Enantioselektive Synthese von Arylglycinen durch Pd‐katalysierte Kupplung von Schöllkopf‐Bislactimethern mit Arylchloriden

Abstract

Arylglycines 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.