Synthesis and antifungal property of N-(aryl) and quaternary N-(aryl) chitosan derivatives against Botrytis cinerea

A series of N-(aryl) and their quaternary N-(aryl) chitosan derivatives were synthesized and evaluated for their antifungal activity against crop-threatening fungus Botrytis cinerea. Schiff bases were firstly synthesized by the reaction of chitosan with cinnamaldehyde, cuminaldehyde and 4-dimethylaminobenzaldehyde followed by reduction with sodium borohydride to form N-(aryl) chitosans. Quaternary N-(aryl) chitosans were then obtained by reaction of N-(aryl) chitosan compounds with ethyl iodide. The chemical structures were characterized by ¹H-NMR, FT-IR and UV spectroscopic techniques. The antifungal activity was evaluated in vitro against B. cinerea by mycelial growth inhibition method and in vivo by application of compounds to tomato plants prior to inoculation with fungal spores. In an in vitro experiment, all quaternized chitosans were more active than N-(aryl) chitosan derivatives and N,N,N-(diethylcinnamyl) chitosan (QC1) was the most potent (EC₅₀ = 1,147 mg/L) against mecelia however, N,N,N-(diethyl-p-dimethylaminobenzyl) chitosan (QC3) was the most potent (EC₅₀ = 334 mg/L) against spores. In an in vivo study, no disease incidence (0.0 %) was observed with QC1 and QC3 at 1,000 mg/L. Spray liquid chitosan enhanced total phenolics and guaiacol peroxidase in inoculated leaves.     

Iron/copper co-catalyzed highly selective arylation of sulfinamides with aryl iodides

In the present study, an inexpensive but efficient Iron(III) and Copper(II) co-catalyst without ligands catalyzed arylation of sulfinamides with aryl iodide was primarily reported. In brief, in the presence of Fe(NO₃)₃·9H₂O, CuO and K₃PO₄, the highly selective C–N cross coupling of several sulfinamides and aryl iodides was achieved in high chemical yield, while the aryl chlorides and bromides could not yield coupling products. It is noteworthy that through the arylation of chiral tert-butanesulfinamide with aryl iodides, N-aryl tert-butanesulfinamides are provided without racemization, even in gram-scale. The possible mechanism was that This oxidative addition process between copper catalyst and aryl-iodides might be significantly accelerated by active Fe(III) species. Moreover, using this synthetic method, a facile and efficient access was developed for the derivatives of N-phenyl sulfinamides, which might help to develop new drug molecules and material chemicals.     

Tetraphosphine/palladium catalysed Suzuki cross-coupling reactions of aryl halides with alkylboronic acids

Through the use of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides and chlorides undergoes Suzuki cross-coupling with alkylboronic acids in good yields. Several alkyl substituents such as ethyl, n-butyl, n-octyl, isobutyl or 2,2-dimethylpropyl on the alkylboronic acids have been successfully used. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides.     

Heck reactions of 2-substituted enol ethers with aryl bromides catalysed by a tetraphosphine/palladium complex

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of β-substituted enol ethers with aryl bromides. Employing β-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate, the regioselective α-arylation of these enol ethers was observed in all cases, and mixtures of Z and E isomers were generally obtained, which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and electronic factors, and better stereoselectivities in favour of Z isomers were observed with electron-rich or sterically congested aryl bromides. Better yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-poor aryl bromides. This observation suggests that with these β-substituted enol ethers the rate-limiting step of the catalytic cycle is not the oxidative addition of the aryl bromide to the palladium complex.     

Palladium-catalysed direct arylations of NH-free pyrrole and N-tosylpyrrole with aryl bromides

The palladium-catalysed direct coupling of aryl halides with pyrroles provides a greener access to arylated pyrroles than more classical couplings such as Suzuki, Stille or Negishi reactions. However, so far, NH-free pyrrole and N-tosylpyrrole gave disappointing results for such couplings either in terms of regioselectivity of the arylation, catalyst loading or substrate scope. The reactivity of both NH-free pyrrole and N-tosylpyrrole was studied, and the tosylated pyrrole led to higher yields of coupling products due to better conversions of the aryl bromides. A range of aryl bromides undergo regioselective coupling at C2 of N-tosylpyrrole in moderate to good yields using 1 mol % [Pd(Cl(C₃H₅)]₂ as the catalyst, KOAc as the base in DMAc.     

