Synthesis of 4-Aminocyclopentenones via Aza-Piancatelli - - PowerPoint PPT Presentation

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

Wall, M.E. Med. Res. Rev. 1998, 18, 309.

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 Need synthetic chemists to develop new methods to access

biologically important molecules in the lab

http://courses.washington.edu/bot113/conifer_slides/ source/taxus_brevifolia.html

Taxol Taxus brevifolia

Anti-cancer alkaloid

Natural Products: A Sub-Family of Cyclopentane Motifs

1Finke, P.E. et al. Bioorg. Med. Chem. Lett. 2006, 16, 4497-4499.

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 New methods of forming a cyclopentane scaffold containing nitrogen  Continuous flow chemistry: importance to industry



“green” chemistry; more efficient and less waste

NK1 inhibitor1

http://www.californiagreensolutions.com /images/chemistry-globe.jpg

Cephalotaxine

Where Are We Now?

1Piancatelli, G. et al. Tetrahedron Lett. 1976, 39, 3555.

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 The Piancatelli rearrangement1  Aza-Piancatelli rearrangements of furylcarbinols with amines to

afford 4-aminocyclopentenones

Polymer-bound Lewis Acid Catalyst

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 Develop a comparative analysis: powder versus polymer-bound



yield



catalytic activity



reaction efficiency



catalyst degradation



reaction time, etc.

OTf = triflate Powder scandium triflate catalyst Polystyrene-bound scandium triflate catalyst

Materials

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 Two different furylcarbinols to react with p-iodoaniline



p-methoxyphenyl furylcarbinol



phenyl furylcarbinol

 Polystyrene-bound Scandium triflate catalyst beads

Laboratory Process

7 TLC Rotary Evaporator Flash Column Chromatography NMR

Laboratory Process

8 TLC Rotary Evaporator Flash Column Chromatography NMR

S C R

Laboratory Process

9 TLC Rotary Evaporator Flash Column Chromatography NMR

Laboratory Process

10 TLC Rotary Evaporator Flash Column Chromatography NMR

Laboratory Process

11 TLC Rotary Evaporator Flash Column Chromatography NMR

Laboratory Process

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p-Methoxyphenyl Furylcarbinol

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Phenyl Furylcarbinol

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Conclusion: What Does This Mean?

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 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

Future Direction

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 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 with immobilized catalyst Next steps in synthesis

Acknowledgements

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 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