Primary Benzylic Alcohols Research Articles

Structure‐Guided Evolution of Aryl Alcohol Oxidase from Pleurotus eryngii for the Selective Oxidation of Secondary Benzyl Alcohols

AbstractAryl alcohol oxidase (AAO) is a fungal flavoenzyme capable of oxidizing aromatic primary alcohols into their correspondent aldehydes through a stereoselective hydride abstraction. Unfortunately, this enzyme does not act on secondary benzyl alcohols in racemic mixtures due to the strict control of substrate diffusion and positioning at the active site restricted to primary benzyl alcohols. Here we describe the engineering of AAO from Pleurotus eryngii to oxidize chiral benzyl alcohols with high enantioselectivity. The secondary benzyl alcohol oxidase was remodeled at the active site through four cycles of structure‐guided evolution, including a final step of in vivo site‐directed recombination to address the positive epistatic interactions between mutations. The final variant, with five substitutions and a renovated active site, was characterized at biochemical and computational level. The mutational sculpting helped position the bulkier (S)‐1‐(p‐methoxyphenyl)‐ethanol, improving the mutant's catalytic efficiency by three orders of magnitude relative to the native enzyme while showing a high enantioselectivity (ee >99%). As a promising candidate for racemic resolution, this evolved secondary benzyl alcohol oxidase maintained its natural stereoselective mechanism while displaying activity on several secondary benzyl alcohols.magnified image

Copper(I)- and Mesoionic-Hydroxyamide-Catalyzed Chemoselective Aerobic Oxidation of Primary Benzylic Alcohols

A new aerobic oxidation system consisting of Cu(I)I, 2,2'-bipyridine, N-methyl imidazole, and a mesoionic hydroxyamide was developed, with which selective oxidation of a broad range of benzylic alcohols was achieved.

Two-component boronic acid catalysis for increased reactivity in challenging Friedel-Crafts alkylations with deactivated benzylic alcohols.

A general and efficient boronic acid catalyzed Friedel-Crafts alkylation of arenes with benzylic alcohols was previously developed for the construction of unsymmetrical diarylmethane products (X. Mo, J. Yakiwchuk, J. Dansereau, J. A. McCubbin and D. G. Hall, J. Am. Chem. Soc., 2015, 137, 9694). Highly electron-deficient benzylic alcohols, however, were ineffective coupling partners due to the increased difficulty of C-O bond ionization. Herein, we report the use of perfluoropinacol as an effective co-catalyst to improve the reactivity of a boronic acid catalyst in the Friedel-Crafts benzylations of electronically deactivated primary and secondary benzylic alcohols. According to spectroscopic studies, it is believed that perfluoropinacol condenses with the arylboronic acid catalyst to form a highly electrophilic and Lewis acidic boronic ester. This in situ formed species enables a more facile ionization of the benzylic alcohols likely through a mode of activation promoted by a Lewis acid assisted hydronium Brønsted acid generated from the interactions of the transient boronic ester with hexafluoroisopropanol solvent and water.

Aerobic {Mo72V30} nanocluster‐catalysed heterogeneous one‐pot tandem synthesis of benzimidazoles

A novel heterogeneous one‐pot protocol is developed for tandem aerobic synthesis of benzimidazoles through dehydrogenative coupling of primary benzylic alcohols and aromatic diamines co‐catalysed by Keplerate‐type {Mo72V30} polyoxometalate and N‐hydroxyphthalimide (NHPI). The catalytic system also works well for the synthesis of benzimidazoles using benzaldehydes, as commonly used starting materials, in the absence of NHPI. The high activity of the solid nanocluster provides standard conditions avoiding current limitations of oxidation methods including high catalyst loadings. The spectral results and leaching experiments revealed that the nanocapsule preserved its structural integrity after being reused in consecutive runs.

Walnut Shell-Templated Ceria Nanoparticles: Green Synthesis, Characterization and Catalytic Application

Ceria (CeO2) nanoparticles (NPs) have been produced from cerium nitrate and walnut shell as a worthless agricultural waste by a thermal decomposition method followed by open air calcination. These NPs further were characterized using powder X-ray diffraction, transmission electron microscopy (TEM), scanning electron microscopy, energy dispersive X-ray spectroscope and Fourier transform infrared spectroscopy. Moreover, particle sizes can be tuned by changing cerium source/biomass ratio. To test the catalytic activity of cerium NPs as a heterogeneous catalyst, we selected three-component synthesis of 3,4-dihydroquinoxalin-2-amine. Also, the efficiency of CeO2 NPs as a support for palladium NPs and subsequent use in aerobic oxidation of alcohols has been investigated. TEM image of a recovered catalyst indicates the formation of 12 nm sized palladium NPs within the cerium oxide NPs. The catalyst is quite effective for the oxidation of primary and secondary benzylic alcohols into their corresponding aldehydes and ketones under atmospheric pressure of air. Oxidation of secondary aliphatic alcohols is performed in oxygen atmosphere.

