Site-Selective Cross-Coupling Reactions Research Articles

Total Synthesis of Dragmacidins G and H.

The total synthesis of dragmacidins G and H was achieved for the first time by employing nucleophilic aromatic substitution and site-selective cross-coupling reactions using appropriately functionalized pyrazines as substrates. The evaluation of antibacterial activities of dragmacidin G, dragmacidin H, and synthetic analogues against Staphylococcus aureus and the efflux pump-deficient Salmonella Typhimurium revealed that the presence of a Br group on the indole ring adjacent to the sulfide unit was important for increasing antibacterial activities.

Regioselective Suzuki–Miyaura Reactions of Ethyl 2,6-Dibromo­pyrazolo[1,5-a]pyrimidine-3-carboxylate

AbstractA variety of novel disubstituted pyrazolo[1,5-a]pyrimidine derivatives have been prepared via sequential site-selective cross-coupling reactions of ethyl 2,6-dibromopyrazolo[1,5-a]pyrimidine-3-carboxylate. The regiocontrolled Suzuki–Miyaura reaction proceeded with excellent selectivity in favor of position C6 after careful optimization of the cross-coupling conditions. The monobrominated compounds, obtained on a large scale, were subjected to a second arylation, alkynylation or amination, leading to a new series of ethyl 2,6-disubstituted pyrazolo[1,5-a]pyrimidine-3-carboxylates. These results constitute an efficient regioselective approach for diversification of the chemically and biologically interesting pyrazolo[1,5-a]pyrimidine heterocycle at C2 and C6 positions.

Stepwise synthesis of 2,6-difunctionalized ethyl pyrazolo[1,5-a]pyrimidine-3-carboxylate via site-selective cross-coupling reactions: experimental and computational studies.

A variety of novel disubstituted 2-(alknyl, aryl and arylamine)-6-alkynylpyrazolo[1,5-a]pyrimidine derivatives was prepared via sequential site-selective cross-coupling reactions from 2,6-dibromopyrazolo[1,5-a]pyrimidine 3. The regio-controlled Sonogashira-type coupling of 3 with a wide range of terminal alkynes proceeded smoothly with excellent selectivity in favor of the C6-position through careful adjustment of the coupling conditions, followed by the subsequent introduction of alkynyl, aryl or arylamine groups at the C2-position via the Sonogashira, Suzuki-Miyaura and Buchwald-Hartwig coupling reactions, respectively. These promising results allow for further use and diversification of the chemically and biologically interesting pyrazolo[1,5-a]pyrimidine scaffold. In addition, computational studies were conducted to provide explanations for the origin of regioselectivity.

Ligand-Controlled Site-Selective Cross-Coupling.

Site-selective mono-cross-coupling reactions involving dichloro- or dibromo(hetero)aryl substrates are utilized to prepare substituted monochloro- or monobromo(hetero)arenes, which are used as drug components and synthetic precursors. In these reactions, selectivity toward the preferred reaction site of a dihalo(hetero)arene can vary depending on the ancillary ligand of the transition metal catalyst. This review summarizes the examples of ligand-controlled site-selective cross-coupling reactions, specifically those mediated by Pd complexes.

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

An I for an I: Conditions for the intramolecular carboiodination and the simultaneous convergent intramolecular carboiodination/intermolecular Heck reaction of various diiodoarenes were developed. The ability of the Pd(0)/QPhos catalyst/ligand combination to undergo reversible oxidative addition allows these reactions to proceed well, thus increasing both the appeal and utility of this class of substrates in site-selective cross-coupling reactions.

Synthesis, Resolution, and Absolute Configuration of Chiral 4,4′-Bipyridines

A chiral polyhalogenated 4,4'-bipyridine derivative is described allowing an easy access to a new family of chiral 4,4'-bipyridines by site-selective cross-coupling reactions. The absolute configurations of all the HPLC separated enantiomers were determined by X-ray diffraction and electronic circular dichroism coupled with time-dependent density functional theory calculations.

ChemInform Abstract: New Methodology for the Synthesis of 3‐Substituted Coumarins via Palladium‐Catalyzed Site‐Selective Cross‐Coupling Reactions.

ChemInform Abstract: New Methodology for the Synthesis of 3‐Substituted Coumarins via Palladium‐Catalyzed Site‐Selective Cross‐Coupling Reactions.

New Methodology for the Synthesis of 3-Substituted Coumarins via Palladium-Catalyzed Site-Selective Cross-Coupling Reactions

A particularly useful, easy, and concise synthesis of diversified 3-aryl coumarin was achieved using Heck coupling reactions between coumarin and aryliodides. The introduction of the aryl moiety occurred regioselective at the 3-position of the heteroaromatic ring.

General and Efficient Route for the Synthesis of 3,4-Disubstituted Coumarins via Pd-Catalyzed Site-Selective Cross-Coupling Reactions

Palladium-catalyzed site-selective cross-coupling reactions of 3-bromo-4-trifloxycoumarin or 3-bromo-4-tosyloxycoumarin provide an efficient and facile route for the synthesis of 3,4-disubstituted coumarins, which include 3,4-diarylcoumarins, 3-amino-4-arylcoumarins, and 3-aryl-4-aminocoumarins. The order of reactivity of the (pseudo)halide substituents in the coumarins was found to be 4-OTf > 3-Br > 4-OTs.

Diversity-Oriented Synthesis of Functionalized Quinolin-2(1H)-ones via Pd-Catalyzed Site-Selective Cross-Coupling Reactions

Biologically active 3-amino-4-arylquinolin-2(1H)-ones and 3-alkenyl-4-arylquinolin-2(1H)-ones were synthesized in an efficient and concise manner, utilizing readily available 4-hydroxyquinolin-2(1H)-one as starting material. The key steps, which introduced selectivity and diversity in the synthesis, were the palladium-catalyzed site-selective Suzuki-Miyaura/Buchwald-Hartwig amination and Suzuki-Miyaura/Heck coupling reactions of 3-bromo-4-trifloxy-quinolin-2(1H)-one.