Construction Of Chiral Multi-Substituted ?-Lactones Via Novel Oxidative Lactonlizations

The development of new and practical strategies for the construction of chiral?-butyrolactones has consistently been of great interest to synthetic chemists,owing to their presence in a variety of natural and synthetic molecules which display an impressive range of biological activities,and their use as a prominent class of chiral building blocks for the synthesis of diverse pharmaceuticals and fine chemicals.In this thesis,four main types of novel oxidative?-butyrolactonization reactions based on sodium chlorite?NaClO₂?system-mediated cascade sequences have been described to synthesizechiralmulti-substituted?-butyrolactonesandspirooxindole-?-butyrolactones.This dissertation consists of six chapeters.In the chapter one,the progress of constructing chiral?-butyrolactones via asymmetric catalysis and chiral auxiliary induction was reviewed briefly.And the research background and plan were introduced.In the second chapter,a new and green NaClO₂/DBDMH combination-mediated oxidative?-butyrolactonizations of chiral?,??-dicarbonyl-substituted aldehydes was developed for the first time.LC-HRMS analysis suggested that this novel oxidative?-butyrolactonization reaction probably via a simultaneous Pinnick oxidation/halogenation and next intramolecular substitution cascade process.The halogenating agent should be the in situ generated ClO^-and additive DBDMH.This new reaction is amenable to a multi-gram scale-up with high yield.Encouragingly,this reaction had hardly any erosion in enantioselectivity.In the third chapter,for the first time,chiral 3-oxindolepropionic aldehydes,Michael adducts of 3-olefinic oxindoles with aliphatic aldehydes,are directly converted to spirocyclic oxindole-?-lactones solely by sodium chlorite via a tandem Pinnick oxidation/chlorination/substitution sequence.This reaction uses waste ClO^-generated in the initial Pinnick oxidation as an eco-friendly halogenating agent for the subsequent chlorination,and then it utilizes the byproduct OH^-formed in the chlorination to facilitate the final internal substitution.The presented strategy features mild reaction conditions,excellent yields and enatioselectivities?up to 97%yield and 99%ee?.Importantly,most of the major stereoisomers are obtained in acceptable yields by simple recrystallization or column chromatograph.This new reaction is also amenable to gram scale-up with good reaction selectivities.Moreover,spirocyclic oxindole-paraconic acid,a new type of potentially bioactive compound,was obtained by simple hydrolysis with trifluoroacetic acid?TFA?.In the fourth chapter,another new oxidative?-butyrolactonization reaction for synthesis of rare chiral?-?o-hydroxybenzoyl?-butyrolactones was developed using chromen-?-lactols,Michaeladdition/hemiacetalizationproducts of 4-hydroxy-coumarin with?,?-unsaturated aldehydes,only in the presence of NaClO₂.The desired?,?-disubstituted butyrolactones were obtained in moderate to good yields?upto84%yield?probably via an unprecedentedcascadePinnick oxidation/chlorination/substitution/hydrolysis/decarboxylation sequence.On the basis of this methodology,the enantioselective synthesis of natural product?2R,3R?-Phenatic Acid B and its analogue will be shorten to 5 steps?11 steps for known methoed?.In the fifth chapter,a diastereodivergent strategy was presented for constructing chiral?,??-dicarbonyl-substituted butyrolactones bearing two stereocenters via NaClO₂/LiBrorNaClO₂/NBScombination-mediated Pinnickoxidation/halogenation/internal substitution cascade sequence.Either the anti or syn?-butyrolactones can be accessed with moderate to good diastereoselectivities,depending on the choice of additives?LiBr or NBS?.On the basis of this methodology,the formal total synthesis of natural products?+?-Nephrosteranic acid and?+?-Nephrosterinic acid were completed,and the formal total synthesis of?+?-Phaseolinic acid is conducting.In the sixth chapter,the research contents of this dissertation were summarized and the development trend of NaClO₂ system-mediated oxidative lactonizations and the necessity of developing alternative ones were outlooked.