Selective Single-Step Oxidation of Amine to Cross-Azo Compounds with an Unhampered Primary Benzyl Alcohol Functionality.

This is the first report of a single-step synthesis of primary benzyl alcohol containing different cross-azo compounds (14 examples) by Cu(II) in the presence of a newly synthesized amino-ether heteroditopic macrobicycle cage. Interestingly, even with extreme conditions, the benzyl alcohol remains unoxidized by the Cu(II) catalyst due to the protective etherial pocket of the cage.

Aerobic alcohol oxidation catalyzed by CuO-rectorite/TEMPO in water

An environmentally benign CuO-rectorite was prepared by calcining the co-precipitation product of Cu2+ with an acid-activated rectorite at pH 6. It could be well dispersed in water and used as a co-catalyst with TEMPO to selectively aerobically oxidize alcohols to aldehydes. The conversion of most primary benzylic alcohols was very high under optimized conditions. Interestingly, the oxidation protocol also allowed highly selective transformation of benzylic alcohols containing a phenolic hydroxyl group into the corresponding aldehydes. Additionally, very little copper was leached from the catalyst during the catalytic reaction. CuO-rectorite could be reused by centrifugation and washed with acetonitrile and water. At the same time, its catalytic activity remained high.

Chemoselective and Metal-Free Synthesis of Aryl Esters from the Corresponding Benzylic Alcohols in Aqueous Medium Using TBHP/TBAI as an Efficient Catalytic System

A novel and transition-metal-free strategy has been developed for the synthesis of aryl esters starting from corresponding benzylic primary alcohols as the exclusive substrates using tert-butyl hydroperoxide (TBHP) as a terminal oxidant in the presence of catalytic amount of tetrabutylammonium iodide (TBAI) and imidazole, where the aliphatic alcohols remained unaffected. These reactions are highly chemoselective and associated with high yield and wide applicability accommodating a wide range of substituents. Excellent chemoselectivity has also been demonstrated through intramolecular competition experiments. This protocol can be considered as an important analogue of Tishchenko reaction using benzylic alcohols as the substrates instead of benzaldehydes.

Selective, Efficient and Gram‐Scale Oxidation of Alcohols Using Household Bleach in the Presence of Fe3O4@Boehmite‐NH2‐CoII Nanoparticles

AbstractA new magnetic nanostructured core–shell‐like Fe3O4@Boehmite‐NH2‐CoII NPs as an environmentally friendly heterogeneous catalyst reported earlier by our group, has been found to be very effective for the oxidation of alcohols in aqueous media using household bleach at room temperature. The method has been applied for the oxidation of a range of primary and secondary benzylic, allylic and aliphatic alcohols with variable functionalities in excellent yields and selectivity. An aqueous medium, magnetic separation by an external magnetic field, low catalyst loading and catalyst reusability up to six runs without significant decrease in catalytic activity made the present procedure sustainable, economically viable and better than the most previously reported protocols.

Homogeneous Palladium-Catalyzed Transfer Hydrogenolysis of Benzylic Alcohols Using Formic Acid as Reductant.

We report the first homogeneous palladium-based transfer hydrogenolysis of benzylic alcohols using an in situ formed palladium-phosphine complex and formic acid as reducing agent. The reaction requires a catalyst loading as low as only 1 mol % of palladium and just a slight excess of reductant to obtain the deoxygenated alkylarenes in good to excellent yields. Besides demonstrating the broad applicability for primary, secondary and tertiary benzylic alcohols, a reaction intermediate could be identified. Additionally, it could be shown that partial oxidation of the applied phosphine ligand was beneficial for the course of the reaction, presumably by stabilizing the active catalyst. Reaction profiles and catalyst poisoning experiments were used to characterize the catalyst, the results of which indicate a homogeneous metal complex as the active species.

