Ligand-controlled regiodivergence in Pd-catalyzed coupling of azlactones with isoprene

• DOI: 10.1016/j.xcrp.2024.101908
• Publication Date: 2024-04-03T14:48:08Z
• Authors: Wei-Nan Zhang; Yan-Cheng Hu; Yan Liu; Xiao-Yu Wang; Ying-Ying Zhao; Qing-An Chen
• Keywords: Isoprene

Transition-metal-catalyzed allylation of azlactones represents an elegant strategy for the synthesis valuable α-quaternary amino acids. While much progress has been achieved, catalytic prenylation and reverse have less explored. Regiodivergent catalysis, aiming at attaining distinct regioisomers from same starting materials through varying catalyst, is emerging in synthetic chemistry. Herein, we present atom-economical coupling isoprene with palladium catalysis which ligand-controlled regiodivergence achieved. With monophosphine PPhCy2 as ligand, reverse-prenylated are produced, while selectivity switches to when bisphosphine ligand dppe. The relies on tuning coordination environment steric effects. Initial rate kinetic analysis suggests a change rate-determining step induced by optimal ligand. Furthermore, this protocol provides expedient entry point access quaternary-prenylated acids, potential incorporation peptides.