title: Palladium-catalyzed asymmetric benzylation of azlactones.
abstract: Asymmetric benzylation of prochiral azlactone nucleophiles enables the catalytic introduction of a benzyl group towards the synthesis of α,α-disubstituted amino acids. Herein, we report an enantioselective palladium-catalyzed process using chiral bis(diphenylphosphinobenzoyl)diamine (dppba) ligands. Naphthalene- and heterocycle-based methyl carbonates react with a number of azlactones derived from both natural and unnatural amino acids. Monocyclic benzylic electrophiles, for which the barrier to ionization is higher, must employ a phosphate leaving group in order to react. Reaction conditions for electron-rich and -neutral benzylic electrophiles have been developed, and the scope of the reaction has been explored with respect to both reaction partners. The high levels of asymmetric induction, as well as the reactivity pattern of the electrophiles, suggest an η(3)-benzyl intermediate that arises through two distinct pathways.
authors.affiliation: Department of Chemistry, Stanford University, 337 Campus Drive Stanford, CA 94305 (USA). bmtrost@stanford.edu.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Trost
authors.forename: Lara C
authors.initials: LC
authors.lastname: Czabaniuk
keywords: amino acids; asymmetric catalysis; azlactones; benzylation; palladium