Construction Of Atropisomeric Biaryl Compounds Based On Ring-opening Strategy

Atropisomers are stereoisomers arising because of hindered rotation about a single bond,where energy differences due to steric strain or other contributors create a barrier to rotation that is high enough to allow for isolation of individual conformers.Atropisomeric compounds are abundant in natural products,such as vancomycin and gossypol.Due to their distinctive stereocharacters,atropisomeric compounds have become highly desirable as a backbone for chiral ligands and catalysts in asymmetric synthesis,exemplified by BINAP,BINOL,and other related compounds.My doctoral research focused on the asymmetric ring-opening reaction of five-membered cyclic diaryl iodonium salt and six-membered α-hydroxy or carbonyl oxime ester,aiming to construct axially chiral compounds.The thesis consists of the following four parts:Chapter one:A comprehensive survey was conducted to summarize the contemporary methodologies employed for constructing chiral compounds through ring-opening reactions.The diverse array of ring-opening and bond-breaking mechanisms were classified into categories such as C-C,C-N,C-O,C-Si,C-S bonds.For ternary and quaternary rings with high ring strain,the most effective methods involve nucleophilic substitution,cycloaddition,oxidative addition β-carbon elimination and other approaches to release ring tension and facilitate ring opening.Conversely,for five-membered and six-membered rings with low tension,ring-opening was typically accomplished through the breaking of carbon-heteroatom bond using hydrolysis,reduction,and other methods.Chapter two:Enantioselective ring-opening reaction of five-membered cyclic diaryl iodoniums with sterically hindered aromatic amines,catalyzed by copper and chiral anions.To overcome the steric hindrance around the copper center,a novel approach involving cobalt chiral anions was employed,replacing the conventional copper/oxazoline catalytic system.This modification successfully facilitated the participation of sterically hindered aromatic amines in the ring-opening coupling reaction with cyclic iodonium salt,resulting in a remarkably efficient process with exceptional enantioselectivities.Furthermore,the resulting products demonstrated the potential for synthesizing axially chiral N,P-ligands.Mechanistic investigations have been performed,and the crystal structure of chiral anion and iodonium was obtained.Chapter three:Cinchonidine ammonium salt catalyzed the asymmetric ringopening reaction of dibenzo α-carbonyloxime ester with aromatic amine.Axially chiral cyano compounds can be converted to a variety of functionalized axially chiral compounds.To improve the reactivity of the reactants and reduce reaction time,two methyl groups were introduced to the ortho position of the diaryl axis,which effectively increased the torsional strain and enhanced reactivity.Chapter four:A point-to-axis transfer from chiral α-hydroxy ketones to axially chiral cyano compounds via β-carbon elimination.Chiral α-hydroxyketones were converted to α-hydroxoxime esters as key intermediate,which in situ underwent ringopening in basic condition to deliver axially chiral nitriles.This point-to-axial chirality transfer reaction proceeded under mild reaction conditions and yielded various optically active atropisomic nitriles.The resulting cyano compounds could be further advanced to a variety of compounds,including aldehyde,urea and other axially chiral compounds.