Dissertation Information for Heilam WongNAME:
DEGREE:
DISCIPLINE:
SCHOOL: ADVISORS: COMMITTEE MEMBERS: MPACT Status: Fully Complete Title: Design, synthesis and resolution of a chiral, non-racemic organometallic chiron: Asymmetric total syntheses of tetrahydropyridine based alkaloids Abstract: An enantiopure 5-oxo-([eta]-2,3,4)-dihydropyridinyl molybdenum complex has been designed as a versatile organometallic chiron for the synthesis of piperidine based alkaloid natural products and biologically active pharmaceuticals. A scalable synthetic route starting from benzyl glycine ether ester has been developed. After installation of a chiral non-racemic ( S )-1-phenylbutoxycarbonyl protecting group, the key scaffold was successfully resolved in large quantity and in high enantiomeric excess. A series of 2,3,6-trisubstituted tetrahydropyridinyl molybdenum complexes were prepared in five steps from the platform complex. Organocerium addition of the key scaffold followed by dehydration afforded an ene-allyl complex. The key intermediate exocyclic olefin complex was synthesized efficiently through a one-pot regioseletive methoxy abstraction/nucleophilic addition/deprotonation sequence from the ene-allyl complex. A cascade protonation/organocuprate addition of the exocyclic olefin complex furnished the synthesis of 2,3,6-trisubstituted tetrahydropyridinyl molybdenum complex. The exocyclic olefin complex also underwent a novel Prins reaction initiated cascade reaction to give perhydroquinolinyl molybdenum complex. Further studies should lead to a general approach to perhydroquinoline alkaloids. The 2,3,6-trisubstituted tetrahydropyridinyl molybdenum complexes underwent reductive or proto demetallation to afford 2,6- cis -3- trans -tetrahydropyridines and 2,3,6- cis tetrahydropyridines respectively. The generality, versatility and synthetic utility of this methodology have been demonstrated by the concise total syntheses of indolizidine (±)209I, indolizidine (±)-3- epi -219F, indolizidine (-)-251N, dehydroindolizidine (-)-233E and quinolizidine (-)-251AA. |
MPACT Scores for Heilam WongA = 0 Advisors and Advisees Graph |