Ligand-Promoted RhI-Catalyzed C2-Selective C−H Alkenylation and Polyenylation of Imidazoles with Alkenyl Carboxylic Acids

The first Rh^I-catalyzed, directed decarbonylative C2−H alkenylation of imidazoles with readily available alkenyl carboxylic acids is reported. The reaction proceeds in a highly regio- and stereoselective manner, providing efficient access to C2-alkenylated imidazoles that are generally inaccessible by known C−H alkenylation methods. This transformation accommodates a wide range of alkenyl carboxylic acids, including challenging conjugated polyene carboxylic acids, and diversely decorated imidazoles with high functional group compatibility. The presence of a removable pyrimidine directing group and the use of a bidentate phosphine ligand are pivotal to the success of the catalytic reaction. This process is also suitable for benzimidazoles. Importantly, the scalability and diversification of the products highlight the potential of this protocol in practical applications. Detailed experimental and computational studies provide important insights into the underlying reaction mechanism.     

Boron-Catalyzed α-Functionalizations of Carboxylic Acids

Catalytic, chemoselective, and asymmetric α-functionalizations of carboxylic acids promise up-grading simple feedstock materials to value-added functional molecules, as well as late-stage structural diversifications of multifunctional molecules, such as drugs and their leads. In this personal account, we describe boron-catalyzed α-functionalizations of carboxylic acids developed in our group (five reaction types). The reversible boron carboxylate formation is key to the acidification of the α-protons and enolization using mild organic bases, allowing for chemoselective and asymmetric bond formations of carboxylic acids. The ligand effects on reactivity and stereoselectivity, substrate scopes, and mechanistic insights are summarized.     

The Influence of Weakly Coordinating Cations on the O−H⋅⋅⋅O− Hydrogen Bond of Silanol-Silanolate Anions

The reaction of a saline phosphazenium hydroxide hydrate with siloxanes led to a novel kind of silanol-silanolate anions. The weakly coordinating behavior of the cation renders the formation of silanol-silanolate hydrogen bonds possible, which otherwise suffer from detrimental silanolate–oxygen cation interactions. We investigated the influence of various weakly coordinating cations on silanol-silanolate motifs, particularly with regard to different cation sizes. While large cations favor the formation of intramolecular hydrogen bonds resulting in cyclic structures, the less bulky tetramethyl ammonium cation encourages the formation of polyanionic silanol-silanolate chains in the solid state.     

Polyenolates of Unsaturated Carboxylic Acids in Synthesis. Synthesis of Unsaturated α-Amino Acids and β-Hydrazing Acids

Regioselective reaction of lithium diene-and triene-diolates 1 and 2 with O-diphenylphosphinyl hydroxylamine affords unsaturated α-amino acids 3 and 4. Addition to DEAD leads selectively to γ-hydrazino unsaturated acids 5 and 6.     

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.     

A−H…σ Hydrogen Bonds: Dihydrogen and Cycloalkanes as Proton Acceptors

ωB97XD/aug-cc-pVTZ calculations were performed for complexes of dihydrogen, cyclopropane, cyclobutane and cyclopentane, with simple proton donating species such as hydrogen fluoride, hydrogen chloride, water, hydrogen cyanide and acetylene. Numerous dependencies between geometrical, energetic and topological parameters of complexes considered were found, since various theoretical approaches were applied: Quantum Theory of ‘Atoms in Molecules’ (QTAIM), Natural Bond Orbital (NBO) method and energy decomposition analysis (EDA). It was confirmed that complexes of dihydrogen and cyclopropane are linked through the A−H…σ interactions that may be classified as hydrogen bonds. In the case of complexes of cyclobutane such hydrogen bonds are rather weak. Other type and also weak A−H…C hydrogen bonds are formed for complexes with cyclopentane.     

Ligand-Enabled Auxiliary-Free meta-C−H Arylation of Phenylacetic Acids

The meta-C−H arylation of free phenylacetic acid was realized using 2-carbomethoxynorbornene (NBE-CO₂Me) as a transient mediator. Both the modified norbornene and the mono-protected 3-amino-2-hydroxypyridine type ligand are crucial for this auxiliary-free meta-C−H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta-arylated products in high yields.     

