Effective Chiral Ferrocenyl Phosphine‐Thioether Ligands in Enantioselective Palladium‐Catalyzed Allylic Alkylations

Abstract

Chiral ferrocene-derived phosphine-thioether mixed donor ligands supported by heterocycles effected the palladium-catalyzed enantioselective allylic alkylations with excellent yields and enantioselectivities (up to 96% ee). With cyclic and unsymmetrical allylic acetates as substrate, the corresponding alkylated products with enantioselectivities up to 87% ee were obtained. Based on X-ray crystallographic and NMR studies, the origin of the observed enantioselectivities is discussed.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“… 307 , 308 The related ligand L93 proved to be effective in the enantioselective allylation of indoles, 309 and in the alkylation of 1,3-diphenylallyl acetate and cyclic allylic substrates with a range of malonates ( ee values up to 96% and 87%, respectively; Scheme 83 b). 297 L92 and L93 are two of the many ferrocene-based ligands that were developed since Pregosin’s seminal work in 1996 on the use of ferrocene-based P-thioether ligands 310 in Pd-catalyzed allylic alkylation. 306 Although the problem of substrate and nucleophile scope in Pd-catalyzed allylic alkylation was not fully solved with ligands L92 and L93 , the promising results with substrates and nucleophiles other than 1,3-diphenylallyl acetate and malonate indicated considerable potential for P -thioether ligands.…”

Resolution of the Atropochiral Biminap Ligand and Applications in Asymmetric Catalysis

“…This is illustrated by the second generation Grubbs Ru catalyst for alkene metathesis, where the effect of the highly electron‐rich NHC ligand is balanced by that of a PCy 3 ligand 6. In the chiral chelating version (Scheme ), beyond Achiwa’s early Rh‐bcpm catalysts for asymmetric hydrogenation of ketones (where the electron‐rich dicyclohexylphosphine end is balanced by a PPh 2 end),7 one may cite Takaya’s atropochiral Rh‐binaphos catalyst for asymmetric hydroformylation (where the electron‐poor phosphite end is balanced by a napht‐PPh 2 end),8 and the Chan’s recent Pd‐Imidazolylphosphine‐thioether catalysts for Tsuji–Trost allylation (where the electron‐poor imidazolylphosphine end is balanced by a Fc‐SR end) 9. In the same vein, the atropochiral biminap ligand 1 has been devised as a bimip/binap hybrid, where the electron‐poor imidazolyphosphine end is balanced by a napht‐PPh 2 end 10…”

Synthesis of Novel Ferrocenyl‐Based P,S Ligands (ThioClickFerrophos) and Their Use in Pd‐Catalyzed Asymmetric Allylic Substitutions

“…Accordingly, as shown in Figure 1, a P,S ligand should be preparable either by sulfination of the cyclopentadienyl moiety followed by phosphination of the triazole ring (Type I) or vice versa (Type II). Here we describe the preparation of novel P,S‐ferrocenyl ligands (ThioClickFerrophos) and their applications in Pd‐catalyzed asymmetric allylic substitution reactions 10…”