Pd-catalyzed Decarboxylative Coupling Research Articles

Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues.

Plant polyphenols, such as the African potato (Hypoxis hemerocallidea)-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol.

Pd-Catalyzed three-component decarboxylative coupling reactions between alkylidene pyrazolones, allyl carbonates and active methylene compounds.

Under the catalysis of Pd2(dba)3·CHCl3/(±)-L5 in THF at room temperature, the three-component decarboxylative coupling reactions among alkylidene pyrazolones, allyl carbonates and active methylene compounds proceeded readily and furnished the desired products in acceptable chemical yields. The chemical architecture of the obtained products was unambiguously confirmed by single crystal X-ray analysis.

Selective Mono- and Dialkynylation of 1-Fluoro-2,2-diiodovinylarenes Using Pd-Catalyzed Decarboxylative Coupling Reactions.

Palladium-catalyzed decarboxylative coupling reactions using alkynoic acids and 1-fluoro-2,2-diiodovinylarenes provide mono- and dialkynylfluoroalkenes with high selectivity. When the reaction was conducted using DBU/DMSO, the hydrodeiodinated monoalkynylfluoroalkene product was formed, whereas performing the reaction using Et3N/THF gave the dialkynylfluoroalkene product. Both reaction conditions gave high yields of the desired enyne and endiyne products bearing fluorine atoms.

Synthesis of Methyl-Protected (±)-Chlorizidine A.

The first total synthesis of the methyl-protected (±)-chlorizidine A has been achieved in 10 steps. Pd-catalyzed decarboxylative coupling and late-stage oxidation were utilized to construct the 5H-pyrrolo[2,1-a]isoindol-5-one scaffold. Samarium(II) iodide mediated Reformatsky reaction and intramolecular Mitsunobu reactions were efficiently applied for the synthesis of the 2,3-dihydropyrrolizine ring system. Chlorizidine A is highly prone to degradation; hence, methyl-protected (±)-chlorizidine A was prepared.

ChemInform Abstract: Synthesis of Biheterocycles Based on Quinolinone, Chromone, and Coumarin Scaffolds by Palladium‐Catalyzed Decarboxylative Couplings.

An efficient Pd-catalyzed decarboxylative coupling of heterocyclic carboxylic acids with heterocyclic halides to achieve the synthesis of biheterocycles of biological interest has been reported. In all cases, the cross-coupling reactions take place rapidly in DMSO in good yields and efficiently proceed in the presence of a PdBr2/DPEphos catalytic system, furnishing the novel biheterocycles based on quinolin-4-one, quinolin-2-one, chromone, and coumarin scaffolds.

ChemInform Abstract: An Unprecedented Pd‐Catalyzed Decarboxylative Coupling Reaction of Aromatic Carboxylic Acids in Aqueous Medium under Air: Synthesis of 3‐Aryl‐imidazo[1,2‐a]pyridines from Aryl Chlorides.

An efficient and practical protocol for palladium-catalyzed decarboxylative arylation of imidazo[1,2-a]pyridine-3-carboxylic acids with aryl chlorides has been developed. Note that the reaction could proceed smoothly without an additive in aqueous medium under an ambient atmosphere, and the addition of H2O could effectively promote the decarboxylative arylation. Particularly noteworthy is that these results represent the first examples of Pd-catalyzed decarboxylative coupling reactions of (hetero) aromatic carboxylic acids in aqueous medium under air, and the first successful examples of the synthesis of 3-aryl-imidazo[1,2-a]pyridines using cheap, diverse aryl chlorides and heteroaryl chlorides as the starting materials.

An efficient route to regioselective functionalization of benzo[b]thiophenes via palladium-catalyzed decarboxylative Heck coupling reactions: insights from experiment and computation.

Pd-catalyzed decarboxylative Heck-type coupling of 3-chlorobenzo[b]thiophene-2-carboxylic acids with styrenes have been developed as an efficient strategy for the construction of functionalized benzo[b]thiophenes. Theoretical analysis shows that AgCl generated during the reaction, instead of Pd, π-coordinates with the carboxyl O atom, making easy the rate-determining CO2 dissociation. The divergent reactivities of the Cl-substituted and H-substituted 3-benzo[b]thiophene-2-carboxylic acids are mainly due to the presence of the Cl substituent, which reduces the adjacent π-π interplay, thereby significantly contributing to decarboxylation. Therefore, the presence of both AgCl and the Cl substituent are of key importance in ensuring the occurrence of the reaction under the given conditions.

