Triflylpyridinium Enables Rapid and Scalable Controlled Reduction of Carboxylic Acids to Aldehydes using Pinacolborane

Building up new and efficient methods for the controlled conversion of carboxylic acids to aldehydes is important. Herein, we report a rapid, modular and scalable method for the conversion of carboxylic acids to aldehydes using pinacolborane at ambient temperature, in which a triflylpyridinium reagent is used. The conversion of carboxylic acid to intermediate acylpyridinium by triflylpyridinium is new. A binary pyridine-coordinated boronium complex is generated after reduction. The unprecedented reduction of the acylpyridinium by HBpin opens up a practically direct synthesis of aldehydes from carboxylic acids. Theoretical studies indicate that the reduction of acylpyridinium requires a lower activation free energy than that of the product aldehyde. The synthetic advantage of this protocol is further highlighted by the scalable synthesis of aldehyde via continuous flow process. Configuration retention for chiral acids are presented in those syntheses.     

A general procedure for the esterification of carboxylic acids with diazoalkanes generated in situ by the oxidation of N-tert-butyldimethylsilylhydrazones with (difluoroiodo)benzene

The bimolecular reaction of carboxylic acids with diazoalkanes to form esters is among the mildest and most efficient of organic transformations but is seldom used in synthesis beyond the important case of methyl esterification. This is largely a consequence of the inaccessibility and poor stability of higher diazoalkanes as substrates. In this work we describe a new method for the synthesis of diazoalkanes by the oxidation of N-tert-butyldimethylsilylhydrazones (TBSHs) with (difluoroiodo)benzene, a reagent heretofore unexplored in the context of hydrazone oxidation. When conducted in the presence of a carboxylic acid substrate, the oxidation leads to efficient esterification in situ. In addition to greatly extending the range of diazoalkanes that are now available for esterifications, this new protocol offers significant advantages with regard to safety, for diazo intermediates are neither isolated nor achieve appreciable concentrations during the reaction.     

Direct Transformation of Esters into Arenes with 1,5‐Bifunctional Organomagnesium Reagents

A direct transformation of carboxylic acid esters into arenes with 1,5‐bifunctional organomagnesium reagents is described. This efficient and practical method enables the one‐step defunctionalization of various carboxylic acid esters to prepare benzene, anthracene, tetracene, and pentacene derivatives. A double nucleophilic addition of the 1,5‐organodimagnesium reagent to the ester is followed by an immediate 1,4‐elimination reaction that leads to the direct [5+1] formation of a new aromatic ring.     

Dimethylsulfoxide-iodine catalysed deprotection of allyl carboxylic esters

A convenient method for deprotection of allyl carboxylic esters has been developed by using the inexpensive and environmentally friendly reagent dimethylsulfoxide-iodine. A variety of carboxylic esters were deprotected to the carboxylic acids. This method is more efficient and operationally simple in comparison to methods using transition metal complexes.     

Selective Esterification Reaction Involving Hexaalkyl Guanidinium Chloride Catalyst

A new efficient and selective esterification reaction of carboxylic acids with chloroformates is described using silica-supported catalyst (PBGSiCl). The chemioselectivity of the reaction was high particularly for sterically hindered carboxylic acids supported by a single pathway reaction.     

Effective synthesis of 1beta-acyl glucuronides by selective acylation

[reaction: see text] Acyl glucuronides are vital metabolites for many carboxylic acid containing drugs. We report an efficient new method for the chemical synthesis of these molecules by selective 1beta-acylation of allyl glucuronate with carboxylic acids catalyzed by HATU and then mild deprotection through treatment with Pd(PPh(3))(4) and morpholine. The method is effective for a range of aryl and alkyl carboxylic acids, including important drugs.     

Copper-catalyzed synthesis of aromatic carboxylic acids from arylboronic acids and acetyl acetate

A simple and efficient copper-catalyzed method for the synthesis of aromatic carboxylic acids in moderate to high yields with great functional-group compatibility in the substrates has been developed. The new method uses readily available arylboronic acids and acetyl acetate as the starting materials and inexpensive CuI as the catalyst.     

微波辅助酸催化水相一锅高效合成吖啶酸

本文建立一种以去离子水为溶剂,在微波辅助酸催化下一锅串联高效合成吖啶酸的新方法,该反应条件温和、操作简单、绿色高效。在优化反应条件下考察了多种取代基团对反应的影响,结果显示该方法具有良好的适应性,以83%～97%收率得到18个吖啶酸化合物。所有化合物结构均经过¹H NMR、¹³C NMR、HRMS、熔点等表征确认。     

A novel method for the one-pot conversion of carboxylic acids to N,N-dimethylamides

A simple, efficient, and new method has been developed for the preparation of N,N-dimethylamides from carboxylic acids. As described below, treatment of a variety of aromatic carboxylic acids with N,N-dimethylsulfamoyl imidazole or N,N-dimethylsulfamoyl chloride in the presence of a mixture of methanesulfonic acid/phosphorus pentoxide (2:1, v/w) proceeded effectively to afford the corresponding N,N-dimethylamides in moderate to good yields. This method is easy, rapid, and good yielding for the synthesis of N,N-dimethylamides from carboxylic acids.     

Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Abeta-peptide aggregation inhibitors

A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on Abeta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer Abeta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric Abeta-peptide.     

Graphene oxide (GO) catalyzed transamidation of aliphatic amides: An efficient metal-free procedure

Transamidation involves direct interconversion of an amide with amine, and represents an alternative to the common method of amide formation from the reaction of carboxylic acid with an amine. While the carboxamides have huge potential in biological systems and polymer industries, their formation from carboxylic acids requires activation by a suitable catalyst. A metal-free transamidation of aliphatic amide with aromatic amine catalyzed by graphene oxide (GO) has been developed and established as a general, synthetically useful and selective procedure. Graphene oxide bearing several carboxylic acids on the edges and having large surface area acts as an efficient and recyclable catalyst for transamidation.     

Direct, facile synthesis of acyl azides and nitriles from carboxylic acids using bis(2-methoxyethyl)aminosulfur trifluoride

A mild, efficient, and practical method for the one-step synthesis of acyl azides from carboxylic acids using bis(2-methoxyethyl)aminosulfur trifluoride is described. The reaction was easily extended to the synthesis of the corresponding nitriles by the inclusion of phosphorous reagents. The method can be applied to the synthesis of optically active nitriles in high yields, and is compatible with fluorous phosphines.     

Copper-catalyzed aerobic oxidative synthesis of aromatic carboxylic acids

A simple, practical and efficient copper-catalyzed method for synthesis of aromatic carboxylic acids has been developed. The protocol uses inexpensive CuI/L-proline as the catalyst/ligand, and readily available aryl halides and malononitrile as the starting materials, and the corresponding aromatic carboxylic acids were obtained in moderate to good yields. The method is of tolerance towards functional groups in the substrates.     

SbCl5-wet acetonitrile: a new system for chemoselective O-desilylation

A new efficient method for deprotection of TBDMS derivatives of phenols, primary alcohols, carboxylic acids and secondary amines, consisting of SbCl₅ and MeCN with 0.1% water (w/v), is reported. It effects inter alia desilylation of a CH₂OTBDMS group in the presence of a ketal function.     

New method for preparation of anhydrides and amides of carboxylic acids using carbon tetrachloride

Conclusions A new efficient method was proposed for the preparation of the anhydrides and amides of carboxylic acids in 30–97% yield, which is based on the reaction of carboxylic acids (their alkali-metal salts) with CCl₄, or with CCl₄, and an amide, in the presence of copper or iron salts.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 220–223, January, 1978.     

A novel and efficient procedure for the preparation of allylic alcohols from α,β-unsaturated carboxylic esters using LiAlH4/BnCl

A new and efficient method for the reduction of α,β-unsaturated carboxylic esters to allylic alcohols utilizing LiAlH₄/BnCl is described. Various α,β-unsaturated esters, including the coumarins bearing α,β-unsaturated lactone skeleton, can be converted smoothly into their corresponding allylic alcohols in high yields under mild conditions with short reaction times.     

A convenient method for the preparation of inverted tert-alkyl carboxylates from chiral tert-alcohols by a new type of oxidation-reduction condensation using 2,6-dimethyl-1,4-benzoquinone

Oxidation-reduction condensation using in situ-formed alkoxydiphenylphosphines, 2,6-dimethyl-1,4-benzoquinone, and carboxylic acids provided a new and efficient method for the preparation of inverted tert-alkyl carboxylates from various chiral tertiary alcohols.     

Kinetic Resolution of Racemic Secondary Benzylic Alcohols by the Enantioselective Esterification Using Pyridine‐3‐carboxylic Anhydride (3‐PCA) with Chiral Acyl‐Transfer Catalysts

Pyridine‐3‐carboxylic anhydride (3‐PCA) was found to function as an efficient coupling reagent for the preparation of carboxylic esters from various carboxylic acids with alcohols under mild conditions by a simple experimental procedure. This novel condensation reagent 3‐PCA was applicable not only for the synthesis of achiral carboxylic esters catalyzed by 4‐(dimethylamino)pyridine (DMAP) but also for the production of chiral carboxylic esters by the combination of chiral nucleophilic catalyst, such as tetramisole (=2,3,5,6‐tetrahydro‐6‐phenylimidazo[2,1‐b][1,3]thiazole) derivatives. An efficient kinetic resolution of racemic benzylic alcohols with achiral carboxylic acids was achieved by using 3‐PCA in the presence of (R)‐benzotetramisole ((R)‐BTM), and a variety of optically active carboxylic esters were produced with high enantiomeric excesses by this new chiral induction system without using a tertiary amine.     

Esterification of sterically hindered pyrrole carboxylic acids using dimethyl and diethyl sulfate under mild basic conditions

A simple and efficient method for the esterification of sterically hindered pyrrole carboxylic acids using dialkylsulfate and anhydrous potassium carbonate is described.     

Recyclable hypervalent iodine(III) reagent iodosodilactone as an efficient coupling reagent for direct esterification, amidation, and peptide coupling

A hypervalent iodine(III) reagent plays a novel role as an efficient coupling reagent to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization. The regeneration of iodosodilactone (1) can also be readily achieved. The intermediate acyloxyphosphonium ion C from the activation of a carboxylic acid is thought to be involved in the present esterification reaction.