Pd-PEPPSI-IPr

Pd-PEPPSI-IPr, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride, is a palladium(II) precatalyst that carries the bulky N-heterocyclic carbene (NHC) IPr. PEPPSI stands for pyridine-enhanced precatalyst preparation, stabilisation and initiation. The complex is air- and moisture-stable and can be weighed and stored in air.

How it is activated. In Suzuki–Miyaura, Negishi and Kumada couplings, the organometallic reagent replaces both chlorides. Reductive elimination and loss of the 3-chloropyridine then leave the active (IPr)palladium(0) species.

Suzuki–Miyaura coupling. It couples arylboronic acids with aryl chlorides and bromides, including hindered partners and drug-like heteroaromatics. It also catalyses the challenging alkyl–alkyl coupling.

Negishi coupling. With organozinc reagents it joins alkyl and aryl partners in all combinations. Chlorides, bromides, iodides, triflates, tosylates and mesylates all react, and it outperformed phosphine-based catalysts.

Kumada–Tamao–Corriu coupling. With Grignard reagents it gives hindered biaryls and drug-like heterocycles, with better yields than highly active phosphine ligands under identical conditions. Boc groups are tolerated, and successive couplings in one operation build polyaryl and polyheteroaryl structures.

Buchwald–Hartwig amination. It couples amines with electron-rich and electron-poor aryl and heteroaryl chlorides and bromides, including hindered partners. Solvent, base and temperature can be varied.

Ketones from amides and esters. It cleaves the C–N bond of activated amides and couples them with arylboronic acids to give ketones, more efficiently than palladium–phosphine catalysts. Phenyl esters react in the same way through the C–O bond.