An unprecedented Pd-catalyzed decarboxylative coupling reaction of aromatic carboxylic acids in aqueous medium under air: synthesis of 3-aryl-imidazo[1,2-a]pyridines from aryl chlorides.

An efficient and practical protocol for palladium-catalyzed decarboxylative arylation of imidazo[1,2-a]pyridine-3-carboxylic acids with aryl chlorides has been developed. Note that the reaction could proceed smoothly without an additive in aqueous medium under an ambient atmosphere, and the addition of H2O could effectively promote the decarboxylative arylation. Particularly noteworthy is that these results represent the first examples of Pd-catalyzed decarboxylative coupling reactions of (hetero) aromatic carboxylic acids in aqueous medium under air, and the first successful examples of the synthesis of 3-aryl-imidazo[1,2-a]pyridines using cheap, diverse aryl chlorides and heteroaryl chlorides as the starting materials.

Palladium-catalyzed decarboxylative alkoxycarbonylation of potassium aryltrifluoroborates with potassium oxalate monoesters

An efficient method for the preparation of aryl esters has been developed via Pd-catalyzed decarboxylative coupling of potassium aryltrifluoroborates and potassium oxalate monoesters.

Synthesis of Biheterocycles Based on Quinolinone, Chromone, and Coumarin Scaffolds by Palladium-Catalyzed Decarboxylative Couplings.

An efficient Pd-catalyzed decarboxylative coupling of heterocyclic carboxylic acids with heterocyclic halides to achieve the synthesis of biheterocycles of biological interest has been reported. In all cases, the cross-coupling reactions take place rapidly in DMSO in good yields and efficiently proceed in the presence of a PdBr2/DPEphos catalytic system, furnishing the novel biheterocycles based on quinolin-4-one, quinolin-2-one, chromone, and coumarin scaffolds.

Pd-catalyzed decarboxylative coupling of arylalkynyl carboxylic acids with allyl ethers: regioselective synthesis of branched 1,3-enynes

This work reported an efficient and novel method to prepare branched 1,3-enynes via Pd(II)-catalyzed decarboxylative coupling of arylalkynyl carboxylic acids with allylic ethers under mild conditions. Various arylalkynyl carboxylic acids and allylic ethers could participate in the reaction, regioselectively affording the desired branched 1,3-enynes in moderate to good yields.

Pd-catalyzed decarboxylative allylic coupling of acetates of Baylis–Hillman alcohols with propiolic acids: a highly regio- and stereoselective synthesis of 1,5-diarylpent-1-en-4-yne derivatives

Pd-catalyzed decarboxylative allylic coupling of acetates of Baylis–Hillman alcohols with alkynyl carboxylic acids leading to the formation of 1,5-diarylpent-1-en-4-ynes in a highly regio- and stereoselective manner has been developed.

Recent Progress in Pd-Catalyzed Decarboxylative Coupling Reactions of (Hetero)aromatic Carboxylic Acids

羧酸具有无毒、廉价易得、稳定易存储等特点,有关过渡金属Pd催化（杂环）芳基羧酸脱羧的偶联反应在本世纪来得到了迅速发展,大有取代传统偶联反应之势.本文综述了Pd催化（杂环）芳基羧酸脱羧与多种底物的偶联反应,如烯、芳基卤化物、芳烃,三氟芳基硼酸盐等底物,并对相关的反应机理进行了探讨.

ChemInform Abstract: Synthesis of Biaryls via Pd‐Catalyzed Decarboxylative Coupling of Substituted Benzoic Acids with Phenylboronic Acids.

