A General Palladium–Phosphine Complex To Explore Aryl Tosylates in the N‐Arylation of Amines: Scope and Limitations

Abstract

The scope and limitations of the monoselective N-arylation of various amines by using aryl and hetaryl tosylates are presented. The air-stable and easily accessible Pd(OAc) /CM-phos {CM-phos=2-[2-(dicyclohexylphosphino)phenyl]-1-methyl-1H-indole}catalyst system was able to deal with a wide range of aryl tosylate substrates as well as amine nucleophiles, including primary and secondary cyclic/acyclic aliphatic amines and anilines. NH-Bearing heterocycles such as indole, carbazole, pyrrole, 10-phenothiazine, and 10-phenoxazine were shown to be feasible coupling partners under this catalytic system. The described reaction conditions tolerate a wide range of functional groups and allow an array of aromatic amines as well as unsymmetrical amine products to be easily accessed from the various phenolic derivatives. Interestingly, this catalyst system even offers the opportunity to perform the reaction in water medium. We also report the intermolecular coupling of optically active α-central chiral amines with aryl tosylates without erosion of the enantiomeric purity.

Recent Progress Concerning the N-Arylation of Indoles

“…In this way, a large group of quinazolines S15-2 were prepared in high isolated yields, although similar nonaflates do not react under the developed reaction conditions [ 71 ]. A similar approach for the synthesis of N -arylindoles S15-3 was reported in 2018 by Kwong, albeit with a significantly narrower scope [ 72 ].…”

Facile Assembly of Carbazolyl-Derived Phosphine Ligands and Their Applications in Palladium-Catalyzed Sterically Hindered Arylation Processes

“…There have been a number of literature procedures, for instance, Pd-catalyzed Buchwald–Hartwig amination and Cu-catalyzed C–N bond formation reactions, that we can follow for arylation of the NH carbazole. Because of the economic aspect, we chose a Cu–diamine-complex-catalyzed protocol (instead of Pd-catalyzed methods). , Substoichiometric amounts of CuI and N , N ′-dimethylethylenediamine (DMEDA) were initially employed to facilitate the reaction between 1,2-dibromobenzene ( 1 ) and carbazole ( 2 ) to generate N -(2-bromophenyl)­carbazole ( 3a ). However, a significant amount of reduction side product 3b was observed (essentially a 3a : 3b ratio of 1:1) when this catalyst system was used.…”

Heck Reaction Boosted Heterocycle Ring-Closing and Ring-Opening Rearrangement: A Strategy for the Synthesis of Indolyl-Type Ligands

“… For example, 3-phosphoindole of IDX899 is the pro-drug of a highly potent anti-HIV reverse transcriptase inhibitor that has been approved by the US Food and Drug Administration. In 2007, Kwong and co-workers reported a new class of indolyl-type phosphine ligands that are synthetically valuable because they readily coordinate with metals to accelerate cross-coupling reactions . Meanwhile, phosphine-modified indole derivatives also have great potential in optoelectronic materials …”