Facile Synthesis of Alkylidene Phthalides by Rhodium-Catalyzed Domino C−H Acylation/Annulation of Benzamides with Aliphatic Carboxylic Acids

The Rh-catalyzed ortho-C(sp²)−H functionalization of 8-aminoquinoline-derived benzamides with aliphatic acyl fluorides generated in situ from the corresponding acids has been developed. This reaction initiated with 8-aminoquinoline-directed ortho-C(sp²)−H acylation, which was accompanied by subsequent intramolecular nucleophilic acyl substitution of amide group to produce alkylidene phthalides This approach exhibits high stereo-selectivity for Z-isomer products, and tolerates a variety of functional groups as well as aliphatic carboxylic acids with diverse structural scaffolds.     

Distal γ-C(sp3)−H Olefination of Ketone Derivatives and Free Carboxylic Acids

Reported herein is the distal γ-C(sp³)−H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino-acid directing group and using the ligand combination of a mono-N-protected amino acid (MPAA) and an electron-deficient 2-pyridone were critical for the γ-C(sp³)−H olefination of ketone substrates. In addition, MPAAs enabled the γ-C(sp³)−H olefination of free carboxylic acids to form diverse six-membered lactones. Besides alkyl carboxylic acids, benzylic C(sp³)−H bonds also could be functionalized to form 3,4-dihydroisocoumarin structures in a single step from 2-methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ-C(sp³)−H olefinated products.     

Selective Esterification of Aliphatic Carboxylic Acids in the Presence of Aromatic Carboxylic Acids Over Monoammonium Salt of 12‐Tungstophosphoric Acid

Monoammonium salt of 12‐tungstophosphoric acid [(NH₄)H₂PW₁₂O₄₀] was found to be a practical and useful heterogeneous catalyst for an efficient and selective esterification of aliphatic carboxylic acids with alcohols in the presence of aromatic carboxylic acids. The heteropoly acid–based heterogeneous catalyst has the advantages of a simple workup procedure, water insolubility, and good activity.     

α‐Chlorination of Carboxylic Acids Using Trichloroisocyanuric Acid

Abstract

Carboxylic acids are chlorinated in the α position by heating with trichloroisocyanuric acid after formation of a small amount of the acid chloride using phosphorus trichloride.     

σ-Holes in Iodonium Ylides: Halogen-Bond Activation of Carboxylic Acids,Phenols and Thiophenols May Enable Their X−H Insertion Reactions

The first systematic evaluation of the electrostatic potential energy maps of iodonium ylides was conducted. We determined that they possess two σ-holes of differing electron deficiencies, with the more electropositive σ-hole located opposite the dative I−C bond to the β-dicarbonyl motif, and the lesser electropositive σ-hole located opposite the iodoarene C−I bond. We also conducted the first systematic evaluation of carboxylic acids, phenols and thiophenols in the O/S-alkylation reaction of iodonium ylides. While carboxylic acids and thiophenols were found to be generally viable, only phenols possessing electron-withdrawing substituents were effective. This high-yielding and highly chemoselective reaction is believed to involve halogen-bond activation of heteroatoms, and nicely complements existing diazo-based methods for alkylation of acidic functional groups.     

Reduction and N-Alkylation of α-Methylene-indolines with Sodium Cyanoborohydride in Carboxylic Acids

The reaction of α-methylene-indolines with NaCNBH₃ in carboxylic acids at room temperature can yield either 2β,3β-dihydro-indolines or their N-alkyl derivatives as main products with high selectivity, depending mainly on the carboxylic acid and on the reaction time when using a large excess of NaCNBH₃.     

