Air Stable, Sterically Hindered Ferrocenyl Dialkylphosphines for Palladium-Catalyzed C−C, C−N, and C−O Bond-Forming Cross-Couplings

Abstract

Pentaphenylferrocenyl di-tert-butylphosphine has been prepared in high yield from a two-step synthetic procedure, and the scope of various cross-coupling processes catalyzed by complexes bearing this ligand has been investigated. This ligand creates a remarkably general palladium catalyst for aryl halide amination and for Suzuki coupling. Turnovers of roughly 1000 were observed for aminations with unactivated aryl bromides or chlorides. In addition, complexes of this ligand catalyzed the formation of selected aryl ethers under mild conditions. The reactions encompassed electron-rich and electron-poor aryl bromides and chlorides. In the presence of catalysts containing this ligand, these aryl halides coupled with acyclic or cyclic secondary alkyl- and arylamines, with primary alkyl- and arylamines, and with aryl- and primary alkylboronic acids. These last couplings provide the first general procedure for reaction of terminal alkylboronic acids with aryl halides without toxic or expensive bases. The ligand not only generates highly active palladium catalysts, but it is air stable in solution and in the solid state. Palladium(0) complexes of this ligand are also air stable as a solid and react only slowly with oxygen in solution.

Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure–Activity Relationships

“…As mentioned earlier in this paper, reactions catalyzed by complexes of the hindered Josiphos ligand conducted with weak bases 13,14,56,76,77 occur more slowly than reactions catalyzed by complexes of monodentate ligands conducted with weak bases. Nevertheless, reactions of haloarenes containing electron-withdrawing groups, such as enolizable ketone, carboalkoxy, acyl or nitro groups, occurred fast enough to give the coupled product in high yield when K 3 PO 4 was used as base.…”

“…These factors have limited the use of the coupling of amines to produce less expensive intermediates and commodity building blocks. 6,7 (1) Three general classes of reagents react slowly and require high loading of catalyst, even with most of the most recently developed systems: 8 (1) primary alkylamines, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] which form substantial amounts of product from diarylation in the absence of an ortho substituent on the haloarene reagent or an excess of the primary amines; (2) heteroaryl halides, 11,12,15,17,19,[24][25][26][27][28][29][30][31][32] which are important for medicinal chemistry applications, but have reacted more slowly, with narrower scope, and with higher catalyst loadings than aryl halides; and (3) aryl iodides, which react more slowly and provide lower yields than aryl bromides in couplings with amine nucleophiles, 15,17,[33][34][35][36][37][38][39][40][41][42]…”

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“…82 In recent years, much attention has also been devoted to the synthesis and application of ligands of the family of ferrocenylphosphines in palladium-catalysed Suzuki coupling of aryl halides. [83][84][85][86][87][88] The structures of some of these ligands are shown in Figure 5. Thus, the C 3 -symmetric phosphine (pS,pS,pS)-tris(2-methylferrocenyl)phosphine (41) …”

“…86 Other air-stable ligands of the ferrocenylphosphine family are the aryl-ferrocenyl derivatives 44 carrying the bis(dicyclohexyl)phosphino moiety. 87 These ligands were applied in the palladium-catalysed Suzuki cross-coupling of activated as well as unactivated aryl chlorides, and in the asymmetric coupling of an aryl bromide with an arylboronic acid.…”

Reductive Elimination of Ether from T‐Shaped, Monomeric Arylpalladium Alkoxides

“…Only reductive eliminations of alkyl aryl ethers from complexes generated in situ, reductive elimination of an oxygen heterocycle from a single oxapalladacycle,[2] reductive eliminations from arylpalladium alkoxides containing activating groups on the aryl ring, [3,4] and reductive eliminations of biaryl ethers in low yield from isolated complexes [5,6] are documented. Most importantly, the most active catalysts for the palladium-catalyzed etherification of aryl halides contain sterically hindered monophosphines, [1,[6][7][8][9][10][11][12][13][14][15] and no reductive eliminations from arylpalladium alkoxides containing hindered monophosphines have been described.We report reductive eliminations from isolated and structurally characterized examples of such arylpalladium alkoxides. We show that reductive eliminations occur from the observed species containing one aryl, one alkoxide, and one phosphine ligand.…”