title: Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents.
abstract: The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic α-chloro- and α-bromoalkanoates were coupled with aryl Grignard reagents in the presence of catalytic amounts of an iron salt and a chiral bisphosphine ligand, giving the products in high yields with acceptable and synthetically useful enantioselectivities (er up to 91:9). The produced α-arylalkanoates were readily converted to the corresponding α-arylalkanoic acids with high optical enrichment (er up to >99:1) via simple deprotections/recrystallizations. The results of radical probe experiments are consistent with a mechanism that involves the formation of an alkyl radical intermediate, which undergoes subsequent enantioconvergent arylation in an intermolecular manner. The developed asymmetric coupling offers not only facile and practical access to various chiral α-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis of controlling enantioselectivity in an iron-catalyzed organometallic transformation.
authors.affiliation: †Process Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan.|‡International Research Center for Elements Science, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.|§Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Jin
authors.affiliation: ‡International Research Center for Elements Science, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.|§Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Laksmikanta
authors.initials: L
authors.lastname: Adak
authors.affiliation: ‡International Research Center for Elements Science, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.|§Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D002384:Catalysis; D004952:Esters / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D004952:Esters; D007202:Indicators and Reagents; D007501:Iron