Palladium-catalysed C(sp 2 )-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(sp 2 )-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.
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.
A mixture of tris(dibenzylideneacetone)dipalladium(0) (Pd 2 dba 3 ) and 5-(di-tert-butylphos-is shown to be a robust and efficient catalyst system for the hydroxylation of structurally diverse (hetero)aryl halides under mild conditions and with broad substrate scope. Included in this reactivity survey is the successful synthesis of substituted benzofurans and related heteroatomic derivatives, which are formed via the hydroxylation of 2-haloalkynylarenes. Notably, a significant number of the reactions reported herein proceed at room temperature, and we have demonstrated that it is possible to conduct reactions on the benchtop under air using unpurified solvents with negligible loss in reactivity versus related transformations conducted under inert atmosphere conditions. We also report herein the first crystallographically characterized (Bippyphos)Pd(II) complex, which confirms the ability of this synthetically useful ligand to adopt a bidentate binding motif in a manner similar to Buchwalds biarylphosphine ligand class.
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)NiCl 2 ] precatalysts can be employed successfully in such transformations.
Abstract:The application of a Mor-DalPhos/palladium catalyst system in the one-pot, multicomponent assembly of substituted indoles from ortho-chlorohaloarenes, alkyl ketones (including acetone), and primary amines is reported. The described protocols offer improved substrate scope in all three reaction components, under more mild conditions and without the need for an additional drying agent. Also reported are the first examples of such multicomponent reactions where all reactants are combined at the start of the reaction, without the need for inert atmosphere reaction conditions.
A direct perfluoroalkylation of (hetero)arenes using the air- and moisture-stable complex (dppf)Ni(o-tol)Cl was developed (23 examples) which allows for the synthesis of various fluorinated products and tolerates sensitive functional groups including aldehydes, free amino groups and several heterocycles.
The synthesis and/or
NMR/X-ray characterization of a new series
of (L)AuCl complexes is reported, featuring BippyPhos,
AdJohnPhos, silyl ether based ligands including OTips-DalPhos, and
PAd-DalPhos. These complexes, along with previously reported analogues
featuring cataCXium-A, tBuJohnPhos, and Mor-DalPhos,
were screened as precatalysts using LiB(C6F5)4·2.5Et2O as an activator in the hydrohydrazination
of terminal aryl alkynes with hydrazine hydrate under unprecedentedly
mild conditions (25 °C, 1 mol % Au). The precatalyst (cataCXium-A)AuCl
proved to be particularly effective in such transformations, demonstrating
useful scope.
Nickel-Catalyzed Monoarylation of Ammonia. -Substrates are mainly used as chlorides, but bromides or tosylates are also suitable in the chemoselective transformations which are promoted by the Ni/Josiphos system. Ammonia can be applied as commercially available stock solution or as a gas, whereby the yield is sometimes higher in the latter case. Products (VIIa)-(VIId) are isolated as tosylates. Finally, the air-stable precatalyst PINC is tested in the preparation of thiophene (XV). -(BORZENKO, A.; ROTTA-LORIA, N. L.; MACQUEEN, P. M.; LAVOIE, C. M.; MCDONALD, R.; STRADIOTTO*, M.; Angew. Chem., Int. Ed. 54 (2015) 12, 3773-3777, http://dx.doi.org/10.1002/anie.201410875 ; Dep. Chem., Dalhousie Univ., Halifax, Nova Scotia B3H 4R2, Can.; Eng.) -Lehmann 32-074
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