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Challenging nickel-catalysed amine arylations enabled by tailored ancillary ligand design

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ABSTRACT

Palladium-catalysed C(sp2)–N cross-coupling (that is, Buchwald–Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp2)–N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known.

No MeSH data available.


Synthesis of the L1-derived nickel complexes (L1)NiCl2 and C1.Isolated yields are provided; DME, 1,2-dimethoxyethane.
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f4: Synthesis of the L1-derived nickel complexes (L1)NiCl2 and C1.Isolated yields are provided; DME, 1,2-dimethoxyethane.

Mentions: We subsequently sought to circumvent the use of costly and air/temperature-sensitive Ni(COD)2. Notwithstanding the reactivity benefits associated with the use of nitriles as co-ligands/additives272830, and the utility of precious metal/nickel photoredox dual catalysis51, in an effort to facilitate end-user uptake we intentionally targeted operationally simple, air-stable nickel pre-catalysts, without recourse to the aforementioned experimental modifications. We thus turned our attention to the synthesis of (L1)Ni(o-tolyl)Cl (C1), which could be reduced to a requisite (L1)Ni(0) species under the amination conditions employed without the formation of inhibiting by-products3052. Combination of L1 with NiCl2(DME) afforded (L1)NiCl2 in 77% isolated yield, and subsequent treatment with (o-tolyl)MgCl afforded (L1)Ni(o-tolyl)Cl (C1) in 93% isolated yield (Fig. 4). Each complex was obtained as an analytically pure solid, and was characterized by use of spectroscopic and crystallographic techniques (Fig. 5; solution and refinement information are provided in Supplementary Tables 1 and 2). The κ2-P,P-bidentate nature of L1 is evident in the solid-state structures of both complexes, which are best described as exhibiting a distorted square planar geometry at nickel (Σangles at Ni∼360°). The catalytic performance of C1 was found to be identical to that of Ni(COD)2/L1 mixtures in the test reaction featured in Fig. 3, with no loss of performance observed following storage of L1 or C1 in air for an extended period (months). Moreover, the performance of C1 was found to be vastly superior to that of Ni(COD)2/L1 under more challenging reaction conditions (that is, room temperature, lower catalyst loadings), in keeping with catalyst inhibition by COD53.


Challenging nickel-catalysed amine arylations enabled by tailored ancillary ligand design
Synthesis of the L1-derived nickel complexes (L1)NiCl2 and C1.Isolated yields are provided; DME, 1,2-dimethoxyethane.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814586&req=5

f4: Synthesis of the L1-derived nickel complexes (L1)NiCl2 and C1.Isolated yields are provided; DME, 1,2-dimethoxyethane.
Mentions: We subsequently sought to circumvent the use of costly and air/temperature-sensitive Ni(COD)2. Notwithstanding the reactivity benefits associated with the use of nitriles as co-ligands/additives272830, and the utility of precious metal/nickel photoredox dual catalysis51, in an effort to facilitate end-user uptake we intentionally targeted operationally simple, air-stable nickel pre-catalysts, without recourse to the aforementioned experimental modifications. We thus turned our attention to the synthesis of (L1)Ni(o-tolyl)Cl (C1), which could be reduced to a requisite (L1)Ni(0) species under the amination conditions employed without the formation of inhibiting by-products3052. Combination of L1 with NiCl2(DME) afforded (L1)NiCl2 in 77% isolated yield, and subsequent treatment with (o-tolyl)MgCl afforded (L1)Ni(o-tolyl)Cl (C1) in 93% isolated yield (Fig. 4). Each complex was obtained as an analytically pure solid, and was characterized by use of spectroscopic and crystallographic techniques (Fig. 5; solution and refinement information are provided in Supplementary Tables 1 and 2). The κ2-P,P-bidentate nature of L1 is evident in the solid-state structures of both complexes, which are best described as exhibiting a distorted square planar geometry at nickel (Σangles at Ni∼360°). The catalytic performance of C1 was found to be identical to that of Ni(COD)2/L1 mixtures in the test reaction featured in Fig. 3, with no loss of performance observed following storage of L1 or C1 in air for an extended period (months). Moreover, the performance of C1 was found to be vastly superior to that of Ni(COD)2/L1 under more challenging reaction conditions (that is, room temperature, lower catalyst loadings), in keeping with catalyst inhibition by COD53.

View Article: PubMed Central - PubMed

ABSTRACT

Palladium-catalysed C(sp2)–N cross-coupling (that is, Buchwald–Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp2)–N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known.

No MeSH data available.