Palladium‐Catalyzed Heck‐Type Reactions of Allylic Esters with Arylboronic Acids or Potassium Aryltrifluoroborates

A selective and general route to (E)‐1,3‐diaryl‐prop‐1‐enes and (E)‐3‐arylallyl acetates has been developed by palladium‐catalyzed Heck‐type reactions of allylic esters with arylboronic acids or potassium aryltrifluoroborates. The present method selectively proceeds including β‐OAc elimination or β‐H elimination on the basis of the boronic acids. Whereas a variety of allylic esters were reacted with arylboronic acids, palladium(II) acetate [Pd(OAc)₂], tetra(n‐butyl)ammonium chloride [(n‐Bu)₄NCl] and postassium dihydrogen phosphate (KH₂PO₄) to afford the corresponding diarylation products in moderate to good yields, treatment of allylic esters with potassium aryltrifluoroborates furnished the corresponding monoarylation products.     

Recyclable Solid Ruthenium Catalysts Supported on Metal Oxides for the Addition of Carboxylic Acids to Terminal Alkynes

Ceria‐supported ruthenium catalysts (Ru/CeO₂) were found to be quite effective for the addition of various carboxylic acids to terminal alkynes, which gave the corresponding enol esters in moderate to high yields. The major products of the reaction were E‐isomers of anti‐Markovnikov adducts. Among the ceria‐supported ruthenium catalysts examined, those prepared using ruthenium precursors with chloride ligands showed high activities. The zirconia‐supported ruthenium catalyst (Ru/ZrO₂) showed activity comparable to that of the ceria‐supported catalyst. These catalysts were recyclable without a significant loss of activity, and the leaching of ruthenium species into the liquid phase was negligible after cooling the reaction mixture, which indicates marked superiority of the present solid oxide catalysts to conventional homogeneous catalysts.     

Characterization of Carboxylic Acid Reductases for Biocatalytic Synthesis of Industrial Chemicals

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids into aldehydes, which can serve as common biosynthetic precursors to many industrial chemicals. This work presents the systematic biochemical characterization of five carboxylic acid reductases from different microorganisms, including two known and three new ones, by using a panel of short‐chain dicarboxylic acids and hydroxy acids, which are common cellular metabolites. All enzymes displayed broad substrate specificities. Higher catalytic efficiencies were observed when the carbon chain length, either of the dicarboxylates or of the terminal hydroxy acids, was increased from C₂ to C₆. In addition, when substrates of the same carbon chain length are compared, carboxylic acid reductases favor hydroxy acids over dicarboxylates as their substrates. Whole‐cell bioconversions of eleven carboxylic acid substrates into the corresponding alcohols were investigated by coupling the CAR activity with that of an aldehyde reductase in Escherichia coli hosts. Alcohol products were obtained in yields ranging from 0.5 % to 71 %. The de novo stereospecific biosynthesis of propane‐1,2‐diol enantiomer was successfully demonstrated with use of CARs as the key pathway enzymes. E. coli strains accumulated 7.0 mm (R)‐1,2‐PDO (1.0 % yield) or 9.6 mm (S)‐1,2‐PDO (1.4 % yield) from glucose. This study consolidates carboxylic acid reductases as promising enzymes for sustainable synthesis of industrial chemicals.     

Highly Efficient Solvent‐Free Condensation of Carboxylic Acids with Alcohols Catalysed by Zinc Perchlorate Hexahydrate,Zn(ClO4)2⋅6 H2O

Zinc perchlorate hexahydrate, Zn(ClO₄)₂⋅6 H₂O, efficiently catalyses the esterification between nearly equimolar amounts of carboxylic acids and alcohols. The reaction works under solvent‐free conditions at relatively low temperatures. Excellent results were obtained with a wide range of substrates.     

