Nickel‐Catalyzed Monoarylation of Ammonia

Abstract

Structurally diverse (hetero)aryl chloride, bromide, and tosylate electrophiles were employed in the Ni-catalyzed monoarylation of ammonia, including chemoselective transformations. The employed JosiPhos/[Ni(cod)2] catalyst system enables the use of commercially available stock solutions of ammonia, or the use of ammonia gas in these reactions, thereby demonstrating the versatility and potential scalability of the reported protocol. Proof-of-principle experiments established that air-stable [(JosiPhos)NiCl2] precatalysts can be employed successfully in such transformations.

Streamlined Synthesis of Diaminopyridines by Pd‐Catalyzed Ammonia Coupling with Deactivated Amino‐Chloropyridines

“…Buchwald and co‐workers reported the palladium‐catalyzed coupling reaction of 2‐Cl‐6‐MeO‐pyridine and 2‐Cl‐3‐NH 2 ‐6‐Me‐pyridine with 2 mol % catalyst loading at 50 °C . Recently, the groups of Stradiotto and Ma reported the coupling reaction of 2‐Cl‐6‐MeO‐pyridine with a nickel and copper‐based catalytic system, albeit at higher catalyst loadings (10 and 5 mol %, respectively) and temperatures (65 and 110 °C, respectively). To compare our methodology with the state‐of‐the‐art, our reaction conditions were applied to 2‐Cl‐6‐MeO‐pyridine.…”

Ni‐Catalyzed Amination Reactions: An Overview

“…Very recently, two research groups independently achieved the nickel‐catalyzed arylation of ammonia with aryl chlorides. Stradiotto and coworkers employed an in situ generated catalyst from [Ni(cod) 2 ]/JosiPhos (1:1 molar ratio) to couple ammonia (commercially available solutions or gas) with an array of (hetero)aryl chorides, bromides, and tosylates with good to high yields65a (Scheme A). Green and Hartwig65b used a JosiPhos‐Ni(0) precatalyst, stabilized by coordination to a benzonitrile ligand in η 2 ‐fashion, in the arylation of ammonia or ammonium sulfate with different aryl chlorides.…”

“…Stradiotto and coworkers employed an in situ generated catalyst from [Ni(cod) 2 ]/JosiPhos (1:1 molar ratio) to couple ammonia (commercially available solutions or gas) with an array of (hetero)aryl chorides, bromides, and tosylates with good to high yields65a (Scheme A). Green and Hartwig65b used a JosiPhos‐Ni(0) precatalyst, stabilized by coordination to a benzonitrile ligand in η 2 ‐fashion, in the arylation of ammonia or ammonium sulfate with different aryl chlorides. The method was also applied to the monoarylation of methylamine and ethylamine in the form of hydrochlorides, although for the latter, a less sterically hindered JosiPhos ligand was required (Scheme B).…”

Nickel‐Catalyzed N‐Arylation of Primary Amides and Lactams with Activated (Hetero)aryl Electrophiles

“…[20h, 24] Moderate conversion to the target product (2a)w as observedw hen using the bisphosphines L1 and L4 and negligible conversion was achieved with the monophosphines L2 and L3.T he poor performance of L1-L4 reaffirmst he notiont hat re-purposing ancillary ligands that functionw ell with Pd is not au niversal strategy for establishing effective Ni-basedc ross-coupling protocols. [19,25] We then turned our attention to the application of other ancillary ligandst hat have provene ffective in Ni-catalyzed C(sp 2 )ÀNc ross-couplings involving alternative nucleophile classes. Whereas rac-BINAP( L5) [26] and SIPr (L6) [20c, d, f, g] performed poorly,b oth JosiPhos( CyPF-Cy) [25] (L7)a nd PAd-Dal-Phos [19] (L8)a fforded high conversion to 2a.T od ifferentiate the catalytic abilities of L7 and L8,w eexamined the cross-coupling of nicotinamide and 1-chloronapthalene (see the Supporting Information), employing air-stable pre-catalysts (L)Ni(otolyl)Cl( L = L8, C1; [19] L = L7, C2 [27] ), [20h, 28] which out-perform related Ni(COD) 2 /L mixtures in ammonia monoarylation.…”

“…[19,25] We then turned our attention to the application of other ancillary ligandst hat have provene ffective in Ni-catalyzed C(sp 2 )ÀNc ross-couplings involving alternative nucleophile classes. Whereas rac-BINAP( L5) [26] and SIPr (L6) [20c, d, f, g] performed poorly,b oth JosiPhos( CyPF-Cy) [25] (L7)a nd PAd-Dal-Phos [19] (L8)a fforded high conversion to 2a.T od ifferentiate the catalytic abilities of L7 and L8,w eexamined the cross-coupling of nicotinamide and 1-chloronapthalene (see the Supporting Information), employing air-stable pre-catalysts (L)Ni(otolyl)Cl( L = L8, C1; [19] L = L7, C2 [27] ), [20h, 28] which out-perform related Ni(COD) 2 /L mixtures in ammonia monoarylation. Whereas negligible conversion was achieved with C2,h igh conversion to the targetc ross-coupling product 2g was realized by use of C1 (10 mol %N i).I nu sing C1,p roducts 2a and 2g were isolated in 82 and 80 %y ield, respectively ( Figure 3).…”