Deoxygenative Arylation of Carboxylic Acids by Aryl Migration

An unprecedented deoxygenative arylation of aromatic carboxylic acids has been achieved, allowing the construction of an enhanced library of unsymmetrical diaryl ketones. The synergistic photoredox catalysis and phosphoranyl radical chemistry allows for precise cleavage of a stronger C−O bond and formation of a weaker C−C bond by 1,5-aryl migration under mild reaction conditions. This new protocol is independent of substrate redox-potential, electronic, and substituent effects. It affords a general and promising access to 60 examples of synthetically versatile o-amino and o-hydroxy diaryl ketones under redox-neutral conditions. Furthermore, it also brings one concise route to the total synthesis of quinolone alkaloid, (±)-yaequinolone A2, and a viridicatin derivative in satisfying yields.     

Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions

A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups. The late-stage functionalization of carboxylic acid active pharmaceutical ingredients and pharmaceutically relevant compounds is also discussed.     

Ligand‐Free Palladium‐Catalyzed Aerobic Oxidative Coupling of Carboxylic Anhydrides with Arylboronic Acids

We report a new, effective and environmentally friendly protocol for selective aerobic oxidative coupling of arylboronic acids with carboxylic anhydrides in the presence of ligand‐free palladium catalyst. The aryl benzoates are obtained in good to excellent yields.     

Beyond Kolbe and Hofer–Moest: Electrochemical Synthesis of Carboxylic Anhydrides from Carboxylic Acids

Herein we report a conceptually new non‐decarboxylative electrolysis of carboxylic acids to obtain their corresponding anhydrides as highly valuable reagents in organic synthesis. All carbon atoms of the starting material are preserved in the product in an overall redox‐neutral reaction. In a broad substrate scope of carboxylic acids the anhydrides are generated with high selectivity, which demonstrates the versatility of the developed method. Beneficially, no dehydrating reagents are required in comparison to conventional methods and the synthesis is based on uncritical starting materials using graphite and stainless steel as very inexpensive and eco‐friendly electrode materials.     

镍催化的芳基硼酸偕二氟炔丙基化反应

偕二氟炔丙基取代的芳烃是一类非常重要的化合物, 但传统合成该类化合物的方法却存在很大局限性. 以过渡金属催化直接向芳烃偕二氟炔丙基化是一种高效简洁制备上述化合物的方法. 以廉价易得的Ni(NO₃)₂·6H₂O为催化剂, 首次实现了镍催化下芳基硼酸与α,α-二氟炔丙基溴的偶联反应. 该反应不仅温和高效、原料廉价易得、官能团兼容性良好, 而且还能进行克量级放大和对生物活性分子的后期氟修饰, 从而为新药研发提供了一种有效手段.     

Efficient Synthesis of Aromatic Carboxylic Acids from Aryl Ketones in Ionic Liquid

Conversion of aryl ketones to the corresponding aromatic carboxylic acids has been achieved using sequential treatment of HDNIB and urea–hydrogen peroxide in [bmim]BF₄ ionic liquid.     

Pd-Catalyzed Difluoromethylations of Aryl Boronic Acids,Halides, and Pseudohalides with ICF2H Generated ex Situ

An expedient ex-situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd-catalyzed difluoromethylation of aryl boronic acids and ester derivatives in a two-chamber reactor is reported. Heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane proved to be effective for the generation of near stoichiometric amounts of DFIM for the ensuing catalytic coupling step. A two-step difluoromethylation of aryl (pseudo)halides with tetrahydroxydiboron as a low-cost reducing agent, both promoted by Pd catalysis, proved effective to install this fluorine-containing C₁ group onto several pharmaceutically relevant molecules. Finally, the method proved adaptable to deuterium incorporation by simply adding D₂O to the DFIM-generating chamber.     

Biaryl and Aryl Ketone Synthesis via Pd‐Catalyzed Decarboxylative Coupling of Carboxylate Salts with Aryl Triflates

A bimetallic catalyst system has been developed that for the first time allows the decarboxylative cross‐coupling of aryl and acyl carboxylates with aryl triflates. In contrast to aryl halides, these electrophiles give rise to non‐coordinating anions as byproducts, which do not interfere with the decarboxylation step that leads to the generation of the carbon nucleophilic cross‐coupling partner. As a result, the scope of carboxylate substrates usable in this transformation was extended from ortho‐substituted or otherwise activated derivatives to a broad range of ortho‐, meta‐, and para‐substituted aromatic carboxylates. Two alternative protocols have been optimized, one involving heating the substrates in the presence of Cu^I/1,10‐phenanthroline (10–15 mol %) and PdI₂/phosphine (2–3 mol %) in NMP for 1–24 h, the other involving Cu^I/1,10‐phenanthroline (6–15 mol %) and PdBr₂/Tol‐BINAP (2 mol %) in NMP using microwave heating for 5–10 min. While most products are accessible using standard heating, the use of microwave irradiation was found to be beneficial especially for the conversion of non‐activated carboxylates with functionalized aryl triflates. The synthetic utility of the transformation is demonstrated with 48 examples showing the scope and limitations of both protocols. In mechanistic studies, the special role of microwave irradiation is elucidated, and further perspectives of decarboxylative cross‐couplings are discussed.     

