Asymmetric Phase-Transfer-Catalyzed S_NAr Reaction Of α-Aryl Esters

1,1-diaryl chiral center is widely present in plenty of drugs and bioactive natural products.The enantioselective arylation of benzyl position constitutes a powerful method for constructing such special scaffolds,which has already achieved remarkable progress.However,direct arylation ofα-aryl esters via S_NAr reaction to synthesize chiral 1,1-diaryl units has not been reported.This paper studied the asymmetric aromatic nucleophilic substitution reaction ofα-aryl esters catalyzed by chiral spirocyclic quaternary ammonium salts,which provides a new method for the synthesis of chiral 1,1-diaryl compounds.In this first chapter,we reviewed the research progress of the synthesis methods of chiral1,1-diaryl compounds,including 1,2-addition reactions of aromatic aldehydes and ketones,1,2-addition reactions of aromatic imines,benzyl C-X bond asymmetric arylation,benzyl C-H bond asymmetric arylation,asymmetric allylic arylation,asymmetric bifunctionalization of aryl olefins,asymmetric reduction of diaryl ketones and desymmetrization of diaryl compounds.However,these synthetic methods have some limitations.First of all,most of the reported synthesis methods rely heavily on transition metal catalysis,which may lead to the use of expensive chiral ligands or precious metals and be accompanied by harsh reaction conditions.Secondly,although several metal-free organocatalytic arylation pathways have been developed,they all require the use of highly active carbonyl enol precursors or special arylation reagents,which greatly limits the scope of substrate and synthetic applications.In the second chapter,we studied the Prolococyte ammonium salt catalyzed asymmetric S_NAr reaction ofα-aryl esters.After,screening the chiar catalysts,solvents,temperature and bases,the optimum reaction conditions were determined as follows:10 mol%spiro cyclic quaternary ammonium salt 2h as catalyst,toluene as solvent,potassium tert-butoxide as base at-40℃.Under these conditions,eleven 1,1-diaryl esters with quaternary carbon stereocenters were synthesized.The highest yield was 78%and the enantioselectivity was63%.The reaction is applicable to variousα-aryl esters substituted by electron-donating and electron-withdrawing substituents,but not to lactones and amide substrates.This method extends the substrate of asymmetric S_NAr to the inertα-aryl esters and provides a new path to construct the 1,1-diaryl quaternary carbon stereocenter.