Asymmetric Synthesis Of Chroman Derivatives By Chiral Secondary Amine Catalysts

Chromans or dihydrocoumarins are a class of molecules widely found in large number of natural products or therapeutic agents with various biological activities.Among these,chiral chromans or dihydrocoumarins play important roles on medicinal chemistry.This dissertation mainly focuses on the asymmetric synthesis of chroman derivatives promoted by organocatalysts.We have demonstrated an effective enantioselective[4+2]cycloaddition of ortho-Quinone methides(o-QMs)with aldehydes with chiral secondary amines as catalysts,affording a series of chiral chroman derivatives with good to excellent enatioseletivities.This thesis consists of three chapters.The first part is introduction.It focused on a brief overview of chroman derivatives and the generation methods or applications of o-QMs in synthetic chemistry.The scecond part of this dissertation described the asymmetric synthesis of chroman derivatives.Attracted by the intriguing biological activities of chiral chroman derivatives(e,g.,anti-inflammatory,antibacterial,antioxidant,etc.),an enantioselective[4+2]annulation of aldehydes and o-QMs catalyzed by a chiral secondary amine was developed to afford chiral 2-hydroxy chroman derivatives with up to 98%ee.The third part of this dissertation focused on the synthesis of(S)-equol.Equol is a metabolite produced in vivo from the soybean isoflavones by the action of gut microflor.It is known to be estrogenic and antioxidant activities.Besides,their potential for use in menopausal hormone replacement therapy and the treatment of breast cancer was suggested.We have developed a general strategy for the synthesis of the 2-hydroxychroman derivatives based on a[4+2]cycloaddition of o-QMs with 2-(4-(benzyloxy)phenyl)acetaldehyde,up to 44%yield and up to 88%ee.Then,we have accomplished the synthesis of(±)-equol in six steps with 4-benzyloxy salicylaldehyde as the starting material.Moreover,(S)-equol was afforded in an overall yield of 11% and 87% ee.