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Synthesis of Axially Chiral Styrenes through Pd‐Catalyzed Asymmetric C−H Olefination Enabled by an Amino Amide Transient Directing Group

Hong Song, Ya Li, Qi‐Jun Yao, Liang Jin, Lei Liu, Yanhua Liu, Bing‐Feng Shi

2020Angewandte Chemie44 citationsDOI

Abstract

Abstract The atroposelective synthesis of axially chiral styrenes remains a formidable challenge due to their relatively lower rotational barriers compared to the biaryl atropoisomers. Herein, we describe the construction of axially chiral styrenes through Pd II ‐catalyzed atroposelective C−H olefination, using a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity (up to 95 % yield and 99 % ee ). Carboxylic acid derivatives of the resulting axially chiral styrenes showed superior enantiocontrol over the biaryl counterparts in Co III ‐catalyzed enantioselective C(sp 3 )−H amidation of thioamide. Mechanistic studies suggest that C−H cleavage is the enantioselectivity‐determining step.

Topics & Concepts

ChemistryThioamideAmideEnantioselective synthesisAxial symmetryCatalysisAxial chiralityYield (engineering)Chiral auxiliaryCombinatorial chemistryStereochemistryOrganic chemistryMaterials scienceMetallurgyEngineeringStructural engineeringAxial and Atropisomeric Chirality SynthesisCatalytic C–H Functionalization MethodsAsymmetric Synthesis and Catalysis