Decarboxylative Strategy Research Articles

Access to 2-Arylindoles via Decarboxylative C-C Coupling in Aqueous Medium and to Heteroaryl Carboxylates under Base-Free Conditions using Diaryliodonium Salts.

Easily accessible heteroaromatic carboxylic acids and diaryliodonium salts were successfully employed to construct valuable 2-arylindoles and heteroaryl carboxylates in a regioselective fashion. C2-arylated indoles were produced using a Pd-catalyzed decarboxylative strategy in water without any base, oxidant, or ligand. Heteroaryl carboxylates were prepared under metal and base-free conditions. This protocol was successfully utilized to synthesize Paullone, a cyclin-dependent kinase (CDK) inhibitor.

Decarboxylative thioamidation of arylacetic and cinnamic acids: a new approach to thioamides.

A new decarboxylative strategy has been developed for the synthesis of thioamides via a three-component reaction involving arylacetic or cinnamic acids, amines and elemental sulfur powder, without the need of a transition metal and an external oxidant.

ChemInform Abstract: Facile Synthesis of 4‐Substituted 3,4‐Dihydrocoumarins via an Organocatalytic Double Decarboxylation Process.

AbstractThe first organocatalytic double decarboxylation strategy for an efficient and convenient synthesis of the title compounds is presented.

An expedient synthesis of β-aralkyl cycloalkanones via the sequential conjugate addition of allyl arylacetates and Pd-catalyzed decarboxylative protonation protocol

An expedient protocol for the synthesis of β-aralkyl cycloalkanones was developed via the conjugate addition of allyl arylacetate to cycloalkenones and the following Pd-catalyzed decarboxylative protonation strategy.

Gas-Phase Synthesis of the Homo and Hetero Organocuprate Anions [MeCuMe]-, [EtCuEt]-, and [MeCuR]-

The homocuprates [MeCuMe]- and [EtCuEt]- were generated in the gas phase by double decarboxylation of the copper carboxylate centers [MeCO2CuO2CMe]- and [EtCO2CuO2CEt]-, respectively. The same strategy was explored for generating the heterocuprates [MeCuR]- from [MeCO2CuO2CR]- (R = Et, Pr, iPr, tBu, allyl, benzyl, Ph). The formation of these organocuprates was examined by multistage mass spectrometry experiments, including collision-induced dissociation and ion-molecule reactions, and theoretically by density functional theory. A number of side reactions were observed to be in competition with the second stage of decarboxylation, including loss of the anionic carboxylate ligand and loss of neutral alkene via beta-hydride transfer elimination. Interpretation of decarboxylation of the heterocarboxylates [MeCO2CuO2CR]- was more complex because of the possibility of decarboxylation occurring at either of the two different carboxylate ligands and giving rise to the possible isomers [MeCuO2CR]- or [MeCO2CuR]-. Ion-molecule reactions of the products of initial decarboxylation with allyl iodide resulted in C-C coupling to produce the ionic products [ICuO2CR]- or [MeCO2CuI]-, which provided insights into the relative population of the isomers, and indicated that the site of decarboxylation was dependent on R. For example, [MeCO2CuO2CtBu]- underwent decarboxylation at MeCO2- to give [MeCuO2CtBu]-, while [MeCO2CuO2CCH2Ph]- underwent decarboxylation at PhCH2CO2- to give [MeCO2CuCH2Ph]-. Each of the heterocuprates [MeCuR]- (R = Et, Pr, iPr, allyl, benzyl, Ph) could be generated by the double decarboxylation strategy. However, when R = tBu, intermediate [MeCuO2CtBu]- only underwent loss of tBuCO2-, a consequence of the steric bulk of tBu disfavoring decarboxylation and stabilizing the competing channel of carboxylate anion loss. Detailed DFT calculations were carried out on the potential energy surfaces for the first and second decarboxylation reactions of all homo- and heterocuprates, as well as possible competing reactions. These reveal that in all cases the first decarboxylation reaction is favored over loss of the carboxylate ligand. In contrast, other reactions such as carboxylate ligand loss and beta-hydride transfer become more competitive with the second decarboxylation reaction.

Synthesis of 2,3,4‐Trisubstituted 2,5‐Dihydrofuran Derivatives.

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Synthesis of 2,3,4-Trisubstituted 2,5-Dihydrofuran Derivatives

Recently, synthesis of methylenetetrahydrofurans has received much attention due to their versatile usefulness in organic synthesis. The compounds were prepared most frequently either by the Zn(II)/amine-catalyzed coupling reaction of alkylidenemalonates with propargyl alcohol or Michael addition of propargyl alcohol to alkylidenemalonates followed by a palladium-mediated exo-dig cyclization. Methylenetetrahydrofurans can be used for the synthesis of polysubstituted tetrahydrofurans or furans. However, chemical transformations of these valuable compounds were not reported much. Very recently we reported the synthesis of 2,5-dihydrofuran derivatives by the sequential introduction of propargyl alcohol at the primary position of the Baylis-Hillman adducts, radical cyclization, iodolactonization, and finally decarboxylation strategy (Scheme 1). During the investigations we reasoned that we could prepare 2,4-disubstituted 2,5-dihydrofuran derivative (B) by following the similar protocol from the methylenetetrahydrofuran 3a (Scheme 2). Starting methylenetetrahydrofuran 3a was prepared in 51% yield from the reaction of benzylidenemalonate 1a and propargyl alcohol (2a) in the presence of n-BuLi (1.1 equiv) and CuI (30 mol%) in THF by following the reported method, which described the reaction with propargyl amines instead of propargyl alcohol. With the starting material 3a, we examined the hydrolysis of ester groups. Initially we tried the hydrolysis with LiOH in aq THF at room temperature. From the reaction, we obtained a mixture of starting material 3a and ethyl 2-phenyl-4-methyl-2,5dihydrofuran-3-carboxylate (4a). After many trials we found that the use of excess LiOH (3 equiv) at elevated temperature (50-60 C) gave 5a in good yield (75%) instead

Synthesis of 3,4‐Disubstituted 2,5‐Dihydrofurans Starting from the Baylis—Hillman Adducts via Consecutive Radical Cyclization, Halolactonization, and Decarboxylation Strategy.

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Synthesis of 3,4-disubstituted 2,5-dihydrofurans starting from the Baylis–Hillman adducts via consecutive radical cyclization, halolactonization, and decarboxylation strategy

A facile synthetic method of 3,4-disubstituted 2,5-dihydrofurans and 2,5-dihydropyrroles starting from the Baylis–Hillman adducts was developed. The 2,5-dihydrofuran skeleton was constructed via the consecutive radical cyclization, hydrolysis, halolactonization, and spontaneous decarboxylation strategy starting from the modified Baylis–Hillman adducts.