Highly Efficient Direct Carboxylation of Propane into Butyric Acids Catalyzed by Vanadium Complexes

A direct and highly efficient carboxylation of propane by carbon monoxide into butyric acids (mainly isobutyric and, in a smaller amount, n‐butyric), in the presence of potassium peroxodisulphate (K₂S₂O₈) and in trifluoroacetic acid solution, has been achieved by using a vanadium catalytic system based on Ca[V{ON(CH(CH₃)COO)₂}₂] (synthetic amavadine), its model compounds Ca[V{ON(CH₂COO)₂}₂] or [VO{N(CH₂CH₂O)₃}] – other simpler vanadium compounds, such as [VO(acac)₂] or VOSO₄, are less active. Overall yields (based on propane) of carboxylic acids up to 70 % and TON values up to 18.4×10³ have been reached. The effects of various factors such as the propane and carbon monoxide pressures, temperature, time, catalyst amount and radical traps have been investigated, the reactions are shown to proceed via both C‐ and O‐centred radicals, with K₂S₂O₈ playing the role of an oxidant via a free radical mechanism.     

Fatty Acids from a Glass Sponge <Emphasis Type="Italic">Aulosaccus</Emphasis> sp. Occurrence of New Cyclopropane-Containing and Methyl-Branched Acids

In order to identify new structures, the free fatty acids from an extract of a glass sponge Aulosaccus sp. (from the north‐west Pacific) belonging to one of the least chemically investigated classes (Hexactinellida), were fractionated by RP‐HPLC and analyzed by NMR spectroscopy and GC–MS of their pyrrolidine derivatives, methyl(ethyl) esters and their dimethyl disulfide adducts. One hundred and twenty‐three C₁₂–C₃₁ acids (including nine new compounds) were detected, one hundred and ten of these compounds have not been found previously in glass sponges. The levels of common methylene‐interrupted polyenes, monoenes of the (n–7) family and less common branched‐chain components proved to be high. New acids were shown to be 5,13‐dimethyl‐tetradec‐4‐enoic, cis‐10,11‐methylene‐heptadecanoic, 10,12‐dimethyl‐octadecanoic, cis‐12,13‐methylene‐nonadecanoic, (14E)‐13‐methyl‐eicos‐14‐enoic, 19‐methyl‐eicos‐13‐enoic, cis‐20,21‐methylene‐heptacosanoic, 27‐methyl‐octacos‐21‐enoic and (22Z)‐nonacos‐22‐enoic. Some important mass spectrometric characteristics of pyrrolidides of homologous cyclopropane fatty acids are reported and discussed.     

Unprecedented Reductive Esterification of Carboxylic Acids under Hydrogen by Reusable Heterogeneous Platinum Catalysts

Supported metal catalysts have been tested for an unprecedented reductive dimerization of carboxylic acids to esters under 8 bar hydrogen in solvent‐free conditions. Among various metal‐loaded tin oxide catalysts, platinum‐loaded tin dioxide (Pt/SnO₂) shows the highest ester yield for the reaction of dodecanoic acid. Among Pt catalysts on various supports, Lewis acidic oxides, especially SnO₂, show high activity. The most active catalyst, 5 wt% Pt/SnO₂ reduced at 100 °C, is effective for the reductive esterification of various carboxylic acids, and the catalyst is reusable for nine cycles, demonstrating the first successful example for the title reaction. Infrared (IR) studies of a model compound (formic acid) on some metal oxides indicate a strong Lewis acid‐base interaction between SnO₂ and the carbonyl oxygen. For Pt/SnO₂ catalysts with different Pt particle sizes, the activity increases with decreasing size of Pt metal. A cooperative catalysis of the Pt metal nanoparticles and the Sn⁴⁺ Lewis acid sites is proposed.

     

Rhodium‐Catalyzed Decarbonylative Direct Olefination of Arenes with Vinyl Carboxylic Acids

A rhodium(I)‐catalyzed direct C H bond olefination of pyridyl‐substituted arenes with readily available vinyl carboxylic acids has been realized. This reaction occurred efficiently without the need for any external oxidant, affording the ortho‐olefinated products in high yields and excellent regioselectivities. Diversely substituted vinyl carboxylic acids behaved as efficient olefination reagents under the reaction conditions, and a range of functional groups in both coupling partners was well tolerated. Mechanistic studies indicated that a decarbonylation step is involved in this catalytic process, and pivalic anhydride [(t‐BuCO)₂O] acts as the activator of the carboxylic acids for the in situ generation of highly active anhydrides.

