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

Abstract

We describe a systematic study of the scope and relationship between ligand structure and activity for a highly efficient and selective class of catalysts for the amination of heteroaryl and aryl chlorides, bromides and iodides containing sterically hindered chelating alkylphosphines. In the presence of this catalyst, aryl and heteroaryl chlorides, bromides and iodides react with many primary amines in high yields with part-per-million quantities of palladium precursor and ligand. Many reactions of primary amines with both heteroaryl and aryl chlorides, bromides and iodides occur to completion with 0.0005-0.05 mol % catalysts. A comparison of the reactivity of this catalyst for coupling of primary amines at these loadings is made with catalysts generated from hindered monophosphines and carbenes, and these data illustrate the benefits of chelation. Thus, these complexes constitute a fourth-generation catalyst for the amination of aryl halides, whose activity complements catalysts based on monophosphines and carbenes.

A Highly Versatile Catalyst System for the Cross‐Coupling of Aryl Chlorides and Amines

“…[5][6][7] Insights gained regarding the key mechanistic steps in Pd-catalyzed C À N coupling have enabled the development of several highly active classes of catalysts for the cross-coupling of less expensive and more abundant (compared to bromo and iodo compounds), but less reactive, aryl chloride substrates to amines at low catalyst loadings, with excellent yields and reasonable scope. [8] There now exist several ligand classes that promote such difficult C À N coupling reactions of aryl chlorides, including ( Figure 1) bulky trialkylphosphanes, [9][10][11][12] N-heterocyclic carbenes, [13][14][15] biaryldialkylphosphanes [7] and chelating bisphosphanes, [16,17] as well as N-or O-heteroatom-functionalized phosphanes. [18][19][20][21][22][23][24][25][26] More recently, difficulties associated with particularly challenging classes of amine substrates have been addressed by the use of specialized task-specific ligands in combination with a judiciously selected Pd precursor.…”

“…For instance, Hartwig and co-workers have demonstrated that specific ligand variants within the Josiphos family display high activity and scope in the cross-coupling of aryl bromides and chlorides to primary amines; however, secondary amines proved to be rather poor partners. [16,17,35] Sterically demanding N-heterocyclic carbenes represent another well-explored ligand class for C À N coupling reactions, led primarily by the groups of Nolan and Organ. [13][14][15] While secondary amines are readily cross-coupled to aryl chlorides under mild conditions with low Pd loadings, adequate reactivity with smaller, nucleophilic primary amines has not been accomplished.…”

Ferrocenyl‐Aryl Based trans‐Chelating Diphosphine Ligands: Synthesis, Molecular Structure and Application in Enantioselective Hydrogenation

“…Finally, borane decomplexation was accomplished by treatment with either diethylamine [1aA C H T U N G T R E N N U N G (BH 3 ) 2 ] or morpholine [24] [1b-Scheme 1. Synthesis of ligands 1a-1d.…”

Katalytische enantioselektive Olefinmetathese in der Naturstoffsynthese: chirale Metallkomplexe für hohe Enantioselektivitäten und vieles mehr

“…93 %; Schema 14). [37] Für einen verwandten Palladium-katalysierten Prozess mit Ammoniak wird berichtet, dass es mit dem Josiphos-Liganden, einer chiralen Bisphosphanvariante von 55, [38] …”