Transition metal free oxidative esterification of alcohols with toluene

Using Bu₄NI as the catalyst and tert-butyl hydroperoxide as the oxidant, direct esterification of alcohols with toluene derivatives was achieved. Mechanistic investigations indicate that the alcohols are sequentially oxidized to aldehydes, carboxylic acids, and then to benzyl esters. Bu₄N⁺ functions as a phasetransfer reagent and iodide catalyzes the reaction.     

Cl3CCONH2/PPh3: A Versatile Reagent for Synthesis of Esters

Cl₃CCONH₂/PPh₃ was a versatile reagent to convert carboxylic acids into their corresponding acid chlorides. This intermediate was clearly confirmed by spectroscopic methods (IR, ¹H, ¹³C NMR). This one-pot reaction of in situ acid chloride generated with various alcohols successfully furnished the corresponding esters in moderate to excellent yields.     

An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator

A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propanephosphonic acid cyclic anhydride (T3P) and subsequent reduction using NaBH₄ yield the alcohol in excellent yields with good purity. Reduction of several alkyl/aryl carboxylic acids and N^α-protected amino acids/peptide acids as well as N^β-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields. All the products were fully characterized by ¹H NMR and mass spectral analyses. The procedure is mild, simple and the isolation of the products is easy.     

Reactivity of chlorinating agents/PPh3 for the chlorination of alcohols and carboxylic acids: a comparative study

The reactivity of chlorinating agents was examined with the aid of ¹H NMR using competitive reactions between selected chlorinating agents and CBr₄ towards alcohols and carboxylic acids. The reactivity was greatly dependent on the type of substituent on the chlorinating agents. COCCl₃ and CN substituted trichloromethyl groups enhanced the reactivity of the chlorinating agent with PPh₃ for the chlorination of alcohols and carboxylic acids.     

Highly Efficient System for Reduction of Carboxylic Acids and Their Derivatives to Alcohols by HfCl4/KBH4

HfCl₄/KBH₄ was found to be a facile, efficient, convenient, and chemoselective system for the reduction of carboxylic acids and their derivatives to the corresponding alcohols under mild conditions. HfCl₄/NaBH₄ was also utilized to reduce the same carboxylic acids and their derivatives, and it was found that the reducing ability of HfCl₄/NaBH₄ was similar to that of HfCl₄/KBH₄. The action of HfCl₄/KBH₄ on other types of substrates, such as benzyl chloride, peracid, epoxide, ketone, amide, imine, pyridine-N-oxide, and nitrile, was investigated, too. In addition, some competitive reductions of styrene oxide in the presence of carboxylic acid, carboxylic ester, nitrile, and amide were achieved.     

Perylen-3-ylmethyl: fluorescent photoremovable protecting group (FPRPG) for carboxylic acids and alcohols

Perylen-3-ylmethyl demonstrated as a new fluorescent photoremovable protecting group (FPRPG) for carboxylic acids and alcohols. Carboxylic acids including amino acids were protected as their corresponding esters by coupling with FPRPG, perylen-3-ylmethyl. Photophysical studies of caged esters showed that they all exhibited strong fluorescence properties and their fluorescence quantum yields were in the range of 0.85–0.95. Irradiation of the caged esters using visible light (≥410 nm) in aqueous acetonitrile released the corresponding carboxylic acids in high chemical (94–97%) and quantum (0.072–0.093) yields. The results obtained from the photolysis of the caged ester in different solvents indicated that solvent has influence on the rate of photorelease. Further, we also explored the ability of FPRPG, perylen-3-ylmethyl for the protection of alcohols and phenols.     

A practical and efficient procedure for reduction of carboxylic acids and their derivatives: use of KBH4-MgCl2

The use of KBH₄-MgCl₂ to reduce carboxylic acids and their derivatives to the corresponding alcohols or the respective reduced products is described. Methyl (S)-3,4-O-isopropylidene-3,4-dihydroxy butanoate 2 used as a reference substrate was reduced with KBH₄ and MgCl₂ in 1:1 mol ratio to (S)-1,2-O-isopropylidene-1,2,4-butanetriol 1.     

One-Pot Synthesis of Phenacyl Esters from Acetophenone, [Bmim]Br3, and Potassium Salts of Carboxylic Acids Under Solvent-Free Conditions

One-pot synthesis of phenacyl esters from acetophenone, [Bmim]Br₃, and potassium salts of carboxylic acids under solvent-free conditions gave the corresponding phenacyl esters with excellent yields.     

Preparation of N-protected allylic amines and α-methylene-β-amino acids from vinylalumination/Baylis-Hillman products via tandem SN2′ substitution-Overman rearrangement

S_N2′ reaction on the acetates obtained from vinylalumination or Baylis-Hillman products, followed by in situ reduction afforded allylic alcohols. Upon conversion to trichloroacetimidates and [3,3]-sigmatropic rearrangement, the corresponding N-protected β-substituted allylic amines were obtained in good yields. Utilization of hydroxy group as the nucleophile furnished allylic hydroxy esters, which were converted to protected α-methylene-β-amino acids via Overman rearrangement.     

Zirconium-catalyzed cyclopropanation of α-olefins mediated by R′CO2R″ and ClnAlEt3-n

A Cp₂ZrCl₂-catalyzed one-pot cyclopropanation method has been developed to afford alkoxycyclopropanes and cyclopropanols from α-olefins involving esters of carboxylic acids and Cl_nAlEt_3-n.     