     

An Unexpected Potassium Iodide‐Promoted Nucleophilic Substitution Reaction between 2‐Acyloxy‐2H‐azirines and Carboxylic Acids

The acyloxy group of 2‐acyloxy‐2H‐azirines has been displaced by carboxylic acids to generate the corresponding 2‐acyloxy‐2H‐azirines by using potassium iodide as a promotor. This metal‐free method can be performed with a wide scope of substrates readily generating products in moderate to high yields. It also represents an example of nucleophilic substitution between esters and carboxylic acids under metal‐free reaction conditions for the first time.

     

Irreversible Catalytic Ester Hydrolysis of Allyl Esters to Give Acids and Aldehydes by Homogeneous Ruthenium and Ruthenium/Palladium Dual Catalyst Systems

An irreversible hydrolysis reaction of allyl esters ( 1 ) into carboxylic acids ( 2 ) and propanal ( 3 ) was achieved with a ruthenium/palladium (Ru/Pd) dual catalyst system. The optimized catalysts consists of a 1:1:1 mixture of (cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate {[RuCp(MeCN)₃] PF₆}, bis(acetonitrile)palladium dichloride [PdCl₂(MeCN)₂] and 1,6‐bis(diphenylphosphanyl)hexane (DPPHex). The reaction proceeds via isomerization of allyl esters to 1‐propenyl esters and hydrolysis of them to give 2 and 3 . The first isomerization step was virtually catalyzed by the Ru components and the second hydrolysis step was mainly catalyzed by the Pd components. The optimized bidentate phosphine (DPPHex) which has long alkylene chain effectively generates two vacant sites on the Ru centers by bridging coordination. When a chelating bidentate phosphine such as DPPE was employed, only one vacant site remained on the Ru center and resulted in a low activity. This chelating Ru complex of DPPE formed even in the presence of 2 equivalents of Ru or additional 1 equivalent of Pd. These differences in coordination behaviour between DPPHex and 1,2‐bis(diphenylphosphanyl)ethane (DPPE) cause the differences of the catalytic activity in the first step. The phosphine coordination to Pd center slightly decreases the activity of second hydrolysis step but which was compensated by the increasing of the stability of Pd. On the whole, the optimized Ru/Pd dual catalyst system exhibited good performances on the irreversible hydrolysis of allyl esters.     

Microbial Synthesis of Medium‐Chain α,ω‐Dicarboxylic Acids and ω‐Aminocarboxylic Acids from Renewable Long‐Chain Fatty Acids

Biotransformation of long‐chain fatty acids into medium‐chain α,ω‐dicarboxylic acids or ω‐aminocarboxylic acids could be achieved with biocatalysts. This study presents the production of α,ω‐dicarboxylic acids (e.g., C₉, C₁₁, C₁₂, C₁₃) and ω‐aminocarboxylic acids (e.g., C₁₁, C₁₂, C₁₃) directly from fatty acids (e.g., oleic acid, ricinoleic acid, lesquerolic acid) using recombinant Escherichia coli‐based biocatalysts. ω‐Hydroxycarboxylic acids, which were produced from oxidative cleavage of fatty acids via enzymatic reactions involving a fatty acid double bond hydratase, an alcohol dehydrogenase, a Baeyer–Villiger monooxygenase and an esterase, were then oxidized to α,ω‐dicarboxylic acids by alcohol dehydrogenase (ADH, AlkJ) from Pseudomonas putida GPo1 or converted into ω‐aminocarboxylic acids by a serial combination of ADH from P. putida GPo1 and an ω‐transaminase of Silicibacter pomeroyi. The double bonds present in the fatty acids such as ricinoleic acid and lesquerolic acid were reduced by E. coli‐native enzymes during the biotransformations. This study demonstrates that the industrially relevant building blocks (C₉ to C₁₃ saturated α,ω‐dicarboxylic acids and ω‐aminocarboxylic acids) can be produced from renewable fatty acids using biocatalysis.

