Transcript “ ”  Practical and High Yielding Oxidation of

“Practical and High Yielding Oxidation of Hydroxyketones to -Diketones Using IBX”
Samuel L. Bartlett
HHMI Undergraduate Research Symposium
September 14th, 2011
Importance of -diketones
A motif in biologically active compounds:
Useful in the Knovenagel Condensation:
Antonioletti, R.; Bovicelli, P.; Malancona S.Tetrahedron 2002, 58, 589-596
Importance of -diketones
A motif in biologically active compounds:
Useful in the Knovenagel Condensation:
Antonioletti, R.; Bovicelli, P.; Malancona S.Tetrahedron 2002, 58, 589-596
-Diketone Synthesis
-hydroxycarbonyl derivatives may:
(a) suffer fragmentation via
retro-aldol processes
(b) undergo -elimination of H2O
12 other examples with average yield of 59%
Smith, A. B.; Levenberg, P.A. Synthesis 1981,7, 567.
(c) undergo further oxidation due
to the enolic nature of the
derived product.
-Diketone Synthesis
-hydroxycarbonyl derivatives may:
(a) suffer fragmentation via
retro-aldol processes
(b) undergo -elimination of H2O
12 other examples with average yield of 59%
Smith, A. B.; Levenberg, P.A. Synthesis 1981,7, 567.
(c) undergo further oxidation due
to the enolic nature of the
derived product.
-Diketone Synthesis
-hydroxycarbonyl derivatives may:
(a) suffer fragmentation via
retro-aldol processes
(b) undergo -elimination of H2O
12 other examples with average yield of 59%
Smith, A. B.; Levenberg, P.A. Synthesis 1981,7, 567.
(c) undergo further oxidation due
to the enolic nature of the
derived product.
Garugamblin I
Finney, N.S; More, J.D. Org. Lett. 2002, 4, 3001-3003
Garugamblin I
Finney, N.S; More, J.D. Org. Lett. 2002, 4, 3001-3003
Mechanism of Oxidation
Comparative Analysis
-Diketones do not react with IBX
Why is IBX superior to other oxidants?
1. IBX is a slow and very mild oxidant.
• Heterogenous in EtOAc.
• Reaction time of 3 to 12 hours.
• Prevents over oxidation.
-diketones are over oxidized by DMP:
Starting
material
After
work-up
+ DMP, 5 minutes
SXR
-Diketones do not react with IBX
Why is IBX superior to other oxidants?
1. IBX is a slow and very mild oxidant.
• Heterogenous in EtOAc.
• Reaction time of 3 to 12 hours.
• Prevents over oxidation.
-diketones are over oxidized by DMP:
Starting
material
After
work-up
+ DMP, 5 minutes
SXR
-Diketones react on silica gel
Why is IBX superior to other oxidants?
2. -diketones are reactive on standard silica gel columns.
• Chromatographic purification leads to low mass recovery.
• Lewis acidic silica gel may promote enolization and subsequent
reactions of -diketones.
• The IBX protocol requires only simple filtration.
IBX
Swern
DMP
-Diketones react on silica gel
Why is IBX superior to other oxidants?
2. -diketones are reactive on standard silica gel columns.
• Chromatographic purification leads to low mass recovery.
• Lewis acidic silica gel may promote enolization and subsequent
reactions of -diketones.
• The IBX protocol requires only simple filtration.
IBX
Swern
DMP
Scope of Reaction
Bartlett, S.L.; Beaudry, C.M. Manuscript submitted to J. Org. Chem.
Curcumin
curcumin
Current Limitations
1. Hetero-aromatic β-hydroxyketones have not been converted in high yield:
2. Loss of mass with low molecular weight diketones:
Summary
1. IBX is superior to other common oxidants for the transformation of
-hydroxyketones to -diketones.
2. IBX can be used to oxidize a wide variety of -hydroxyketones in
excellent yield, including α-iodo substituted compounds.
Future Work
1.Use IBX oxidation to form curcumin:
2.Explore the oxidation of hetero-aromatic -hydroxyketones:
3.Probe the reactivity of α-iodo-β-diketones:
Acknowledgements
Prof. Chris Beaudry
The Beaudry Group
HHMI Program
URISC Program
Cripps Scholarship
Cambridge Isotope Laboratories