Effective esterification of carboxylic acids using (6-oxo-6H-pyridazin-1-yl)phosphoric acid diethyl ester as novel coupling agents

(6-Oxo-6H-pyridazin-1-yl)phosphoric acid diethyl esters (3) are efficient and selective coupling agents for equimolar esterification of carboxylic acids and alcohols. Esterification of aliphatic and aromatic carboxylic acids with aliphatic and aromatic alcohols using 3 afforded the corresponding esters chemoselectively in good to excellent yield.     

Solvent-modulated chemoselective deprotections of trialkylsilyl esters and chemoselective esterifications

A series of trialkylsilyl esters were deprotected or transesterificated into their corresponding carboxylic acids or methyl esters under a catalytic amount of CBr₄ in alcohol reaction system. This method enables to desilylate secondary sp³-carbon, sp²-carbon, sp-carbon and aryl tethered trialkylsilyl esters to carboxylic acids, whereas primary sp³-carbon tethered trialkylsilyl esters were further converted into their methyl esters under CBr₄/MeOH reaction conditions. The highly chemoselective deprotections can be modulated and achieved by the introduced protecting trialkylsilyl groups and the used alcohols such as MeOH and EtOH under this photochemically-induced reaction conditions.     

Simple and Efficient Procedure for the Friedel–Crafts Acylation of Aromatic Compounds with Carboxylic Acids in the Presence of P2O5/AL2O3 Under Heterogeneous Conditions

An efficient and chemoselective method for the Friedel–Crafts acylation of aromatic compounds using P₂O₅/Al₂O₃ and carboxylic acids. Both aromatic and aliphatic carboxylic acids reacted easily to afford the corresponding aromatic ketones in good yields.     

Pyrolysis of Amino Acid Derived Stabilised Ylides as a Route to Chiral Acetylenic Amines and Amino Acids and Gaba Analogues

Abstract

We recently reported the pyrolysis of stabilised ylides as a method for overall conversion of carboxylic acids to homologous acetylenic esters and terminal alkynes.^1,2 This has now been applied successfully to amino acids. A wide range of alkoxycarbonyl protected amino acids have been converted to the stable crystalline ylides 1. These have been fully characterised, and upon FVP, eliminate Ph₃PO to afford the protected acetylenic amino acids 2 in good yield and without significant racemisation. Subsequent reactions of these extremely versatile intermediates have been used to gain access to a wide variety of chiral amine and amino acids of great interest as potential selective enzyme inhibitors and components for modified peptide structures.     

Friedel-Crafts acylation of aromatic compounds with carboxylic acids in the presence of P2O5/SiO2 under heterogeneous conditions

A convenient and efficient procedure for the Friedel-Crafts acylation of aromatic compounds with carboxylic acids in the presence of P₂O₅/SiO₂ is described. Both aromatic and aliphatic carboxylic acids reacted easily to afford the corresponding aromatic ketones. The use of non-toxic and inexpensive materials, simple and clean work-up, short reaction times and good yields of the products are the advantages of this method.     

Direct Esterification of Carboxylic Acids with Alcohols Catalyzed by Iron(III) Acetylacetonate Complex

Direct condensation of carboxylic acids and alcohols with electronic, steric, and functional group variations was carried out using the environmentally benign, moisture-stable, inexpensive, and recoverable iron(III) acetylacetonate [Fe(acac)₃] as catalyst (5 mol%). This iron salt efficiently catalyzed the esterification of several primary and secondary alcohols in refluxing xylene, without the need for a dehydration reagent. The chemoselectivity of the proposed protocol was demonstrated by the selective esterification of primary alcohol functionality in racemic 1-phenylethane-1,2-diol with benzoic acid. The esterification was also applicable to unmasked α -hydroxyacid, guasiaromatic, heterocyclic, and N-protected amino acids.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

AlCl3 · 6H2O/KI/CH3CN/H2O: An Efficient and Versatile System for Chemoselective C–O Bond Cleavage and Formation of Halides and Carbonyl Compounds from Alcohols in Hydrated Media

AlCl₃ · 6H₂O/KI/CH₃CN/H₂O, an efficient and versatile system, cleaves the C–O bonds of esters, acetals, ethers, and oxathiolanes to the corresponding acids, alcohols, and carbonyl compounds chemoselectively at 80 °C in hydrated media with good yields. This system also converts the alcohols (primary/secondary) to halides and oxidizes the alcohols (primary/secondary) to the corresponding carbonyl compounds in the presence of DMSO.     

Pd/Light‐Accelerated Atom‐Transfer Carbonylation of Alkyl Iodides: Applications in Multicomponent Coupling Processes Leading to Functionalized Carboxylic Acid Derivatives

The atom‐transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition‐metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C‐functionalization of alkenes was attained in which α‐substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three‐component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd‐dimer complex [Pd₂(CNMe)₆][PF₆]₂, which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three‐ or four‐component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.     

Polystyrylsulfonyl-3-nitro-1H-1,2,4-triazolide-resin: a new solid-supported reagent for the esterification of amino acids

We describe the application of the polystyrylsulfonyl-3-nitro-1H-1,2,4-triazolide-resin, readily available from the corresponding commercially available polystyryl sulfonyl chloride resin, to the solution-phase synthesis of esters from protected α-amino acids and alcohols in high yields and purity with a low level of racemisation of the amino acids. All by-products can be removed by filtration and extraction.     

Efficient photolytic esterification of carboxylic acids with alcohols in perhalogenated methane

Condensation of carboxylic acids and alcohols to give esters was accomplished with selectivity under photolytic conditions in 66-99% yields by use of CCl₄ or BrCCl₃ at room temperature.