Plausible PEPPSI catalysts for direct C–H functionalization of five-membered heterocyclic bioactive motifs: synthesis, spectral, X-ray crystallographic characterizations and catalytic activity

Abstract

In this study, a series of benzimidazolium salts were synthesized as asymmetric N-heterocyclic carbene (NHC) precursors.

Palladium-Catalyzed Cross-Coupling Reaction via C–H Activation of Furanyl and Thiofuranyl Substrates

“…In contrast to previous studies by the group of Özdemir involving alkyl substituents (for example, benzhydryl [35], 1,3-dioxalane-2-yl [38], 2-morpholinoethyl [43] or 2morpholinoethyl [33]), instead of the styryl group on the benzimidazolylidene ligand, low conversions in the range of 10 to 21% were observed when 4-bromoanisole (11b) or 4-bromotoluene (11e) was employed. Repeating the runs with the sterically more crowded 2-bromotoluene (11f) did not profoundly alter the reactivity of the catalytic system, and conversions of 7-23% were measured.…”

“…Initially developed by the group of Organ [17], Pd-PEPPSI-NHC complexes (PEPPSI = Pyridine-Enhanced Pre-catalyst Preparation Stabilization and Initiation) [18,19], thanks to their easy decoordination of the ancillary ligand and the formation of the active Pd(0) species [20], have been shown to be particularly efficient in cross-coupling, such as the Suzuki-Miyaura [21][22][23], Mizoroki-Heck [23,24], Kumada-Tamao-Corriu [25], Negishi [26], Sonogashira [23,27], and Buchwald-Hartwig reactions [28,29] or the activation of the C-H bonds of heteroarenes [30][31][32][33].…”

Preparation of von Hippel-Lindau (VHL) E3 ubiquitin ligase ligands exploiting constitutive hydroxyproline for benzylic amine protection

“…KOAc, and either 0.1 mol% or 3 mol% of Pd(OAc) 2 in anhydrous DMA, as previously reported. 11,14 The desired product 9 was obtained in excellent yields in both cases (Table 1, entries 1 and 2); however, both reactions generated two byproducts identied as 4,4 0 -(4-methylthiazole-2,5-diyl) dibenzonitrile (23) as a yellow solid (see page S11, Fig. 1S †) and 4,4 0 -dimethyl-5,5 0 -bithiazole (24) as a bright yellow solid (see page S12, Fig.…”

“…Various palladium pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI™) precatalysts have been demonstrated to afford C-H arylation products, including 9, in high yields. [21][22][23] However, to our knowledge, these precatalysts have not been reported for the preparation of VHL ligands. Treatment of 5 and 6 with Organ's commercial Pd-PEPPSI-IPr 24,25 at varied reaction temperatures and reaction times (Table 1, entries 6-9) furnished 9 in yields comparable or superior to those involving Pd(OAc) 2 with the benet of slightly reduced formation of bis-arylated 23 and no evidence of 24 (Fig.…”