Samuel L. Bartlett HHMI Undergraduate Research Symposium September 14 th, 2011 “Practical and High...
-
Upload
alfredo-stokey -
Category
Documents
-
view
217 -
download
0
Transcript of Samuel L. Bartlett HHMI Undergraduate Research Symposium September 14 th, 2011 “Practical and High...
Samuel L. BartlettHHMI Undergraduate Research Symposium
September 14th, 2011
“Practical and High Yielding Oxidation of -Hydroxyketones to -Diketones Using IBX”
Importance of -diketonesA motif in biologically active compounds:
Useful in the Knovenagel Condensation:
Antonioletti, R.; Bovicelli, P.; Malancona S.Tetrahedron 2002, 58, 589-596
Importance of -diketonesA motif in biologically active compounds:
Useful in the Knovenagel Condensation:
Antonioletti, R.; Bovicelli, P.; Malancona S.Tetrahedron 2002, 58, 589-596
-hydroxycarbonyl derivatives may:
(a) suffer fragmentation viaretro-aldol processes
(b) undergo -elimination of H2O
(c) undergo further oxidation due to the enolic nature of the derived product.
-Diketone Synthesis
Smith, A. B.; Levenberg, P.A. Synthesis 1981,7, 567.
12 other examples with average yield of 59%
-hydroxycarbonyl derivatives may:
(a) suffer fragmentation viaretro-aldol processes
(b) undergo -elimination of H2O
(c) undergo further oxidation due to the enolic nature of the derived product.
-Diketone Synthesis
Smith, A. B.; Levenberg, P.A. Synthesis 1981,7, 567.
12 other examples with average yield of 59%
-hydroxycarbonyl derivatives may:
(a) suffer fragmentation viaretro-aldol processes
(b) undergo -elimination of H2O
(c) undergo further oxidation due to the enolic nature of the derived product.
-Diketone Synthesis
Smith, A. B.; Levenberg, P.A. Synthesis 1981,7, 567.
12 other examples with average yield of 59%
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 IBXWhy 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.
S X R
Startingmaterial
Afterwork-up
-diketones are over oxidized by DMP:
+ DMP, 5 minutes
-Diketones do not react with IBXWhy 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.
S X R
Startingmaterial
Afterwork-up
-diketones are over oxidized by DMP:
+ DMP, 5 minutes
-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 Work1.Use IBX oxidation to form curcumin:
2.Explore the oxidation of hetero-aromatic -hydroxyketones:
3.Probe the reactivity of α-iodo-β-diketones:
AcknowledgementsProf. Chris Beaudry
The Beaudry Group
HHMI ProgramURISC ProgramCripps Scholarship
Cambridge Isotope Laboratories