Palladium-catalyzed cross-coupling reactions enable organic chemists to form C-C bonds in targeted positions and under mild conditions. Although phosphine ligands have been intensively researched, in the search for even better cross-coupling catalysts attention has recently turned to the use of N-heterocyclic carbene (NHC) ligands, which form a strong bond to the palladium center. PEPPSI (pyridine-enhanced precatalyst preparation, stabilization, and initiation) palladium precatalysts with bulky NHC ligands have established themselves as successful alternatives to palladium phosphine complexes. This Review shows the success of these species in Suzuki-Miyaura, Negishi, and Stille-Migita cross-couplings as well as in amination and sulfination reactions.
Pd-N-heterocyclic carbene (NHC)-catalyzed Buchwald-Hartwig amination protocols mediated by Pd-PEPPSI precatalysts is described. These protocols provide access to a range of hindered and functionalized drug-like aryl amines in high yield with both electron-deficient and electron-rich aryl- and heteroaryl chlorides and bromides. Variations in solvent polarity, base and temperature are tolerated, enhancing the scope and utility of this protocol. A mechanistic rationalization for base strength (pKb) requirements is also provided.
In this contribution, recent advances with the PEPPSI style of Pd−NHC catalysts in aryl aminations and aryl sulfinations are reviewed and summarized from both applications and mechanistic standpoints.
Incredible Bulk: A series of N-heterocyclic carbene catalysts (see picture) were prepared and evaluated in the Suzuki-Miyaura reaction. A variety of sterically encumbered tetra-ortho-substituted biaryl products were formed from unreactive aryl chlorides using the isopentyl-substituted catalyst at temperatures ranging from 65 degrees C to room temperature. The cyclopentyl-substituted catalyst was virtually inactive, demonstrating that "flexible bulk" is essential to promote these transformations.
Variable Größe: Eine Reihe von Katalysatoren mit N‐heterocyclischen Carbenliganden (siehe Beispiel) wurde hergestellt und in der Suzuki‐Miyaura‐Reaktion getestet. Mit einem Isopentyl‐substituierten Katalysator wurden die sterisch befrachteten vierfach ortho‐substituierten Biarylprodukte aus wenig reaktiven Arylchloriden zwischen Raumtemperatur und 65 °C erhalten. Dass der Cyclopentyl‐substituierte Katalysator praktisch nicht aktiv war, zeigt die entscheidende Bedeutung eines „flexiblen Raumbedarfs“ bei diesen Umsetzungen.
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