Enantioselective Synthesis of Arylglycines via Pd-Catalyzed Coupling of Sch öllkopf Bis-Lactim Ethers with Aryl Chlorides

Angew Chem Int Ed Engl. 2023 Sep 6:e202309868. doi: 10.1002/anie.202309868. Online ahead of print.ABSTRACTArylglycines are important pharmacophores present in several top-selling drugs. This compound class has now been made accessible from abundant aryl chlorides by a Pd-catalyzed Schöllkopf-type amino acid synthesis. In the presence of the catalyst methylnaphthyl(XPhos)-palladium bromide, the base lithium 2,2,6,6-tetramethylpyrrolidide and the additive ZnCl2, tert-leucine-derived bis-lactim ethers were efficiently arylated at room temperature, reaching yields of 95% and diastereoselectivities of 98:2. Hydrolysis gave the corresponding arylglycines in high enantiomeric excess.PMID:37671802 | DOI:10.1002/anie.202309868

Source: Angewandte Chemie - September 6, 2023 Category: Chemistry Authors: Daniel Sowa Prendes Florian Papp Nagesh Sankaran Nardana Sivendran Frederike Beyer Christian Merten Lukas J Goossen Source Type: research