Triazolium Salt And Isothiourea Catalyzed Asymmetric Synthesis Of Chiral Spirocyclic 1,3-Diketones

Chiral spirocyclic 1,3-diketones with an all-carbon framework are structural units that can be derived to privileged ligands and found in bioactive natural products and pharmaceuticals.In this dissertation,a series of racemic spirocyclic 1,3-diketones were prepared by intramolecular Dieckmann condensation of carboxylic acid compounds mediated by P₂O₅/Tf₂O under mild conditions.Because asymmetric synthetic methods to prepare these chiral compounds is limited.Subsequently,we have developed a 1,2,3-triazolium salt catalyzed enantioselective transannular C-acylation of enol lactones,providing a series of enantioenriched spirocyclic 1,3-diketones in moderate to high yields and enantioselectivities.These unsatisfactory results prompt us to search for a better catalytic system.Finally,an isothiourea catalyzed asymmetric Steglich-type rearrangement of enol lactones was realized for the synthesis of these enantioenriched spirocyclic 1,3-diketones in excellent enantioselectivities.This paper will describe these methodologies in the following three aspects:In chapter 1:A brief introduction of the synthesis of racemic spirocyclic 1,3-diketones was described,and the background of the synthesis of chiral spirocyclic 1,3-diketones was summarized in detail.In chapter 2:We have developed an intramolecular Dieckmann condensation of?-substituted cyclic ketone with a terminal carboxylic acid to synthesize spirocyclic 1,3-diketones mediated by P₂O₅/Tf₂O.This methodology provided access to a range of spirocyclic 1,3-diketones under mild conditions.Subsequently,we introduced the types of reactions catalyzed by 1,2,3-triazolium salts and our development of a 1,2,3-triazolium salts catalyzed transannular C-acylation of enol lactones for the synthesis of chiral spirocyclic 1,3-diketones.This catalytic enantioselective reaction provided a rapid entry to a wide range of enantioenriched spirocyclic 1,3-diketones,albeit in moderate to high yields and enantioselectivities.A probable catalytic model for the generation of enantioselectivity in the transannular C-acylation event was also suggested.In chapter 3:The research background of Steglich or Steglich-type rearrangement was introduced.Taking advantage of chiral isothiourea catalysis,we have developed a catalytic enantioselective Steglich-type rearrangement of enol lactones for the synthesis of spirocyclic 1,3-diketones.The asymmetric acyl transfer reaction provided a highly enantioselective approach to spirotricyclic?,??-diketones.