     

Palladium‐Catalyzed Allylic Alkylation of Doubly Deprotonated Carboxylic Acids

Doubly deprotonated carboxylic acids undergo smooth palladium‐catalyzed carbon alkylations with the allylic substrates methyl allyl carbonate and (E)‐methyl (pent‐3‐en‐2‐yl) carbonate to give γ,δ‐unsaturated carboxylic acids. A diastereoselective and enantioselective protocol leads to (2S,3R)‐hexenoic acid in 87% ee.     

Rhodium‐Catalyzed Enantioselective Hydrogenation of (E)‐Enol Acetate Acids

The novel rhodium complex [Rh(S)‐Phanephos(cod)]‐catalyzed hydrogenation of disubstituted (E)‐enol acetate carboxylic acids is reported. The catalytic cycle works under 30 bar of hydrogen under conventional heating giving different 3‐acetoxy‐2,3‐disubstituted carboxylic acids with ee ≥90%. Hydrogenation occurred also under microwave dielectric heating without eroding the enantioselectivity but improving the overall efficiency of the process. With microwaves, hydrogen pressure and reaction time required for complete hydrogenation dropped to 5 bar and 30 min, respectively. The best performance of this catalyst under microwave irradiation was TON 100, TOF 196 h⁻¹ with ee 99% on a 6‐g scale.     

Heterocycles as Nonclassical Bioisosteres of α‐Amino Acids

Bioisosterism of α‐amino acids is often accomplished by replacing the α‐carboxylate with one of the many known carboxylic acid bioisosteres. However, bioisosterism of the whole α‐amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function. In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of α‐amino acids, which include quinoxaline‐2,4(1H)‐dione, quinoxaline‐2,3(1H)‐dione and quinolin‐2(1H)‐one, azagrevellin and azepine‐derived structures. The binding mode of the crystalized bioisosteres were compared with those of the crystalized α‐amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used. The reported bioisosteres share the following essential structural features for mimicking α‐amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the α‐carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the α‐ammonium. The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters. The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.     

Retracted: Palladium‐Catalyzed Decarboxylative Selective Acylation of 4H‐Benzo[d][1,3]oxazin‐4‐one Derivatives with α‐Oxo Carboxylic acids via Preferential Cyclic Imine‐N‐Directed Aryl C−H Activation

The benzoxazine scaffolds are of much interest as they are found in a large array of natural products and pharmaceutical drugs with diverse activities. We have developed a palladium‐catalyzed decarboxylative selective mono‐ and bis‐acylation of 4H‐benzo[d][1,3]oxazin‐4‐one derivatives with α‐oxo carboxylic acids via preferential cyclic imine‐N‐directed C−H activation. 2‐Aryl‐4H‐benzo[d][1,3]oxazin‐4‐one was acylated with a variety of substituted phenylglyoxylic acids to produce the corresponding products. It was observed that electron‐donating groups (CH₃, OCH₃) at any position of the aromatic ring of phenylglyoxylic acid provided good to excellent yields, whereas phenylglyoxylic acids containing electron‐withdrawing groups (COCH₃, CN, NO₂) gave the products in moderate yields. Interestingly when the reaction was performed with silver triflate (AgOTf) in place of silver nitrate (AgNO₃) in the presence of 4 equivalents of glyoxylic acid, the bis‐acylated product was obtained together with a small amount of mono‐acylated product. This is the first report of acylation of 2‐aryl‐4H‐benzo[d][1,3]oxazin‐4‐ones via C−H activation. The notable features of this reaction are acylation with more challenging heteroarene‐oxo carboxylic acids and alkyl oxo carboxylic acids. This new protocol provides an easy and efficient access to a variety of o‐acyl‐4H‐benzo[d][1,3]oxazin‐4‐one derivatives which are of pharmaceutical importance.

