An Examination of the Palladium/Mor‐DalPhos Catalyst System in the Context of Selective Ammonia Monoarylation at Room Temperature

Abstract

An examination of the [{Pd(cinnamyl)Cl}(2)]/Mor-DalPhos (Mor-DalPhos = di(1-adamantyl)-2-morpholinophenylphosphine) catalyst system in Buchwald-Hartwig aminations employing ammonia was conducted to better understand the catalyst formation process and to guide the development of precatalysts for otherwise challenging room-temperature ammonia monoarylations. The combination of [{Pd(cinnamyl)Cl}(2)] and Mor-DalPhos afforded [(κ(2)-P,N-Mor-DalPhos)Pd(η(1)-cinnamyl)Cl] (2), which, in the presence of a base and chlorobenzene, generated [(κ(2)-P,N-Mor-DalPhos)Pd(Ph)Cl] (1 a). Halide abstraction from 1 a afforded [(κ(3)-P,N,O-Mor-DalPhos)Pd(Ph)]OTf (5), bringing to light a potential stabilizing interaction that is offered by Mor-DalPhos. An examination of [(κ(2)-P,N-Mor-DalPhos)Pd(aryl)Cl] (1 b-f) and related precatalysts for the coupling of ammonia and chlorobenzene at room temperature established the suitability of 1 a in such challenging applications. The scope of reactivity for the use of 1 a (5 mol %) encompassed a range of (hetero)aryl (pseudo)halides (X = Cl, Br, I, OTs) with diverse substituents (alkyl, aryl, ether, thioether, ketone, amine, fluoro, trifluoromethyl, and nitrile), including chemoselective arylations.

Utilizing Mor‐DalPhos/Palladium‐Catalyzed Monoarylation in the Multicomponent One‐Pot Synthesis of Indoles

“…[32] Moreover we sought to exploit, for the first time within a multicomponent reaction sequence of this type, the unusual ability of Mor-DalPhos/Pd catalyst mixtures to promote the selective mono-a-arylation of acetone. [15,33] In a preliminary test reaction (Scheme 2), (Mor-DalPhos)Pd(h 1 -cinnamyl)Cl (A [20] )/Mor-DalPhos mixtures proved useful in catalyzing the chemoselective monoarylation of octylamine with 1-chloro-2-iodobenzene, affording N-(2-chlorophenyl)octyl-A C H T U N G T R E N N U N G amine (B) in 96% isolated yield (4 mol% A/2 mol% Mor-DalPhos, toluene, Cs 2 CO 3 , 908C, 6 h unoptimized; see the Supporting Information for full details).…”

“…Toluene was deoxygenated by sparging with dinitrogen followed by passage through an mBraun double column solvent purification system packed with alumina and copper-Q5 reactant and storage over activated 4 molecular sieves. Mor-DalPhos [13] and (Mor-DalPhos)Pd(h 1 -cinnamyl)Cl (A) [20] were prepared according to literature procedures; all other reagents, solvents and materials were used as received from commercial sources. Column chromatography was carried out using neutral alumina (150 mesh; Brockmann-III; activated).…”

Sulfur-containing DalPhos ligand variants: synthesis and application in Buchwald−Hartwig amination

“…In the specific context of BHA chemistry, Mor-DalPhos has proven to be particularly useful in the selective monoarylation of small, nucleophilic reaction partners (e.g. ammonia 14,23 and hydrazine 16 ), as well as in BHA cross-couplings of challenging aryl mesylate electrophiles. 21 Coordination chemistry studies have confirmed the ability of Mor-DalPhos to bind in a κ 2 -P,N fashion to palladium(II) centers.…”

Synthesis of 2-Alkenyl-Tethered Anilines

“…13 The phenols could then be converted into anilines in two simple steps by either a direct installation of the tosylamide or by an amination followed by a tosyl protection (Scheme 7). 14 …”