Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

Abstract Using asymmetric catalysis to simultaneously form carbon–carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib—an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery.

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Pd Catalyzed N1/N4 Arylation of Piperazine for Synthesis of Drugs, Biological and Pharmaceutical Targets: An Overview of Buchwald Hartwig Amination Reaction of Piperazine in Drug Synthesis

Current Organic Synthesis ◽

10.2174/1570179415666171206151603 ◽

2018 ◽

Vol 15 (2) ◽

pp. 208-220 ◽

Cited By ~ 3

Author(s):

Vaibhav Mishra ◽

Tejpal Singh Chundawat

Keyword(s):

Bond Formation ◽

Catalyst Design ◽

Biologically Active ◽

Reaction Conditions ◽

Biological Targets ◽

Amination Reaction ◽

Drug Synthesis ◽

Substituted Piperazine ◽

Approved Drugs ◽

Fda Approved Drugs

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.

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The Merger of CF3SO2Na and Palladium Catalysis to Enable Decarboxylative Cross-Coupling for the Synthesis of Aromatic Ketones under Room Temperature

Organic Chemistry Frontiers ◽

10.1039/d1qo00438g ◽

2021 ◽

Author(s):

Pan Xie ◽

Cheng Xue ◽

Cancan Wang ◽

Dongdong Du ◽

Sanshan Shi

Keyword(s):

Visible Light ◽

Room Temperature ◽

Palladium Catalysis ◽

Cross Coupling ◽

Boronic Acids ◽

Aromatic Ketones ◽

Aryl Ketones ◽

Oxocarboxylic Acids

A CF3SO2Na/Pd(OAc)2 co-catalyzed strategy is developed to produce aryl ketones via visible-light-induced decarboxylative cross-coupling of α-oxocarboxylic acids and aryl boronic acids. This process was perfomed under air at room temperature,...

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Metal-free oxidative cross-coupling enabled practical synthesis of atropisomeric QUINOL and its derivatives

Nature Communications ◽

10.1038/s41467-021-22621-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Peng-Ying Jiang ◽

Kai-Fang Fan ◽

Shaoyu Li ◽

Shao-Hua Xiang ◽

Bin Tan

Keyword(s):

Asymmetric Catalysis ◽

Kinetic Resolution ◽

Academic Research ◽

Coupling Reaction ◽

Cross Coupling ◽

Industrial Applications ◽

Lewis Base ◽

Production Costs ◽

Metal Free ◽

Base Catalysts

AbstractAs an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis.

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The Suzuki-Miyaura Cross-Coupling Reactions of 6-Halopurines with Boronic Acids Leading to 6-Aryl- and 6-Alkenylpurines

Synlett ◽

10.1055/s-1999-2753 ◽

1999 ◽

Vol 1999 (7) ◽

pp. 1145-1147 ◽

Cited By ~ 49

Author(s):

Martina Havelková ◽

Michal Hocek ◽

Michal Česnek ◽

Dalimil Dvořák

Keyword(s):

Cross Coupling ◽

Boronic Acids ◽

Coupling Reactions ◽

Cross Coupling Reactions

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Base-Free Synthesis and Synthetic Application of Novel 3-(organochalcogenyl)prop-2-yn-1-yl Esters: Promising Anticancer Agents

Synthesis ◽

10.1055/a-1477-6470 ◽

2021 ◽

Author(s):

Fabiane Gritzenco ◽

Jean Carlo Kazmierczak ◽

Thiago Anjos ◽

Adriane Sperança ◽

Maura Luise Bruckchem Peixoto ◽

...

Keyword(s):

Anticancer Agents ◽

Cross Coupling ◽

Coupling Reactions ◽

Chalcogen Bond ◽

Cross Coupling Reactions ◽

Air Atmosphere ◽

Carbon Carbon Bonds ◽

Palladium Catalyzed ◽

Synthetic Application

This manuscript portrays the CuI-catalyzed Csp-chalcogen bond formation through cross-coupling reactions of propynyl esters and diorganyl dichalcogenides by using DMSO as solvent, at room temperature, under base-free and open-to-air atmosphere. Generally, the reactions have proceeded very smoothly, being tolerant to range of substituents present in both substrates, affording the novel 3-(organochalcogenyl)prop-2-yn-1-yl esters in moderate to good yields. Noteworthy, the 3-(butylselanyl)prop-2-yn-1-yl benzoate proved to be useful as synthetic precursor in palladium-catalyzed Suzuki and Sonogashira type cross-coupling reactions by replacing the carbon-chalcogen bond by new carbon-carbon bonds. Moreover, the 3-(phenylselanyl)prop-2-yn-1-yl benzoate has shown promising in vitro activity against glioblastoma cancer cells.

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ChemInform Abstract: The Suzuki-Miyaura Cross-Coupling Reactions of 2-, 6-, or 8-Halopurines with Boronic Acids Leading to 2-, 6-, or 8-Aryl- and -Alkenylpurine Derivatives.

ChemInform ◽

10.1002/chin.200201163 ◽

2010 ◽

Vol 33 (1) ◽

pp. no-no

Author(s):

Martina Havelkova ◽

Dalimil Dvorak ◽

Michal Hocek

Keyword(s):

Cross Coupling ◽

Boronic Acids ◽

Coupling Reactions ◽

Cross Coupling Reactions

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Chiral Phosphine-Olefin Bidentate Ligands in Asymmetric Catalysis: Rhodium-Catalyzed Asymmetric 1,4-Addition of Aryl Boronic Acids to Maleimides

Angewandte Chemie ◽

10.1002/ange.200501305 ◽

2005 ◽

Vol 117 (29) ◽

pp. 4687-4690 ◽

Cited By ~ 68

Author(s):

Ryo Shintani ◽

Wei-Liang Duan ◽

Takashi Nagano ◽

Atsushi Okada ◽

Tamio Hayashi

Keyword(s):

Asymmetric Catalysis ◽

Boronic Acids ◽

Bidentate Ligands

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Efficient in situ N-heterocyclic carbene palladium(ii) generated from Pd(OAc)2 catalysts for carbonylative Suzuki coupling reactions of arylboronic acids with 2-bromopyridine under inert conditions leading to unsymmetrical arylpyridine ketones: synthesis, characterization and cytotoxic activities

RSC Advances ◽

10.1039/c8ra08897g ◽

2018 ◽

Vol 8 (70) ◽

pp. 40000-40015 ◽

Cited By ~ 6

Author(s):

Nedra Touj ◽

Abdullah S. Al-Ayed ◽

Mathieu Sauthier ◽

Lamjed Mansour ◽

Abdel Halim Harrath ◽

...

Keyword(s):

Coupling Reaction ◽

Cross Coupling ◽

Suzuki Coupling ◽

Boronic Acids ◽

Cytotoxic Activities ◽

Coupling Reactions ◽

Component System ◽

Arylboronic Acids ◽

Cross Coupling Reaction

The in situ prepared four component system Pd(OAc)2, 1,3-dialkylbenzimidazolium halides 2a–i and 4a–i, K2CO3 under CO atmosphere catalyses carbonylative cross-coupling reaction of 2-bromopyridine with various boronic acids to yield unsymmetrical arylpyridine ketones.

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