Studies Of Tandem Reactions Consisting Of Smiles Rearrangement And Intramolecular Nitrone-alkene Cycloadditions

This dissertation is divided into two parts. In part one, the chiral induction effect intandem iminium cyclization-Smiles rearrangement reactions and tandem nucleophilicsubstitution-Smiles rearrangement reactions were investigated. In part two,isoxazolidine-fused8-membered heterocycles were synthesized via an intramolecularnitrone–alkene cycloaddition.Tandem reactions consisting of Smiles rearrangement are summarized as thebackground in chapter one. These tandem reactions are convenient and efficientmethods for synthesis of many types of heterocyclic compounds.Based on our previous work on tandem iminium cyclization-Smiles rearrangementreactions, we studied the chiral induction effect in this tandem reaction. We designednovel tandem hydroxy nucleophilic substitution-Smiles rearrangement reaction for thesynthesis of pyrrolo[1,2-f]pteridine compoundsIn chapter two, we studied the α-substituent (R1=Me, i-Pr, Ph) chiral aminoalcohols on stereoselectivity in the tandem iminium cyclization-Smiles rearrangementreactions. Oxidation and tandem iminium cyclization-Smiles rearrangement reactionsof the alcohol (R1=Me) provided pyrrolo pteridine product in good yield. No Smilesrearrangement products were obtained when R1=i-Pr, Ph presumably due to sterichindrance.Aromatic amines are suitable substrates for the acid-catalyzed tandem nucleophilicsubstitution-Smiles rearrangement reaction. A large of ortho-substituent prevented aromatic amines from undergoing Smiles rearrangement. Aliphatic amines are notsuitable presumably because their nitrogen atom protonated.In chapter three, the olefin-nitrone cycloaddition reaction was introduced asbackground. The intramolecular olefin-nitrone1,3-dipolar cycloaddition can form twonew rings simultaneously with fused or bridged polycyclic isoxazolidines ofconsiderable complexity in high levels of regio-and stereocontrol. Thus far, theintramolecular nitrone-alkene cycloaddition reactions have been successfullyemployed for the construction of4-to7-membered ring fused by isoxazolidines.However, few examples of syntheses of fused isoxazolidines containing an8-membered ring by intramolecular nitrone-alkene cycloaddition reaction have beenreportedThe correlation between the exo/endo ratio of the cycloadduts and the electronicprofile of the dipolarophile in the intermolecular nitrone-alkene1,3-dipolarcycloaddition has been investigated. It was reported that a strongelectron-withdrawing substituent of the dipolarophile led to an increased exo/endoratio of the cycloadduts. In C-alkyl nitrone cycloaddition reaction, the solvent can alsoaffect the endo/exo ratio of the cycloadduts.In the fourth chapter, an intramolecular nitrone-alkene cycloaddition yielded noveltricyclic8-membered ring with a fused isoxazolidine in good to excellent yields undermild reaction conditions. The details are summarized as follows:(1) The reaction of an aldehyde and N-substituted hydroxylamine providedcycloadduts under the optimal condition (NaOAc, DCM,25oC,0.01mmol/mL).(2) Cycloaddition reaction of substrates containing pyrimidine or pyridine yielded asingle cis product in high yield. A sterically hindered N-substituent of thehydroxylamine increased the reaction time and reduced the yield. The cycloadditionreaction of acrylamide substrate with3-position substituent provided good yield, butincreased reaction time.(3) Intramolecular nitrone-olefin [3+2] cycloaddition reaction of benzene basedsubstrates provided endo and exo products. The endo/exo ratio of the cycloadduts isrelated to electronic effects of dipolarophile substituent and the solvent.