Copper-catalyzed di- and trifluoromethylation of α,β-unsaturated carboxylic acids: a protocol for vinylic fluoroalkylations

Dual action: the Lewis acid CuF(2) ?2?H(2)O efficiently catalyzes the reaction between electrophilic fluoroalkylating agents and α,β-unsaturated carboxylic acids by dually activating both reactants, thus affording di- and trifluoromethyl alkenes in high yields with excellent E/Z selectivity.     

α-Bromo-β,γ-unsaturated ketenes for the synthesis of α-benzylamino-β,γ-unsaturated acids

The synthesis of α-benzylamino-β,γ-unsaturated acids has been developed starting from α-bromo-α,β-unsaturated chlorides. Via treatment of the acyl chlorides with (R)-pantolactone in the presence of TEA, the in situ formation of the deconjugated ketenes and their direct transformation into chiral esters was performed. The substitution of bromine with benzylamine, followed by acid hydrolysis, allowed to us obtain enantiomerically enriched α-benzylamino-β,γ-unsaturated acids.     

C(sp~3)–H bond functionalization of non-cyclic ethers by decarboxylative oxidative coupling with α,β-unsaturated carboxylic acids

A copper-catalyzed decarboxylative oxidative coupling of α,β-unsaturated carboxylic acids with non-cyclic ethers is developed.This method provides a new approach for C(sp~3)–H bond functionalization of non-cyclic ethers. Mechanism study shows the reaction involves a radical process.     

Synthesis of β,γ-unsaturated primary amides from α,β-unsaturated acids and investigation of the mechanism

α,β-Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of triethylamine under mild conditions, to afford in high yield and high regioselectivity the corresponding β,γ-unsaturated tritylamides. Detritylation with TFA generates quantitatively β,γ-unsaturated primary amides. An investigation of this deconjugative isomerization was performed.     

Decarboxylative bromination of α,β-unsaturated carboxylic acids via an anodic oxidation

A novel bromination of α,β-unsaturated carboxylic acids was developed via a decarboxylation by virtue of a direct anodic electro-oxidation.In this method,ammonium bromide was employed as a bromine source and the reaction features transition-metal-free,short time,and no additional supporting electrolyte.     

Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids

An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane–water. The amino moiety must be protonated and located α to a carboxylic acid function in order to undergo initial diazotization and successive hydroxylation, since neither β-amino acids nor acid derivatives such as esters and amides undergo hydroxylations. The method is successfully applied for the synthesis of 18 proteinogenic amino acids.     

Synthesis of functionalized indolizines via copper-catalyzed annulation of 2-alkylazaarenes with α,β-unsaturated carboxylic acids

A novel copper-catalyzed annulation of 2-alkylazaarenes with α,β-unsaturated carboxylic acids has been accomplished. This reaction featuring C-H olefination and decarboxylative amination processes provides a concise access to C-2 arylated indolizines from simple and readily available starting materials.     

Copper-catalyzed β-boration of α,β-unsaturated carbonyl compounds with tetrahydroxydiborane

The copper-catalyzed β-boration of α,β-unsaturated carbonyl compounds with tetrahydroxydiborane has been developed. This diboron reagent allows direct, efficient access to boronic acids and their derivatives. Primary, secondary, and tertiary α,β-unsaturated amides are converted to the corresponding β-trifluoroboratoamides in good to excellent yields. The β-boration of a variety of α,β-unsaturated esters and ketones is also reported.     

A novel method for bromodecarboxylation of α,β-unsaturated carboxylic acids using catalytic sodium nitrite

A first novel synthetic utility of catalytic sodium nitrite in combination with aqueous HBr, for bromo decarboxylation of α,β-unsaturated carboxylic acid is described. α,β-Unsaturated carboxylic acid compounds successfully converted into corresponding bromo compounds. The advantages of this protocol are shorter reaction time and moderate to good yields.     

Palladium-catalyzed arylation of α,β-unsaturated Weinreb amides

Palladium-catalyzed arylation of α,β-unsaturated Weinreb amides has been examined to obtain β-aryl-α,β-unsaturated Weinreb amides. The chelation between the palladium center of an alkylpalladium intermediate and Weinreb amide moiety facilitated both coordination and insertion steps.     

