Modified (NHC)Pd(allyl)Cl (NHC = N-Heterocyclic Carbene) Complexes for Room-Temperature Suzuki−Miyaura and Buchwald−Hartwig Reactions

Abstract

A series of (NHC)Pd(R-allyl)Cl complexes [NHC: IPr = N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, SIPr = N,N'-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene; R = H, Me, gem-Me2, Ph] have been synthesized and fully characterized. When compared to (NHC)Pd(allyl)Cl, substitution at the terminal position of the allyl scaffold favors a more facile activation step. This translates into higher catalytic activity in the Suzuki-Miyaura and Buchwald-Hartwig reactions, allowing for the coupling of unactivated aryl chlorides at room temperature in minutes. In the Suzuki-Miyaura reaction, aryl triflates, bromides, and chlorides react with boronic acids using very low catalyst loading. In the N-aryl amination reaction, a wide range of substrates has been coupled efficiently; primary-, secondary-, alkyl-, or aryl-amines react in high yields with unactivated, neutral, and activated aryl chlorides and bromides. In both reactions, extremely hindered substrates such as tri-ortho-substituted biaryls and tetra-ortho-substituted diarylamines can be produced without loss of activity. Finally, the present catalytic system has proven to be efficient with as low as 10 parts-per-million (ppm) of precatalyst in the Buchwald-Hartwig reaction and 50 ppm in the Suzuki-Miyaura reaction.

Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure–Activity Relationships

“…11 Thus, we also tested reactions of primary amines with 3-chloropyridine using the allylpalladium halide adduct of this ligand (NHC)Pd(R-allyl)Cl, which Nolan recently reported to be highly efficient for some combinations of aryl halides and amines. 31,66 Table 2 provides a comparison of the activity and selectivity of catalysts containing CyPF-tBu 1, the most recently developed biaryl phosphine XPhos 2, and the catalyst containing the SiPr carbene 3 for the reaction of 3-chloropyridine with ocylamine. The data in this table correspond to reactions under the reported optimal conditions for each of the catalyst systems.…”

“…The data in this table correspond to reactions under the reported optimal conditions for each of the catalyst systems. 12,66 Reaction of 3-chloropyridine with 1.2 equiv of octylamine in the presence of 0.005 mol % of Pd(OAc) 2 /CyPF-t-Bu afforded a 92% yield of the N-octyl aminopyridine with no side product from diarylation that could be detected by GC/MS or 1 H NMR spectroscopy. In contrast, the reaction conducted with an order of magnitude more catalyst from X-phos ligand 2 (0.05 mol %) led to less than 40% conversion.…”

“…Nolan reported that the reaction of benzylamine with 2,6-dimethyl-1-bromobenzene at 80 °C using just 0.001 mol % of a carbene-ligated allyl-Pd complex occurred to form 88% yield of coupled product. 66 Reactions of less hindered bromoarenes and of aliphatic amines with palladium-carbene ctalysts are either unreported 66 or require loadings near 1 mol %. 16 Reactions of α-branched primary amines were somewhat slower and required more catalyst than those of linear primary amines, but the required loadings remained lower than those used previously.…”

“…12 Nolan reported one example of the extremely hindered 2,6-di-iso-propylaniline with the hindered chloroarene 2,6-dimethyl-1-chlorobenzene in the presence of 0.01 ml% of catalyst to give 93% isolated yield. 66 Reactions of electron-deficient primary heteroaryl amines also occurred in the presence of the combination of Pd(OAc) 2 and CyPF-t-Bu, but were slower and required higher catalyst loadings than the reactions of electron-rich primary arylamines (Table 6, entries 6, 9-10 and 15-16). 26 Nevertheless, 2-aminopyridine, 2-aminopyrimidine and 2-aminobenzothiazole (Table 6, entries 6, 9, 10, 15 and 16) coupled with chlorobenzene and or bromobenzene to afford the desired products in 62-97% yields in the presence of 0.5-1.0 mol % catalyst.…”

Bis(imino)acenaphthene (BIAN)-supported palladium(ii) carbene complexes as effective C–C coupling catalysts and solvent effects in organic and aqueous media

“…5 Complexes based on group X metals are the most proficient in this task and can be rendered soluble in appropriate organic solvents using a range of spectator ligands such as 3-chloropyridine, triethylamine, and allyl moieties. [6][7][8][9] Suzuki catalysts often employ bulky phosphine ligands that result in optimal catalytic activity and selectivity. However, phosphine ligands are typically susceptible to oxidation and metal-ligand degradation.…”