Slow Reductive Elimination from Arylpalladium Parent Amido Complexes

Abstract

We report reductive eliminations of primary arylamines from a series of bisphosphine-ligated arylpalladium(II) parent amido complexes that counter several established trends. In contrast to arylamido and alkylamido complexes of the aromatic bisphosphines DPPF and BINAP, parent amido complexes, do not form or undergo reductive elimination of monoarylamines. However, arylpalladium parent amido complexes ligated by the alkylbisphosphine CyPF-t-Bu form in good yield and undergo reductive elimination. Despite the basicity of parent amido ligand and the typically faster reductive elimination from complexes containing more basic amido ligands, the CyPF-t-Bu-ligated arylpalladium parent amido complexes undergo reductive elimination much more slowly than the analogous complexes containing arylamido or alkylamido ligands. Moreover, the parent amido complexes form more rapidly and are more stable thermodynamically in a series of exchange processes than the arylamido complexes. Computational studies support the overriding influence of steric effects on the stability and reactivity of the parent amido complex. The slow rate of reductive elimination causes the arylpalladium amido complex to be the resting state of the coupling of aryl halides with ammonia catalyzed by CyPF-t-Bu-ligated palladium, and this resting state contrasts the Pd(0) or arylpalladium(II) resting states of reactions of aryl halides with amines catalyzed by most palladium complexes.

Palladium-Catalyzed Arylation of Fluoroalkylamines

“…Two prior studies, one on the coupling of benzophenone hydrazone 54 and one on the coupling of ammonia 55 with aryl halides implied that reductive elimination was the turnover-limiting step. However, these studies were conducted with palladium catalysts ligated by the bisphosphines BINAP and Josiphos, respectively.…”

The Buchwald–Hartwig Amination After 25 Years

“…Contrary to the aryl‐ and alkylamido complexes I containing either BINAP or DPPF ligands, the corresponding parent amido complexes neither formed nor underwent reductive elimination with anilines, which is consistent with the fact that these ligands are ineffective in the coupling of aryl halides with ammonia. In contrast, the parent Pd II amido complex 22 , bearing 15 as a ligand, could be generated and slowly underwent reductive elimination at room temperature in the presence of PPh 3 (Scheme ).…”

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

“…κ 2 -P,N) binding modes reversibly as providing a means of facilitating both oxidative addition and reductive elimination steps, for which the electronic demands of the ligand are normally orthogonal; by comparison, while Pd/CyPF-tBu catalysts undergo difficult oxidative additions under mild conditions, the strongly chelating/electron-donating nature of CyPF-tBu discourages reductive elimination, leading to a roadblock in challenging BHA catalytic cycles. 12 Following on our initial explorations of Me-DalPhos (L1) 13 we developed Mor-DalPhos (L2, Figure 1), 5,14-15 which proved to be an extremely effective ligand in challenging Pd 14,[16][17][18][19][20][21] and Au-catalyzed chemistry, 22 allowing for the development of previously unprecedented transformations. 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.…”