Abstract A Pd-catalyzed decarboxylative coupling of substituted benzoic acids with phenylboronic acid has been developed. Under the optimized conditions, a variety of substituted benzoic acids were found to undergo decarboxylative coupling with various phenylboronic acids to give the desired unsymmetrical biaryls in good yields. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Synthesis of Biaryls via Pd-Catalyzed Decarboxylative Coupling of Substituted Benzoic Acids with Phenylboronic Acids

A Pd-catalyzed decarboxylative coupling of substituted benzoic acids with phenylboronic acid has been developed. Under the optimized conditions, a variety of substituted benzoic acids were found to undergo decarboxylative coupling with various phenylboronic acids to give the desired unsymmetrical biaryls in good yields. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Pd-catalyzed decarboxylative ortho-acylation of O-methyl oximes with phenylglyoxylic acids

Aryl ketones were synthesized via Pd-catalyzed decarboxylative coupling between O-methyl oximes and phenylglyoxylic acids using (NH(4))(2)S(2)O(8) as the oxidant.

Palladium-Catalyzed Decarboxylation of Allenyl 3-Oxoalkanoates: An Efficient Synthesis of 3,4-Allenyl Ketones

An efficient synthesis of 3,4-allenyl ketones via the Pd-catalyzed decarboxylative coupling of the readily available 3-oxoalkanoates is reported. The C-C bond forming reaction occurs under mild conditions producing CO(2) as the only byproduct.

Pd-Catalyzed Dearboxylative Heck Coupling with Dioxygen as the Terminal Oxidant

Pd-catalyzed decarboxylative Heck coupling of aromatic carboxylic acids with various olefins is developed using O(2) as the terminal oxidant. Enhancement of O(2) pressure leads to improving reaction turnover in this transformation and allows significantly reducing catalyst loading for efficient conversion of electron-rich benzoic acids. A Pd catalyst supported by a carbene ligand enables using electron-deficient benzoic acids as coupling partners.

Pd-Catalyzed Decarboxylative Arylation of Thiazole, Benzoxazole, and Polyfluorobenzene with Substituted Benzoic Acids

A Pd-catalyzed decarboxylative coupling of thiazoles and benzoxazole with various substituted benzoic acids is developed. The reaction is compatible with both electron-rich and electron-poor benzoic acids. It can also be extended to the synthesis of polyfluoro-substituted biaryls using polyfluorobenzenes as the starting materials.

Theoretical Analysis of Factors Controlling Pd-Catalyzed Decarboxylative Coupling of Carboxylic Acids with Olefins

Transition-metal-catalyzed decarboxylative coupling presents a new and important direction in synthetic chemistry. Mechanistic studies on decarboxylative coupling not only improve the understanding of the newly discovered transformations, but also may have valuable implications for the development of more effective catalyst systems. In this work, a comprehensive theoretical study was conducted on the mechanism of Myers' Pd-catalyzed decarboxylative Heck reaction. The catalytic cycle was found to comprise four steps: decarboxylation, olefin insertion, beta-hydride elimination, and catalyst regeneration. Decarboxylation was the rate-limiting step, and it proceeded through a dissociative pathway in which Pd(II) mediated the extrusion of CO(2) from an aromatic carboxylic acid to form a Pd(II)-aryl intermediate. Further analysis was conducted on the factors that might control the efficiency of Myers' decarboxylative Heck reaction. These factors included Pd salts, ligands, acid substrates, and metals. (1) Regarding Pd salts, PdCl(2) and PdBr(2) were worse catalysts than Pd(TFA)(2), because the exchange of Cl or Br by a carboxylate from Pd was thermodynamically unfavorable. (2) Regarding ligands, DMSO provided the best compromise between carboxyl exchange and decarboxylation. Phosphines and N-heterocarbenes disfavored decarboxylation because of their electron richness, whereas pyridine ligands disfavored carboxyl exchange. (3) Regarding acid substrates, a good correlation was observed between the energy barrier of R-COOH decarboxylation and the R-H acidity. Substituted benzoic acids showed deviation from the correlation because of the involvement of pi(substituent)-sigma(C(ipso)-Pd) interaction. (4) Regarding metals, Ni and Pt were worse catalysts than Pd because of the less favorable carboxyl exchange and/or DMSO removal steps in Ni and Pt catalysis.