Chiral Br?nsted Acid-catalyzed Asymmetric(3+2)annulation Of Para-Quinone Methides With 2-Alkyl-3-Vinylindoles

As an important class of quinone derivatives,para-quinone methides(p-QMs)is a type of critical intermediates in the medicinal chemistry and biological synthesis,whose structure could be found in a variety of natural products and pharmaceutical molecules.In this thesis,based on the preparation of a novel chiral phosphoric acid catalyst,a novel(3+2)annulation reaction of indole-derived para-quinone methides and 2-alkyl-3-vinylindoles has been designed and developed,gaving an efficient construction of a series of optically active cyclopenta[b]indoles.This structural unit widely exists in natural products and drugs.The ralated content of this thesis is divided into the following two parts:The first part: The research progress towards the chemistry of p-QMs under catalysis of Br?nsted acid is reviewed.In addition,the 1,6-conjugate additions and annulations of p-QMs have been described since 2019.The second part: The studies of the synthectic methodologies for the cyclopenta-[b]indoles skeleton are reviewed.Centering on the chemistry of p-QMs,we have designed and developed a(3+2)annulation reaction of indole-derived p-QMs with 2-alkyl-3-vinylindoles under the catalysis of a novel chiral Br?nsted acid,and a series of cyclopenta[b]indoles with three consecutive chiral centers are successfully accessed.The optimal reaction conditions have been investigated by screening various factors including catalysts,solvents,temperature,additives as well as catalyst loading.The present methodology to some extent enriches the chemistry of para-quinone methides in organic synthesis.