Transition metal-catalyzed functionalization of pyrazines

Abstract

Transition metal-catalyzed reactions are generally used for carbon-carbon bond formation on pyrazines and include, but are not limited to, classical palladium-catalyzed reactions like Sonogashira, Heck, Suzuki, and Stille reactions. Also a few examples of carbon-heteroatom bond formation in pyrazines are known. This perspective reviews recent progress in the field of transition metal-catalyzed cross-coupling reactions on pyrazine systems. It deals with the most important C-C- and C-X-bond formation methodologies.

6-Substituted Hexamethylene Amiloride (HMA) Derivatives as Potent and Selective Inhibitors of the Human Urokinase Plasminogen Activator for Use in Cancer

“…Buchwald−Hartwig chemistry was established on a related 6-bromopyrazine scaffold to access 6-aminopyrimidine HMA derivative 41. Given the general reactivity of halopyrazines in transition-metal-catalyzed cross-coupling reactions, 68 it is likely that a great many other substituents could be appended at the 6-position of HMA using this chemistry. Screening of such a library against proteins that reportedly bind to HMA (e.g., P2X 7 , 69 NHE1, 70 HIV-1 Vpu, 71 influenza A M2, 72 GnRHR, 73 GABA-A ρ −1, 74 ASIC1a, 75 and GIRK) 76 could help to identify more potent and selective probes for these targets, and possibly therapeutic leads.…”

Orthogonally Reacting Boron Coupling Reagents: A Novel Multicomponent-Multicatalytic Reaction [(MC)2R] of Dichlorovinylpyrazine

“…Suzuki coupling has become one of the most versatile and flexible methods for the functionalization of pyrazines and thus was chosen to complete the sequence. 10 Inclusion of a Suzuki coupling presented substantial additional challenges. The Suzuki coupling and Rh-catalyzed conjugate addition both employ boronic acid coupling partners.…”

A Domino Fusion of an Organic Ligand Depended on Metal‐Induced and Oxygen Insertion, Unraveled by Crystallography, Mass Spectrometry, and DFT Calculations

“…Substituted pyrazines represent the core structure of a number of important natural products as well as laboratory‐made heterocyclic compounds [9] . Besides their medicinal uses, pyrazine derivatives have found technical applications as dyes, electroluminescent materials, organic semiconductors, and as suitable ligands in coordination chemistry [10–12] . Despite their broad utility, efficient synthetic methods for pyrazines are primarily limited to complex reactants, expensive catalysts, or troublesome separation procedures (Table S1 in the Supporting Information).…”

“…[9] Besides their medicinal uses, pyrazined erivatives have found technical applications as dyes, electroluminescent materials, organic semiconductors, and as suitable ligands in coordination chemistry. [10][11][12] Despite their broad utility,e fficient synthetic methods for pyrazines are primarily limited to complex reactants, expensive catalysts, or troublesome separation procedures (Table S1 in the Supporting Information). Solvothermali ns itu metal-assisted ligand reaction is ac onvenient method to produce oligomeric ligands.…”