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Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

Ling Zhao, Yicong Luo, Junzhe Xiao, Xiaohong Huo, Shengming Ma, Wanbin Zhang

2023Angewandte Chemie International Edition67 citationsDOI

Abstract

Abstract The stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η 3 ‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp 2 −Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

Topics & Concepts

ChemistryCatalysisAlleneSteric effectsBimetallic stripPalladiumArylAlkylationReactivity (psychology)Axial chiralityAldimineStereochemistryCombinatorial chemistryEnantioselective synthesisMedicinal chemistryOrganic chemistryAlternative medicineMedicineAlkylPathologyCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisAsymmetric Synthesis and Catalysis