Work

Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents

Year: 2015

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5b02277

Authors: Masayoshi Jin, Laksmikanta Adak, Masaharu Nakamura

Institutions: Kyoto University, Daiichi-Sankyo (Japan), Kyoto University Institute for Chemical Research

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Ministry of Education, Culture, Sports, Science and Technology, Japan Society for the Promotion of Science, Core Research for Evolutional Science and Technology

Awards: G2504680648, Iron-Catalyzed Enantioselective Cross-Coupling Reaction