A General Palladium‐Catalyzed Amination of Aryl Halides with Ammonia

Abstract

A new robust palladium/phosphine catalyst system for the selective monoarylation of ammonia with different aryl bromides and chlorides has been developed. The active catalyst is formed in situ from [Pd(OAc)(2)] and air- and moisture-stable phosphines as easy-to-handle pre-catalysts. The productivity of the catalyst system is comparable to that of competitive Pd/phosphine systems; full conversion is achieved with most substrates with 1-2 mol % of Pd source and a fourfold excess of ligand (L).

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

“…Although the high abundance and low cost of ammonia make it an ideal nitrogen source in amine synthesis, the small and highly nucleophilic, deactivating nature of this substrate present considerable challenges with respect to its efficient utilization in metal-catalyzed CÀN coupling reactions. While cross-couplings of ammonia with aryl bromides and iodides have been reported using catalysts based on Pd [35][36][37][38] and Cu, [41][42][43][44] the selective monoarylation of ammonia with aryl chlorides represents a challenging reaction, one that has only started to be addressed very recently by the use of specially designed ancillary ligands. Furthermore, selective monoarylation of ammonia employing deactivated aryl chlorides lacking ortho-substituents represents a particular challenge; transformations of this type are limited to examples by Buchwald and co-workers [36] and a very recent report by Hartwig.…”

“…These reactivity challenges include the selective monoarylation of small primary alkylamines (including methylamine), [19,27] the arylation of poorly nucleophilic [27][28][29] or heteroatom-functionalized anilines, [30][31][32] the coupling of base-sensitive substrates, [33] the arylation of lithium amide, [34,35] and the synthesis of anilines from ammonia. [35][36][37][38] However, the structural complexity that is introduced in order to address these specific reactivity challenges 2 , these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl-and arylamines, cyclic and acyclic secondary amines, NÀH imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol % Pd) with excellent functional group tolerance and chemoselectivity.…”

Selective Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with CO and Ammonia

“…[a] X.-F. Wu [15] and direct aminations with ammonia, [16] gave only 12 and 56 % yields of benzamide in this model aminocarbonylation (Table 1, entries 4 and 5). To our delight, we observed full conversion and an 86 % yield of benzamide in the presence of nBuPA C H T U N G T R E N N U N G (1-Ad) 2 (cataCXium A) as the ligand (Table 1, entry 6).…”

Copper‐Mediated Reductive Amination of Aryl Halides with Trimethylsilyl Azide

“…[1] Although the discovery of palladium-catalyzed cross-coupling methods, independently by Buchwald and Hartwig, for the reaction of aryl halides with a variety of amines made it easy to access secondary and tertiary arylamines, [2] the direct synthesis of primary arylamines from aryl halides was not reported until lithium bis(trimethylsilyl)amide was employed as the ammonia equivalent. [3,4] Subsequently, ammonia and ammonium chloride were effectively applied to the palladium- [5] or copper-catalyzed [6] synthesis of primary arylamine derivatives.…”