Controlled Aerobic Oxidation of Primary Benzylic Alcohols to Aldehydes Catalyzed by Polymer-Supported Triazine-Based Dendrimer–Copper Composites

A controlled aerobic oxidation of primary benzylic alcohols to the corresponding benzaldehydes by using polystyrene–poly­(ethylene glycol) (PS–PEG) resin-supported triazine-based polyethyleneamine dendrimer–copper complexes [PS–PEG-TD2–Cu(II)] was developed. In particular, PS–PEG-TD2–Cu(OAc)2 efficiently catalyzed the aerobic oxidation of benzylic alcohols in the presence of a catalytic amount of TEMPO under atmospheric conditions to give the corresponding aldehydes in up to quantitative yield. The catalyst was readily recovered by simple filtration and reused four times without significant loss of its catalytic activity.

Metal-Free Oxidative C(sp3)–N Coupling by HBr and DMSO: A Novel Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones

A metal-free oxidative C(sp3)–N coupling process has been developed for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones. The reaction between primary amines, isatoic anhydride, and benzylic alcohols in the presence of HBr in DMSO at 80 °C affords 2,3-dihydroquinazolin-4(1H)-ones in excellent yields. Under these reaction conditions, benzylic alcohols react with in situ generated bromodimethylsulfonium bromide to form alkoxysulfonium intermediates. These intermediates undergo an oxidative cyclization reaction with primary amines and isatoic anhydride to produce the title products.

Redox Noninnocent Azo-Aromatic Pincers and Their Iron Complexes. Isolation, Characterization, and Catalytic Alcohol Oxidation.

The new redox-noninnocent azoaromatic pincers 2-(arylazo)-1,10-phenanthroline (L1) and 2,9-bis(phenyldiazo)-1,10-phenanthroline (L2) are reported. The ligand L1 is a tridentate pincer having NNN donor atoms, whereas L2 is tetradentate having two azo-N donors and two N-donor atoms from the 1,10-phenanthroline moiety. Reaction of FeCl2 with L1 or L2 produced the pentacoordinated mixed-ligand Fe(II) complexes FeL1Cl2 (1) and FeL2Cl2 (2), respectively. Homoleptic octahedral Fe(II) complexes, mer-[Fe(L1)2](ClO4)2 [3](ClO4)2 and mer-[Fe(L2)2](ClO4)2 [4](ClO4)2, have been synthesized from the reaction of hydrated Fe(ClO4)2 and L1 or L2. The ligand L2, although having four donor sites available for coordination, binds the iron center in a tridentate fashion with one uncoordinated pendant azo function. Molecular and electronic structures of the isolated complexes have been scrutinized thoroughly by various spectroscopic techniques, single-crystal X-ray crystallography, and density functional theory. Beyond mere characterization, complexes 1 and 2 were successfully used as catalysts for the aerobic oxidation of primary and secondary benzylic alcohols. A wide variety of substituted benzyl alcohols were found to be converted to the corresponding carbonyl compounds in high yields, catalyzed by complex 1. Several control reactions were carried out to understand the mechanism of this alcohol oxidation reactions.

Chemoselective Continuous-Flow Hydrogenation of Aldehydes Catalyzed by Platinum Nanoparticles Dispersed in an Amphiphilic Resin

A chemoselective continuous-flow hydrogenation of aldehydes catalyzed by a dispersion of platinum nanoparticles in an amphiphilic polymer (ARP-Pt) has been developed. Aromatic and aliphatic aldehydes bearing various reducible functional groups, such as keto, ester, or amide groups, readily underwent flow hydrogenation in aqueous solutions within 22 s in a continuous-flow system containing ARP-Pt to give the corresponding primary benzylic or aliphatic alcohols in ≤99% yield with excellent chemoselectivity. Moreover, the long-term continuous-flow hydrogenation of benzaldehyde for 8 days was realized, and the total turnover number of the catalyst reached 997. The flow hydrogenation system provides an efficient and practical method for the chemoselective hydrogenation of aldehydes bearing reducible functional groups.

