Synthesis of 4-Aminocyclopentenones via Aza-Piancatelli Rearrangements Using Polymer-Bound Metal Catalyst Teresa Garay University of California, Santa Barbara Undergraduate Researcher, UCLEADS 2010 25 August 2010
Introduction: Natural Products Taxus brevifolia Taxol Anti-cancer alkaloid http://courses.washington.edu/bot113/conifer_slides/ source/taxus_brevifolia.html Need synthetic chemists to develop new methods to access biologically important molecules in the lab Wall, M.E. Med. Res. Rev. 1998 , 18 , 309. 2
Natural Products: A Sub-Family of Cyclopentane Motifs New methods of forming a cyclopentane scaffold containing nitrogen Cephalotaxine NK 1 inhibitor 1 Continuous flow chemistry: importance to industry “green” chemistry; more efficient and less waste http://www.californiagreensolutions.com /images/chemistry-globe.jpg 1 Finke, P.E. et al. Bioorg. Med. Chem. Lett. 2006 , 16, 4497-4499. 3
Where Are We Now? The Piancatelli rearrangement 1 Aza-Piancatelli rearrangements of furylcarbinols with amines to afford 4-aminocyclopentenones 1 Piancatelli, G. et al. Tetrahedron Lett. 1976 , 39 , 3555. 4
Polymer-bound Lewis Acid Catalyst Develop a comparative analysis: powder versus polymer-bound yield catalytic activity reaction efficiency catalyst degradation reaction time, etc. Powder scandium triflate catalyst OTf = triflate Polystyrene-bound scandium triflate catalyst 5
Materials Two different furylcarbinols to react with p -iodoaniline p -methoxyphenyl furylcarbinol phenyl furylcarbinol Polystyrene-bound Scandium triflate catalyst beads 6
Laboratory Process Rotary Flash Column TLC NMR Evaporator Chromatography 7
Laboratory Process Rotary Flash Column TLC NMR Evaporator Chromatography S C R 8
Laboratory Process Rotary Flash Column TLC NMR Evaporator Chromatography 9
Laboratory Process Rotary Flash Column TLC NMR Evaporator Chromatography 10
Laboratory Process Rotary Flash Column TLC NMR Evaporator Chromatography 11
Laboratory Process 12
p -Methoxyphenyl Furylcarbinol 13
Phenyl Furylcarbinol 14
Conclusion: What Does This Mean? Comparable yields indicate similar catalytic activity of polymer-bound catalyst beads to powder catalyst Catalyst beads can be recycled, as they show no degradation or instability after five trials Consistent yields suggest catalyst bead tolerance to air exposure for various lengths of time, and repeated heating cycles at 80 °C Potential for use of greater mole percentage to speed up rate of reaction 15
Future Direction Short-Term: Use new reactants in the rearrangement: different furylcarbinols and nitrogen species Mid-term: Investigate especially low-yielding reactions using polymer-bound catalyst in comparison to free, powder catalyst Long-term: Build a continuous flow reactor using solid supported polymer-bound catalyst Reaction column Next steps in with immobilized synthesis catalyst 16
Acknowledgements Dr. Javier Read de Alaniz and my mentor, Gesine Veits, for being patient and giving me the opportunity to contribute to their projects Thank you to the rest of the Read de Alaniz group for sharing their space and knowledge Jarred Engelking, Charles Frazier, Leoni Palmer, and Donald Wenz Arica Lubin and Matthew Crossley, and all the people who made this a program a success and a meaningful experience 17
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