Ferrocenyl Thiolates as Ligands in the Enantioselective Copper-Catalyzed Substitution of Allylic Acetates with Grignard Reagents

Abstract

Abstract:The application of ferrocenyl thiolates as ligands in copper-catalyzed asymmetric substitution reactions of allylic acetates with Grignard reagents is reported. The catalyst formed from lithium thiolate 12 gave the γ-products in high selectivity and with up to 64% ee.Keywords: asymmetric synthesis, copper, ferrocenyl ligands, sulfur, asymmetric catalysis Chiral ferrocenes have received much attention as ligands in transition-metal-catalyzed asymmetric reactions.

The Copper-Catalyzed Asymmetric Allylic Substitution

“…The first successful attempts were made with a chiral leaving group and a stoichiometric organocopper reagent [17][18][19][20][21][22]. It was only in 1995 that a catalytic process was disclosed, by Bäckvall and coworkers [23], with a moderate ee of 42%, later improved to 64% with a new chiral catalyst [24] (Scheme 3). The catalytic system involved a Grignard reagent as primary organometallics, a chiral copper thiolate, and an allylic acetate substituted by an alkyl group.…”

Enantioselective Copper-Catalyzed SN2′ Substitution with Grignard Reagents

“…Van Koten, Bäckvall et al recently reported arenethiolatocopper(I) complexes which acheive ee's of up to 64% in the catalytic S N 2' reaction between allylic acetates and n-BuMgI. [14][15][16] Knochel et al have developed chiral ferrocenyl amine ligands, reporting ee's of up to 98% in the catalytic S N 2' reaction between allylic chlorides and highly hindered diorganozinc reagents. 17,18 Our efforts so far have focused on the enantioselective copper(I)-catalyzed conjugate addition reaction on enones 19 and other Michael acceptors, 20,21 during the course of which we have reported the use of several chiral phosphorus ligands.…”

Copper‐Catalyzed Asymmetric Allylic Alkylation

“…[22] The new ferrocene-thiolatocopper(I) brought added selectivity to the allylic reaction and induced Scheme 11. up to 64 % ee for the addition of n-butylmagnesium iodide to the cyclohexyl allylic acetate (25), as illustrated in Scheme 11. Furthermore, the reaction was carried out in new sets of conditions (in a 3:1 mixture of Et 2 O/toluene at room temperature).…”