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

The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic alpha-chloro- and alpha-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 alpha-arylalkanoates were readily converted to the corresponding alpha-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 methanism 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 alpha-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis Of controlling enantioselectivity in an iron-catalyzed organometallic transformation.