Chiral Phosphoric Acid-Catalyzed Annulation Of Indolylanilines And Ketones

Polycyclic indoles are ubiquitous in natural products and biologically active molecules.Owing to the importance of these compounds,some strategies have been developed to construct indole polycyclic skeletons in the past decades.Among these methods,it is facile and effective to use simple and easily available ketones as starting materials for the construction of polycyclic skeletons bearing quaternary stereocenters.Although important advances have been made employing ketones for annulation reactions,these methods are limited to specific substrates.In this dissertation,enantioselective synthesis of indole polycyclic compounds by annulation of indolylaniline derivatives and ketones has been studied using chiral phosphoric acids as catalysts.Firstly,using chiral phosphoric acids as catalysts,enantioselective synthesis of aminals with quaternary stereocenters has been realized through annulation of 2-(1H-indolyl)anilines and fluorinated ketones with up to 99%yield and 97%ee.A series of the fluorinated aromatic,aliphatic ketones,and ethyl trifluoropyruvate were suitable.The chiral α-diamino esters bearing trifluoromethyl could be also synthesized.Secondly,chiral phosphoric acid-catalyzed regio-and enantioselective annulation of 2-(1Hindolyl)anilines and isatins has been developed for the synthesis of indole-derived spiro aminals containing quaternary stereocenters with up to 93%ee.The protocol could be expanded to the annulation of 2-(3,5-dimethyl-1H-pyrrol-2-yl)aniline and isatins with up to 94%ee.Thirdly,chiral phosphoric acid-catalyzed Pictet-Spengler reactions of 2-(1-benzyl-1Hindol-2-yl)anilines and isatins have been realized,giving the spiro-indolin-2-ones bearing a quaternary stereocenter with up to 99%yield and 99%ee.The protocol could be applied to enantioselective synthesis of polycyclic pyrroles.Finally,using chiral phosphoric acids as catalyst,the Pictet-Spengler reactions of 2-(1H-indol-7-yl)anilines and isatins have been realized for enantioselective synthesis of spiro compounds bearing a quaternary stereocenter with up to 99%yield and 93%ee.This reaction could be conducted on gram scale without loss of enantioselectivity and reactivity.Notably,this is the first highly enantioselective C6 Pictet-Spengler reaction of indoles.