Copper-catalyzed cross-coupling of sulfonamides with aryl iodides and bromides facilitated by amino acid ligands

A highly general, convenient, and inexpensive catalyst system was developed for the N-arylation of sulfonamides with aryl iodides or bromides by using 5-20 mol % of CuI as catalyst, 20 mol % of N-methylglycine (for aryl iodides) or N,N-dimethylglycine (for aryl bromides) as ligand, and K₃PO₄ as base.     

Unusual redox play of Mo(V/IV) during oxidative aryl–aryl coupling

The oxidative treatment of a suitable 1,3-diarylpropene precursor by MoCl₅ causes a series of redox steps yielding a dimer of dibenzo[a,c]cycloheptene. After the oxidative aryl–aryl bond formation, a C,H activation occurs providing a tropylium intermediate. Upon aqueous workup the metal waste acts as reductive media generating the dimer in an almost quantitative manner. The oxidative generation of the tropylium species as well as the subsequent redox play by the metal waste is unique and unprecedented. The dimeric compound can be oxidatively cleaved and subsequently decarboxylated providing the key intermediate of a previous synthesis of metasequirin-B derivatives.     

Cleavable and tunable cysteine-specific arylation modification with aryl thioethers

Cysteine represents an attractive target for peptide/protein modification due to the intrinsic high nucleophilicity of the thiol group and low natural abundance. Herein, a cleavable and tunable covalent modification approach for cysteine containing peptides/proteins with our newly designed aryl thioethers via a S_NAr approach was developed. Highly efficient and selective bioconjugation reactions can be carried out under mild and biocompatible conditions. A series of aryl groups bearing different bioconjugation handles, affinity or fluorescent tags are well tolerated. By adjusting the skeleton and steric hindrance of aryl thioethers slightly, the modified products showed a tunable profile for the regeneration of the native peptides.

A cleavable and tunable covalent modification approach for cysteine by aryl thioethers via a S_NAr approach was developed. The highly efficient and selective bioconjugation reactions can proceed under the mild and biocompatible conditions.     

Palladium catalyzed-dehalogenation of aryl chlorides and bromides using phosphite ligands

The catalytic system based on Pd-phosphite for the dehalogenation reactions of aryl chlorides and bromides is described. The Pd-phosphite catalyst effectively promoted the dehalogenation of aryl halides to give dehalogenated products in moderate to excellent yields. The aryl chlorides required strong bases such as NaO^tBu for this transformation, whereas the aryl bromides were dehalogenated in the presence of weak bases such as Cs₂CO₃. This catalytic system exhibited tolerance to functional groups such as methoxy, amine, hydroxyl, ether, amide, benzyl and ketone groups. It also demonstrated chemoselectivity in that bromochlorobenzene was converted only to chlorobenzene.     

Sonogashira cross-coupling reactions of aryl chlorides with alkynes catalysed by a tetraphosphine-palladium catalyst

A range of aryl chlorides undergoes cross-couplings with alkynes in good yields in the presence of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst. A variety of aryl chlorides such as chloroacetophenone, chlorobenzonitrile, chloronitrobenzene, chloroanisole or chlorotoluene have been used successfully. The reaction also tolerates several alkynes such as phenylacetylene, dec-1-yne, ethynylcyclohexene or alk-1-ynols. Furthermore, this catalyst can be used at low loading with some substrates.     

An efficient catalyst system for diaryl ether synthesis from aryl chlorides

The combination of 2-phosphino-substituted N-arylpyrroles or related indoles (cataCXium^®P) and Pd(OAc)₂ allows for efficient cross-coupling reactions of aryl chlorides and phenols to give diaryl ethers. A variety of aryl and heteroaryl chlorides can be coupled with substituted phenols showing unprecedented catalyst turnover numbers.     

Highly efficient synthesis of aryl ketones by PEPPSI-palladium catalyzed acylative Suzuki coupling of amides with diarylborinic acids

An improved acylative cross-coupling of various N-methyl-N-tosyl amides with diarylborinic acids for synthesis of aryl ketones is developed. In most cases, aryl ketones could be obtained in excellent yields by using 1?mol% 2,6-diisopropylphenylimidazolylidene and 3-chloropyridine co-supported palladium chloride as catalyst in the presence of 3 equiv. K₂CO₃ as base in refluxing THF. The readily prepared and cost-effective substrates, N-methyl-N-tosylamides and diarylborinic acids, and the commercially available catalyst system promise a practical and efficient access to aryl ketones.     

Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.     

Oxidative addition of aryl chlorides to palladium N-heterocyclic carbene complexes and their role in catalytic arylamination

Density functional theory has been used to investigate various solvated species that may be formed from palladium bis N-heterocyclic carbene complexes, [Pd(cyclo-C{NRCH}₂)₂], (PdL₂) in benzene solution. Formation of an η²-arene complex is shown to stabilise a monocarbene species, PdL(η²-C₆H₅X), where the arene is either the solvent or a reacting aryl halide. Oxidative addition of an aryl chloride has been modelled, and the most likely transition state has been established as a PdL(arylchloride) species, with just one carbene ligand coordinated to the palladium. The catalytic cycle for aryl amination has been investigated and the oxidative addition of the aryl halide shown to be the rate determining step. Reductive elimination of the aryl amine has a lower activation energy. Oxidative addition of alkyl halides has been shown to be less favourable because of the absence of an unsaturated group, such as the aryl ring, to bond to the palladium.     

Direct synthesis of 3-arylpropionic acids by tetraphosphine/palladium catalysed Heck reactions of aryl halides with acrolein ethylene acetal

Through the use of [PdCl(C₃H₅)]₂/Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides.     

Heck reactions of aryl bromides with alk-1-en-3-ol derivatives catalysed by a tetraphosphine/palladium complex

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of alk-1-en-3-ol with a variety of aryl bromides. In the presence of hex-1-en-3-ol or oct-1-en-3-ol, the β-arylated carbonyl compounds were selectively obtained. Linalool and 2-methylbut-3-en-2-ol led to the corresponding 1-arylalk-1-en-3-ol derivatives. Turnover numbers up to 69,000 can be obtained for this reaction. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as bromoacetophenone and deactivated aryl bromides such as bromoanisole.     

Efficient copper-catalyzed coupling of aryl iodides and thiobenzoic acid

A highly efficient copper-catalyzed coupling reaction of aryl iodides and thiobenzoic acid, using 10 mol % of copper iodide, 20 mol % of 1,10-phenanthroline, and ⁱPr₂NEt in toluene, was developed. This methodology is applicable to a variety of aryl iodides.     

Gold(I)-catalyzed direct C-H arylation of pyrazine and pyridine with aryl bromides

An efficient procedure for the direct C-H arylation of electron-poor aromatics such as pyrazine and pyridine with aryl bomides is described. In the presence of catalytic amount of Cy₃PAuCl and with the use of t-BuOK as base, pyrazine undergoes the direct C-H arylation with aryl bromides at 100 °C, and the yields of the arylated products depend on the nature of aryl bromides. In the cases of electron-rich aryl bromides used, the arylated pyrazines can be obtained in good to high yields. For electron-poor aryl bromides, the addition of AgBF₄ is the crucial point to accelerate the coupling reaction to give the arylated products in moderate yields. Pyridine also reacts with electron-rich aryl bromides catalyzed by Cy₃PAuCl to give a mixture of arylated regioisomers in moderate yield. However, in order to realize the direct C-H arylation of pyridine with electron-poor aryl bromides, the addition of silver salt as additive and a milder reaction temperature (60 °C) are required.     

A simple, base-free preparation of S-aryl thioacetates as surrogates for aryl thiols

A mild method for the preparation of S-aryl thioacetates by hetero cross-coupling reactions of aryl bromides or aryl triflates with potassium thioacetate is described. The reaction proceeded smoothly in toluene at 110 °C, mediated by catalytic Pd₂(dba)₃ in combination with CyPF-tBu as the ligand. Neither the presence of a base nor microwave conditions were required. The formed S-aryl thioacetate proved to be stable under flash chromatographic conditions and could be rapidly converted into the corresponding thiol under mildly basic conditions.     

Investigation of the scope and mechanism of copper catalyzed regioselective methylthiolation of aryl halides

Methylthiolation of structurally diverse aryl halides was accomplished under fluoride free conditions using catalytic amounts of CuI, and DMSO as the methylthiolation source. Optimization studies unveiled several varieties of promoters among which Zn(OAc)₂ was found ideal. The analogous reaction with DMSO-d₆ afforded corresponding deuterated aryl methyl thioether with 99% purity. Mechanistic studies revealed CuSMe as the active methylthiolation agent.