Aerobic oxidation of benzyl alcohols through biosynthesized palladium nanoparticles mediated by Oak fruit bark extract as an efficient heterogeneous nanocatalyst

In this study, green synthesis of Pd nanoparticles (NPs) is outlined through application of Oak fruit bark extract as a reducing, capping and stabilizing agent. The characteristics and properties of the biosynthesized Pd NPs were revealed by FESEM, EDX, XRD, TEM, UV–Vis, and FT-IR spectroscopies. So that, UV–Vis spectroscopy of the Pd colloidal solution confirmed reduction of Pd ions, and XRD and TEM analysis identified fcc unit cell structure forming 5–7nm spherical Pd NPs. Furthermore, catalytic activity of the prepared catalyst was investigated through aerobic oxidation of alcohols, as model reactions. Catalytic evaluations demonstrated achievement of good yields from primary and secondary benzyl alcohols. In general, the devised synthesis method is advantageous from several perspectives. For example, the synthesized catalysts give high product yields and are efficient, they eliminate the need for surfactant, chemical reductants, ligand and organic solvents, the approach is economically inexpensive, it results in cleaner reaction profiles, application of the simply prepared heterogeneous catalyst is convenient, and the catalyst is recoverable and reusable for at least six times without any significant loss of its catalytic activity.

Bimetallic cis-dioxomolybdenum(VI) complex containing hydrazone ligand: Syntheses, crystal structure and catalytic studies

Bimetallic molybdenum(VI) complex [(MoO2)2(slsch)(H2O)2] containing dihydrazone ligand was synthesized by reaction of ligand with MoO2(acac)2 in 1:2M ratio in methanol. The bimetallic complex obtained was characterized by various spectroscopic studies. The structure of complex was assigned using Single Crystal X-ray Crystallography and DFT method. We have also explored the catalytic behavior of complex for oxidation of primary benzylic, aliphatic, allylic, and propargylic alcohols.

Practical Aerobic Oxidation of Alcohols: A Ligand‐Enhanced 2,2,6,6‐Tetramethylpiperidine‐1‐oxy/Manganese Nitrate Catalyst System

AbstractA highly efficient, ligand‐enhanced 2,2,6,6‐tetramethylpiperidine‐1‐oxy (TEMPO)/Mn(NO3)2 catalyst system for the aerobic oxidation of alcohols is described. From the series of coordinating ligands studied herein, 2‐picolinic acid (PyCOOH) improves the catalytic activity of TEMPO/Mn(NO3)2 remarkably. Under ambient air at room temperature in acetic acid, the ligand‐enhanced catalyst converts aliphatic and benzylic primary alcohols that bear various functional groups into their respective aldehydes with near quantitative conversions. The applicability of the catalyst for convenient preparative synthesis was demonstrated by conducting oxidations on a gram scale. A change of TEMPO to the sterically less demanding 9‐azabicyclo[3.3.1]nonane N‐oxyl results in a Mn catalyst that is also able to oxidize secondary alcohols to ketones. Mechanistic studies showed that alcohols are oxidized by the oxoammonium cation derived from the nitroxyl radical. The active oxidant is regenerated by Mn(NO3)2, and this process is greatly promoted by the coordination of PyCOOH to Mn.

An Efficient and Environmentally Benign Bentonite–Gold Nanohybrid‐Catalyzed Oxidative Cross‐Coupling of Ketones with Benzylic Primary Alcohols

AbstractAn efficient, green and sustainable method for the oxidative C−C coupling of ketones and primary alcohols was developed using an environmentally benign bentonite–gold nanohybrid catalyst. This heterogeneous catalyst affords diverse α,β‐unsaturated ketones in excellent yields under ambient reaction conditions in the presence of Cs2CO3 as weak base. The catalyst is selective, recyclable and only water is produced as the side product. This catalytic system is readily applicable for the gram‐scale synthesis of α,β‐unsaturated ketones.

Iron-Catalyzed Direct C3-Benzylation of Indoles with Benzyl Alcohols through Borrowing Hydrogen.

We present the coupling of primary and secondary benzyl alcohols with indoles to form 3-benzylated indoles and H2O that is catalyzed, for the first time, by a complex of earth-abundant iron. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, sustainability, high functional-group tolerance, and amenability to gram-scale synthesis. On the basis of the preliminary experimental observations, we propose that the reaction proceeds through a borrowing hydrogen process.

Nitrogen dioxide-catalyzed aerobic oxidation of benzyl alcohols under cocatalyst and acid-free conditions

Nitrogen dioxide is usually considered as a mediator between dioxygen and the catalysts for the aerobic oxidation of alcohols. Here, we report that nitrogen dioxide has an ability to catalyze this reaction, which not only avoids the use of the cocatalysts or the acids in traditional approaches, but also reveals a method for the present transformation with a single component catalyst. A series of primary and secondary benzyl alcohols underwent this transformation to give the targeted products in low to high yields.