Mono-N-protected amino acid ligands stabilize dimeric palladium(ii) complexes of importance to C–H functionalization

Abstract

C–H activation, C–H functionalization, cyclopalladation, mono-protected amino acid, dimeric Pd amino acid complexes, MPAA coordination, relay of stereochemistry.

Palladium-Catalyzed Late-Stage Direct Arene Cyanation

“…An unusual ligand combination of readily available quinoxaline and N-acetyl-Lalanine (Ac-Ala-OH) [62][63][64][65][66][67][68] proved uniquely suitable with ferricyanate as cyanide donor to effect direct cyanation of arenes (Table 1, see also Tables S1-S8). Our goal was to provide a sufficiently stable and reactive Pd(II) center for metalation (amino acid ligand), combined with a second ligand that is sufficiently coordinating to prevent catalyst deactivation by cyanide ligation, and at the same time does not inhibit the electrophilicity for metalation (quinoxaline).…”

“…64,81,82 MPAA ligands have been shown to be effective in Pd-catalyzed C-H functionalization. [62][63][64][65][66][67][68] Previous reports have shown that the displacement of acetate in Pd(II) complexes by MPAA is facile. 66,68 Considering the fact that Pd(II) and quinoxaline or Pd(II) and amino acid alone could not effect cyanation, it is plausible to assume that the active Pd catalyst in the cyanation reaction features a bidentate amino acid ligand and a monodentate quinoxaline ligand.…”

“…[62][63][64][65][66][67][68] Previous reports have shown that the displacement of acetate in Pd(II) complexes by MPAA is facile. 66,68 Considering the fact that Pd(II) and quinoxaline or Pd(II) and amino acid alone could not effect cyanation, it is plausible to assume that the active Pd catalyst in the cyanation reaction features a bidentate amino acid ligand and a monodentate quinoxaline ligand. 45 Consistent with this assumption, we have observed Pd(quinoxaline) 2 (Ac-Ile-OH) 2 by in situ mass spectrometry (see also Figure S1).…”

“…We speculate that the N-acetyl group of the amino acid ligand could serve as an internal base to shuttle the hydrogen to an external base for the Pd-mediated C-H cleavage step, thus lowering the barrier of C-H metalation. 45,[62][63][64][65][66][67][68] The N-acetyl group is crucial for the electrophilicity of Pd and the proton affinity, [62][63][64][65][66][67][68] as N-Boc (tert-butyloxycarbonyl)-protected amino acid significantly decreased the yield compared with the N-acetyl-protected amino acid (see also Table S6). During catalysis, after an initiation period, during which the active Pd(II) catalyst may form from Pd carboxylate and ligands, we observed a reaction order of zero, with constant reaction rate until conversions up to 70% (see also Figures S2-S5).…”

Bi and trinuclear complexes in palladium carboxylate-assisted C–H activation reactions

“…Recently, Musaev, Lewis et al thoroughly examined the effects of mono-N-protected amino acids (MPAA) in the C-H activation of dimethylbenzylamines (DMBA-s) (Scheme 3). 16 The binuclear complexes 9 analogous to 8 containing bridging MPAA instead of acetates were synthesized. Furthermore, it was shown that these dimeric complexes in the presence of iodobenzene dichloride undergo subsequent C-H functionalization to give other chlorinated dimeric palladacycles 10.…”