Dearomative Spiroannulation Reactions Of Phenolic Compounds

Spirocyclic frameworks are commonly occurring structural motifs in many bioactive compounds and have been used as the core building blocks for a wide range of pharmic molecules,functional materials and chiral ligands.Thus,exploring and enriching the synthesis method of spirocyclic compounds has been of vital significance,as well as it is a challenging topic in organic synthesis.Dearomatization reactions provides a straightrorward avenue which convert existed simple rings of aromatic compounds into carbocyclic or heterocyclic frameworks,including spiro-ring,bridge-ring or other complicated fused-ring structures.This extraordinary transformations of aromatic compounds have recently witnessed significant development due to their fascinating feature of building quaternary carbon centers and interesting structures,it also plays as an attractive strategy in the total synthesis of natural products.During the past few years,our research group interested in the dearomative spiroannulation of phenol derivatives and successfully developed several elegant protocols in this field.There are 5 chapters in this dissertation.A short introduction of aromatic compounds has been provided in chapter One,followed by the discovery and development of dearomatization reactions in the early years.Chapter Two is mainly focuses on the dearomative spiroannulation reactions of phenol derivatives.We make major investigation of this field on the literatures reported especially for recent decades,and summarize the dearomative spiroannulation research progress in three branches:(a)oxidative dearomatization of phenol derivatives.(b)aromatic electrophilic dearomative spiroannulation.(c)Transition metal-catalyzed dearomative spiroannulation of phenol derivatives.Based on these elegant protocol reported,studies on exploring novel method to access the ubiquitous spirocyclic framework employing phenol dearomatization strategy are carried out.In chapter Three,a Pd0-catalyzed alkyne migratory insertion/2-naphthol dearomatization cascade process has been accomplished to access a variety of spirocyclic compounds bearing all-carbon quaternary stereogenic centers in high yields with excellent chemoselectivities.This efficient process could complete under the microwave irradiation conditions within 15 minutes and the gram-scale experiment also shows great practicality of this method.In chapter Four,we have developed an intermolecular spiroannulation reactions which 1-bromo-2-naphthols and 2-iodobiphenyls proceed efficiently in the presence of Pd catalyst to generate spirocyclic compounds by sequential oxidative addition,C(sp2)-H bond activation,intermolecular biaryl coupling,and phenol dearomatization.Various spiro fluorene molecules bearing ?,?-unsaturated ketone skeleton could be synthesized under the microwave irradiation conditions with moderate to good yields.It's worth noting that the electron rich phenol substrates could be tolerated under the current condition.In chapter Five,we report an novel Mannich type[4+1]dearomative spiroannulation of N-containing biaryl phenols with aqueous formaldehyde for building the attractive spiroindoline derivatives with broad substrate scope.this method is identified as an economical and environmental friendly transformation because only 5 mol%of acid could catalyze this process and the only by product is H2O.Preliminary results with commercially available phosphoric acid catalyst reveal that the asymmetric transformation is feasible but the enantioselectivity is not very well at present.