Nickel-catalyzed reductive coupling reaction of monofluoroalkyl triflates with alkyl carboxylic acids toward the synthesis of α-alkyl-α-fluoro-alkylketones

The synthesis methods of α-fluoro-arylketones were well-established through electrophilic/nucleophilic fluorination and transition metal catalyzed cross-coupling. However, due to the site selectivity and substrate restriction, only a few cases have been developed to afford α-alkyl-α-fluoro-alkylketones. Herein, we report a general and efficient method of preparing diverse α-alkyl-α-fluoro-alkylketones via nickel-catalyzed reductive coupling reaction of monofluoroalkyl triflates with low-cost industrial raw material alkyl carboxylic acids. These transformations demonstrate high efficiency, mild conditions, and excellent functional group compatibility. This strategy provides a general and efficient method for the synthesis of α-alkyl-α-fluoro-alkylketones.     

TsNBr2 promoted decarboxylative bromination of α,β-unsaturated carboxylic acids

A rapid process for decarboxylative bromination of α,β-unsaturated carboxylic acids have been developed using N,N-dibromo-p-toluenesulfonamide (TsNBr₂). Treatment of cinnamic acids with TsNBr₂ in presence of potassium carbonate in acetonitrile produces corresponding β-bromostyrenes at room temperature. Exclusive formation of (E)-β-bromostyrenes was observed in a stereoselective manner within a very short period of time (5–15?min). This method was further extended for obtaining 1-bromoalkynes from corresponding propiolic acids. Instantaneous formation of bromoalkynes was observed when the reaction was carried out in presence of DBU as a base in acetonitrile at room temperature. A wide variety of cinnamic acids and propiolic acids could be converted to corresponding β-bromostyrenes and 1-bromoalkynes respectively under mild reaction condition with high to excellent yield.     

The cation exchange resin-promoted coupling of alkynes with aldehydes: one-pot synthesis of α,β-unsaturated ketones

Alkynes undergo smooth coupling with aldehydes in the presence of Amberlyst-15^® at room temperature to produce the corresponding α,β-unsaturated ketones in high yields with E-geometry. The use of an inexpensive, readily available, and recyclable cation exchange resin makes this method quite simple and convenient.     

Iron-catalyzed hydroaminocarbonylation of alkynes: Selective and efficient synthesis of primary α,β-unsaturated amides

α,β-Unsaturated primary amides are important intermediates and building blocks in organic synthesis. Herein, we report a ligand-free iron-catalyzed hydroaminocarbonylation of alkynes using NH₄HCO₃ as the ammonia source, enabling the highly efficient and regioselective synthesis of linear α,β-unsaturated primary amides. Various aromatic and aliphatic alkynes are transformed into the desired linear α,β-unsaturated primary amides in good to excellent yields. Further studies show that using NH₄HCO₃ as the ammonia source is key to obtain good yields and selectivity. The utility of this route is demonstrated with the synthesis of linear α,β-unsaturated amides including vanilloid receptor-1 antagonist TRPV-1.     

Palladium-catalyzed oxidative C-H bond and C═C double bond cleavage: C-3 acylation of indolizines with α,β-unsaturated carboxylic acids

A novel palladium-catalyzed C-3 acylation of indolizines with α,β-unsaturated carboxylic acids via C-H bond and C═C double bond cleavage under oxidative conditions is described. The regioselectivity is assisted by the carboxylic group, and the selection of the oxidant is crucial to the reaction.     

C(sp<Superscript>3</Superscript>)–H bond functionalization of non-cyclic ethers by decarboxylative oxidative coupling with α,β-unsaturated carboxylic acids

A copper-catalyzed decarboxylative oxidative coupling of α,β-unsaturated carboxylic acids with non-cyclic ethers is developed. This method provides a new approach for C(sp³)–H bond functionalization of non-cyclic ethers. Mechanism study shows the reaction involves a radical process.     

Pd/C-Catalyzed coupling and cyclization of β-bromo-α,β-unsaturated carboxylic acids with terminal alkynes leading to alkylidenefuranones

Palladium-catalyzed coupling of β-bromo-α,β-unsaturated carboxylic acids with terminal alkynes and subsequent regioselective 5-exo-dig cyclization produces (Z)-alkylidenefuranones in good yields.