     

Enantioselective Ring Opening Reactions of Azabenzonorbornadienes with Carboxylic Acids

The palladium/silver (Pd/Ag) co‐catalytic system was found to be effective for the enantioselective ring opening reactions of the low reactive azabenzonorbornadienes with weak nucleophilic carboxylic acids. Both aryl and alkyl carboxylic acids are suitable nucleophiles and afforded the cis ring opening products in good yields with excellent enantioselectivities. The absolute configuration of one of the products has been confirmed by X‐ray crystal structure analysis, and a plausible reaction pathway is proposed.

     

Iron‐Catalyzed Oxidative Cleavage of Olefins and Alkynes to Carboxylic Acids with Aqueous tert‐Butyl Hydroperoxide

A new method for the oxidation of aromatic olefins and alkynes has been developed using inexpensive iron(III) chloride hexahydrate (FeCl₃⋅6 H₂O, 5 mol%) catalyst in combination with commercially available aqueous 70% tert‐butyl hydroperoxide (TBHP) as oxidant. The present system works well for aromatic alkenes and alkynes with both electron‐donating and electron‐withdrawing substituents being tolerated. The protocol is free from chromatographic purification and the carboxylic acids are obtained in high yields by simple filtration.     

Versatic Functional Tert-Carboxylic Acids as Metal Extractive Agents

Versatic α-branched tert-carboxylic acids containing C(O)NHNH₂, C(O)NHNHC(O), and C(O)NHN(CH₃)₂ hydrazide groups instead of carboxylic group are synthesized, with subsequent investigation in their physico-chemical, complexing, and extractive properties. While retaining valuable properties inherent to Versatic acids (chemical stability, good compatibility with solvents), functional reagents become selective reagents fit to resolve tasks of current importance in hydrometallurgy.     

Palladium‐Catalyzed Reduction of Carboxylic Acids to Aldehydes with Hydrosilanes in the Presence of Pivalic Anhydride

A palladium catalyst system that allows the reduction of carboxylic acids to the corresponding aldehydes with hydrosilanes as reducing agent and pivalic anhydride as an indispensable reagent has been developed. A simple mixture of commercially available bis(dibenzylideneacetone)palladium(0) [Pd(dba)₂], tri(para‐tolyl)phosphane and methylphenylsilane realized the reduction of various aliphatic carboxylic acids as well as benzoic acids to aldehydes in good to high yields.

     

Chemical Synthesis of Rare Natural Bile Acids: 11α‐Hydroxy Derivatives of Lithocholic and Chenodeoxycholic Acids

A method for the preparation of 11α‐hydroxy derivatives of lithocholic and chenodeoxycholic acids, recently discovered to be natural bile acids, is described. The principal reactions involved were (1) elimination of the 12α‐mesyloxy group of the methyl esters of 3α‐acetate‐12α‐mesylate and 3α,7α‐diacetate‐12α‐mesylate derivatives of deoxycholic acid and cholic acid with potassium acetate/hexamethylphosphoramide; (2) simultaneous reduction/hydrolysis of the resulting △¹¹‐3α‐acetoxy and △¹¹‐3α,7α‐diacetoxy methyl esters with lithium aluminum hydride; (3) stereoselective 11α‐hydroxylation of the △¹¹‐3α,24‐diol and △¹¹‐3α,7α,24‐triol intermediates with B₂H₆/tetrahydrofuran (THF); and (4) selective oxidation at C‐24 of the resulting 3α,11α,24‐triol and 3α,7α,11α,24‐tetrol to the corresponding C‐24 carboxylic acids with NaClO₂ catalyzed by 2,2,6,6‐tetramethylpiperidine 1‐oxyl free radical (TEMPO) and NaClO. In summary, 3α,11α‐dihydroxy‐5β‐cholan‐24‐oic acid and 3α,7α,11α‐trihydroxy‐5β‐cholan‐24‐oic acid have been synthesized and their nuclear magnetic resonance (NMR) spectra characterized. These compounds are now available as reference standards to be used in biliary bile acid analysis.