Synthesis of Chiral N-Heterocyclic Carbene Ligands with Rigid Backbones and Application to the Palladium-Catalyzed Enantioselective Intramolecular α-Arylation of Amides

Abstract

Chiral N-heterocyclic carbene (NHC) ligands having a 2,2'-bisquinoline-based C(2) symmetric skeleton were developed. The ligands exhibited good enantioselectivity in palladium-catalyzed intramolecular α-arylation of amides to give 3,3-disubsituted oxindoles.

Octa‐1,7‐diene‐4,5‐diamine Derivatives: Useful Intermediates for the Stereoselective Synthesis of Nitrogen Heterocycles and Ligands for Asymmetric Catalysis

“…Optically pure N , N′ ‐diaryl‐2,7‐dimethylocta‐1,7‐diene‐4,5‐diamines 34 were synthesized starting from bisimine 31 (Scheme ) by the addition of methallylmagnesium chloride in tetrahydrofuran (THF) solution, so obtaining the racemic syn ‐diamine 32 in high yield. Removal of the N ‐substituents with triethylsilane and trifluoroacetic acid, followed by a resolution process using tartaric acid afforded the optically pure primary diamines, e.g., ( S , S )‐ 33 .…”

α‐Arylation Processes

“…In 2011, Murakami and coworkers [82] reported that chiral NHC ligands having a 2,2 ′bisquinoline-based C 2 symmetric skeleton were efficient ligands in the palladium-catalyzed intramolecular α-arylation of amides to afford 3,3-disubstituted oxindoles with good yield and enantioselectivity (Scheme 8.44). The two fused rings attached to the NHC core played an important role in the reaction mechanism.…”

“…In a Schlenk flask is added TMEDA⋅PdMe 2 (0.01 mmol), 2,2 ′ -bisquinoline-based C 2 symmetric NHC ligand (Scheme 8.44) (0.01 mmol), NaOtBu (0.3 mmol), N-(2-bromophenyl)-N-methyl-2-phenylpropanamide (0.2 mmol), and hexane (2 ml) [82]. The Schlenk flask is heated at 50 ∘ C for 20 h. The reaction mixture is cooled to room temperature and the solvent evaporated under reduced pressure.…”

Transition‐Metal‐Mediated Routes to 3,3‐Disubstituted Oxindoles through Anilide Cyclisation

“…[84] In contrast, the (-)-menthone-derived oxazoline NHC-ligand 103i, designed by the Glorius group, afforded product both in excellent yield (99 %) and with excellent selectivity (96 % ee, Table 4, Entry x). [85] The NHC ligand 103j, [86] as well as the well defined Pd complex 103k (R 1 = R 2 = iPr), [87] were also extremely efficient in terms both of yield and of enantioselectivity (Table 4, Entries xi and xii). The Pd complex 103k was also useful for preparing 3-allyl-3-aryloxindoles (Table 4, Entry xiii), [88] and although the development of asymmetric routes to 3,3-disubstituted oxindoles focuses heavily on the use of 3-aryl-substituted compounds, it should be noted that use of the Pd complex 103k resulted in a 70 % ee of a 3-allyl-3-methyl-substituted oxindole (Table 4, Entry xiv).…”