The Emergence of Palladium-Catalyzed C(sp3)−H Functionalization of Free Carboxylic Acids

Palladium-catalyzed directing group assisted C−H bond activation has emerged as a powerful tool in synthetic organic chemistry. However, only recently, among various directing groups, widely available carboxylate moiety is recognized as a versatile candidate for the regioselective transformations. Notably, palladium-catalyzed carboxylate directed C(sp³)−H bond activation and diverse functionalization is highly challenging and has gained huge attention for its versatile applications. Mono- and bidentate ligands have proven to be useful for accelerating the C(sp³)−H bond activation step, which helps to control reactivity and selectivity (including enantioselectivity). In this Minireview, we discuss the recent progress made in palladium-catalyzed C(sp³)−H bond functionalization reactions for the construction of C−C and C−Heteroatom bonds with the direction of free carboxylic acid.     

Esterification of Carboxylic Acids and Diacids by Trialkyl Borate under Solvent- and Catalyst-Free Conditions

Esterification or transesterification reactions are usually carried out in the presence of homogeneous or heterogeneous catalysts. However, recently a new method was reported for the esterification of carboxylic acids by tributyl borate under solvent- and catalyst-free conditions. In order to show the synthetic ability of trialkyl borate esters in the esterification reactions, here, the esterification of other carboxylic acids and diacids by tributyl-, triisoamyl-, and tribenzyl borate under the same conditions were reported. Some of the prepared ester and diester products have found wide applications as plasticizers and synthetic ester base lubricants. The esterification reactions have been cleanly carried out in the absence of any solvent under catalyst-free conditions. The maximum rate belongs to isoamyl trichloroacetate （VIb） which reached about 76% within about 6.5 h. On the basis of obtained findings, it seems that electron withdrawing groups on carboxylic acid facilitate the esterification reaction.     

Transition Metal-Free Aromatic C−H,C−N,C−S and C−O Borylation

Aromatic organoboron compounds are highly valuable building blocks in organic chemistry. They were mainly synthesized through aromatic C−H and C−Het borylation, in which transition metal-catalysis dominate. In the past decade, with increasing attention to sustainable chemistry, numerous transition metal-free C−H and C−Het borylation transformations have been developed and emerged as efficient methods towards the synthesis of aromatic organoboron compounds. This account mainly focuses on recent advances in transition metal-free aromatic C−H, C−N, C−S, and C−O borylation transformations and provides insights to where further developments are required.     

Cooperative Effects between Chiral Cpx–Iridium(III) Catalysts and Chiral Carboxylic Acids in Enantioselective C−H Amidations of Phosphine Oxides

An enantioselective C−H amidation of phosphine oxides by using an iridium(III) catalyst bearing an atropchiral cyclopentadienyl (Cp^x) ligand is reported. A very strong cooperative effect between the chiral Cp^x ligand and a phthaloyl tert-leucine enabled the transformation. Matched–mismatched cases of the different acid enantiomers are shown. The amidated P-chiral arylphosphine oxides are formed in yields of up to 95 % and with excellent enantioselectivities of up to 99:1 er. Enantiospecific reduction provides access to valuable P-chiral phosphorus(III) compounds.     

Ammonium Iodide–Promoted Cyclization of Aryl-Substituted Carboxylic Acids

An efficient procedure was developed for direct preparation of aryl-substituted lactones from corresponding aryl carboxylic acids, which was promoted by ammonium iodide. In this protocol, aryl carboxylic acids were treated with ammonium iodide, potassium bromide, and oxidant Oxone in a mixture of acetonitrile and 2,2,2-trifluoroethanol (6:4) at room temperature for 12 h, resulting in corresponding aryl lactones in moderate to good yields.     

α-Hydroxylation of Carboxylic Acids and Amides Using Bis(Trimethylsilyl)Peroxide

Bis(trimethylsilyl)peroxide is shown to react with enolate anions derived from carboxylic acids and amides to give the corresponding α-hydroxy derivatives.     

Efficient and Rapid Method for the Oxidation of Electron‐Rich Aromatic Aldehydes to Carboxylic Acids Using Improved Basic Hydrogen Peroxide

An efficient and rapid method for oxidation of electron‐rich aromatic aldehydes to their corresponding carboxylic acids in excellent yields was developed. It is based on the oxidation of methoxy‐substituted benzaldehydes in methanol with an improved aqueous basic hydrogen peroxide system. Benzaldehydes with electron‐withdrawing substituents are oxidized to the corresponding carboxylic acid in excellent yields under mild reaction conditions.