Atroposelective Synthesis Of C-N Axially Chiral Compounds Via Asymmetric 1,6-Addition Of Quinone Imides With Indoles

Axially chiral compounds are ubiquitous in chiral ligands,organocatalysts,biologically active molecules and natural products.The catalytic asymmetric synthesis of axial chiral compounds has been well studied,and considerable advances have been achieved in recent years.The majority of previous work focuses on biaryl atropisomers realized by C-C bond formation.However,the more challenging catalytic atroposelective constructing C-N nonbiaryl atropisomers is still largely unexplored and the chemoselectivity in the bond formation is rarely investigated.In this thesis,a new strategy for chemoselective,highly regioselective and highly enatioselective synthesis of axial compounds has been established via chiral phosphoric acid(CPA)-catalyzed cross coupling reactions between quinone imides and indoles.It undergoes1,6-additon with indole when N-sulfonyl quinone monoimine is served as the elelctrophilic regent,forming 3-amino indole with 74% yield and 93% ee in the model reaction.Similarly,the corresponding axial chiral C-N bond can be also formed in excellent yield(up to 98%)and high enantioselectivity(up to 98% ee)in the same 1,6-addition manner when N-sufonyl quinone diimine is utilized.This reaction showcases a great compatibility with substrates with different electronic properties,and the loading of CPA can low to 0.1 mol%.Mechanistic studies by electron paramagnetic resonance(EPR),radical clock test,radical trap experiment suggest that this reaction may proceed via ionic process rather than a radical addition.This work disclosed the first asymmetric 1,6-nucleophilic addition of quinone imine,delivering a series of novel axial chiral structures and providing a novel “nitrogen source”for constructing C-N axial chirality.