Palladium‐Catalyzed Synthesis of (Hetero)Aryl Alkyl Sulfones from (Hetero)Aryl Boronic Acids,Unactivated Alkyl Halides,and Potassium Metabisulfite

A palladium‐catalyzed one‐step synthesis of (hetero)aryl alkyl sulfones from (hetero)arylboronic acids, potassium metabisulfite, and unactivated or activated alkylhalides is described. This transformation is of broad scope, occurs under mild conditions, and employs readily available reactants. A stoichiometric experiment has led to the isolation of a catalytically active dimeric palladium sulfinate complex, which was characterized by X‐ray diffraction analysis.     

Supported Palladium-Catalyzed Carbonylative Synthesis of Diaryl Ketones from Aryl Bromides and Arylboronic Acids

A palladium supported on graphitic carbon nitride (Pd/g-C₃N₄) catalyzed carbonylative reaction of aryl bromides and arylboronic acids by has been developed for the construction of diaryl ketones. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various diaryl ketones in moderate to good yields.     

Catalytic Ketonization of Carboxylic Acids Synthesis of Saturated and Unsaturated Ketones

Activity of 20wt% MO₂/Al₂O₃ catalysts, where M = Mn, Ce and Zr has been studied in ketonisation of the mixtures of propanoic/pentanoic, ethanoic/10-undecenoic and hexanoic/(Z)-9-octadecenoic (oleic) acids. Irrespective of the molecular weights and molar ratios of reacting acids, high yields of ketones were obtained over Mn and Ce oxide catalysts at approximately 673 K. Isomerization of C=C double bonds and partial pyrolysis occurred during catalytic ketonization of 10-undecenoic and oleic acids, diminishing slightly the yield of ketones. The preparation of (Z)-14-tricosen-6-one has been performed, being the starting material for the synthesis of (Z)-9-tricosene - sex attractant of male house fly.     

Highly Chemoselective and Versatile Method for Direct Conversion of Carboxylic Acids to Ketones Utilizing Zinc Ate Complexes

Various carboxylic acids were directly transformed into the corresponding ketones by utilizing organozinc ate complexes, which provide high chemoselectivity without any overreaction to the undesired tertiary carbinol, owing to formation of a stable tetrahedral zincioketal intermediate. This method offers good overall atom/step/pot economy and operational simplicity.     

Boronic Acid Catalysis for Mild and Selective [3+2] Dipolar Cycloadditions to Unsaturated Carboxylic Acids

Herein, the concept of boronic acid catalysis (BAC) for the activation of unsaturated carboxylic acids is applied in several classic dipolar [3+2] cycloadditions involving azides, nitrile oxides, and nitrones as partners. These cycloadditions can be used to produce pharmaceutically interesting, small heterocyclic products, such as triazoles, isoxazoles, and isoxazolidines. These cycloadducts are formed directly and include a free carboxylic acid functionality that can be employed for further transformations, thereby avoiding prior masking or functionalization. In all cases, BAC provides faster reactions, under milder conditions, with much improved product yields and regioselectivities. In some instances, such as triazole formation from the reaction of azides with 2‐alkynoic acids, catalysis with ortho‐nitrophenylboronic acid circumvents the undesirable product decarboxylation observed when using thermal activation. By using NMR spectroscopic studies, the boronic acid catalyst was shown to provide activation by a LUMO‐lowering effect in the unsaturated carboxylic acid, likely via a monoacylated hemiboronic ester intermediate.     

钯催化的酸酐C-O键的活化及反应

综述了钯催化的酸酐碳—氧键的活化和反应 ,及由羧酸直接制备相应的醛、酮且不需要卤原子和碱参与的方法     

Enantioselective 1,4‐Addition Reaction of α,β‐Unsaturated Carboxylic Acids with Cycloalkanones Using Cooperative Chiral Amine–Boronic Acid Catalysts

An enantioselective 1,4‐addition of α,β‐unsaturated carboxylic acids with cycloalkanones has been developed by using chiral amine–boronic acid cooperative catalysts. In the presence of a chiral amine and boronic acid, cycloalkanones and carboxylic acids are activated as chiral enamines and mixed anhydrides, respectively. The corresponding 1,4‐adducts are obtained in high yield with high enantioselectivity. Furthermore, subsequent oxylactonization of the 1,4‐adducts gives spirolactones with high diastereoselectivity.