catalyzed Oxidation of sp3-C-H Bonds: Direct Evidence for Pd-NO3-/NO2- Interactions Involved in Oxidation and Reductive Elimination.

NaNO3 is used in oxidative Pd-catalyzed processes as a complementary co-catalyst to common oxidants, e.g., CuII salts, in C-H bond activation and Wacker oxidation processes. NaNO3 and NaNO2 (with air or O2) assist the sp3-C-H bond acetoxylation of substrates bearing an N-directing group. It has been proposed previously that a redox couple is operative. The role played by NOx anions is examined in this investigation. Evidence for an NOx anion interaction at PdII is presented. Palladacyclic complexes containing NOx anions are competent catalysts for acetoxylation of 8-methylquinoline, with and without exogenous NaNO3. The oxidation of 8-methylquinoline to the corresponding carboxylic acid has also been noted at PdII. 18O-Labeling studies indicate that oxygen derived from nitrate appears in the acetoxylation product, the transfer of which can only occur by interaction of 18O at Pd with a coordinating-acetate ligand. Nitrated organic intermediates are formed under catalytic conditions, which are converted to acetoxylation products, a process that occurs with (50 °C) and without Pd (110 °C). A catalytically competent palladacyclic dimer intermediate has been identified. Head-space analysis measurements show that NO and NO2 gases are formed within minutes on heating catalytic mixtures to 110 °C from room temperature. Measurements by in situ infrared spectroscopy show that N2O is formed in sp3-C-H acetoxylation reactions at 80 °C. Studies confirm that cyclopalladated NO2 complexes are rapidly oxidized to the corresponding NO3 adducts on exposure to NO2(g). The investigation shows that NOx anions act as participating ligands at PdII in aerobic sp3-C-H bond acetoxylation processes and are involved in redox processes.

Catalytic Multisite-Selective Acetoxylation Reactions at sp2 vs sp3 C-H Bonds in Cyclic Olefins.

The first Pd-catalyzed multisite-selective acetoxylation reactions are disclosed at an unactivated alkene sp2 C-H bond versus secondary allylic sp3 C-H bond in cyclic olefins via the modulation of directing groups. The different directing groups overcome the key challenge in differentiating C-H bonds and provide a new controlling approach for site-specific C-H activation. A wide variety of substrates are readily acetoxylated under operationally simple conditions. Mechanistic studies suggest that different Pd (IV) intermediates were involved in the multisite-selective acetoxylation reactions.