Structure–Activity Relationship Analysis of Pd–PEPPSI Complexes in Cross‐Couplings: A Close Inspection of the Catalytic Cycle and the Precatalyst Activation Model

Abstract

A series of Pd-N-heterocyclic carbene (Pd-NHC) complexes with various NHC, halide and pyridine ligands (PEPPSI (pyridine, enhanced, precatalyst, preparation, stabilisation and initiation) precatalysts) were prepared, and the effects of these ligands on catalyst activation and performance were studied in the Kumada-Tamao-Corriu (KTC), Negishi, and Suzuki-Miyaura cross-coupling reactions. The lowered reactivity of more hindered 2,6-dimethylpyridyl complex 4 in the Negishi and KTC reactions is consistent with slow reductive dimerisation of the organometallic reaction partner during precatalyst activation. Comparative rate studies of complexes 1, 4 and 5 in the KTC and Suzuki-Miyaura reactions verify that 4 activated more slowly than the others. A potential on/off mechanism of pyridine coordination to NHC-Pd(0) is also plausible, in which the more basic pyridine stays bound for longer.

Synthesis of an extremely sterically shielding N-heterocyclic carbene ligand

“…22 Only traces of the desired product were detected by 1 H-NMR spectroscopy and EI-MS spectrometry. However, 4,4'-dimethylbiphenyl (2 %) was isolated by column chromatography, exactly matching the added amount of palladium(II) complex 4.…”

InCl3‐katalysierte Synthese von 1,2‐dimetallierten Verbindungen durch direkte Insertion von Aluminium‐ oder Zinkpulver

“…und 7.5 % InCl 3 und lieferte ein Ester-substituiertes 1,2-Dizinkreagens 5 m (50 8C, 2 h) in 75 % Ausbeute [20] in DMPU. Kreuzkupplung mit 4-Brombenzaldehyd (6 j, 1.4 %, PEPPSI-iPr) [27] führte zu dem hochfunktionalisierten Terphenyl 7 m in 69 % Ausbeute (Schema 4). Selbst ein Methylester (4 n) konnte unter diesen Reaktionsbedingungen (50 8C, 2 h) umgesetzt werden, und das funktionalisierte dimetallierte Reagens lieferte nach Negishi-Kreuzkupplung [34] mit Ethyl-3-brombenzoat (6 a) den Triester 7 n in 61 % Ausbeute (Tabelle 2, Eintrag 1).…”

“…Auch in diesem Fall zeigte ESI-MS, dass mehrere Aluminate gebildet wurden. [25] Das entsprechende 1,2-dimetallierte Reagens 5 a reagierte in Gegenwart von Zn(OAc) 2 mit 3-Bromethylbenzoat (6 a) in einer Pd-katalysierten Kreuzkupplung mit 1.4 % PEPPSI-iPr [27] zum Diester 7 a in 63 % Ausbeute (Schema 2). [28] Ebenfalls lieferten 3,4-Dibromtoluol (4 b) und 3,4-Dibrom-o-xylol (4 c) in 54-61 % Ausbeute die entsprechenden 1,2-dimetallierten Reagentien.…”

An N-heterocyclic carbene-palladium-η3-allyl chloride complex for the Suzuki-Miyaura coupling of aryl halides

“…During the last 20 years, NHC's are becoming complementary ligands to phosphines. Their catalytic activity is strongly related to the steric environment of palladium imposed by the N-substituents in the imidazolidene [8][9][10]. NHCs have been used intensively for carbon-carbon bond formation in cross-coupling reactions [7,11,12], even for alkyl electrophiles [13].…”