Synthesis of (±)-epi-Stegobinone Utilizing...
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Synthesis of (±)-epi-Stegobinone Utilizing Silacyclopropanes as Synthetic Intermediates Calad, S. A.; Cirakovic J.; Woerpel, K.A. J. Org. Chem. 2007, 72, 1027-1030. O O O Presented by Melissa Sprachman, 1/29/07
Transcript of Synthesis of (±)-epi-Stegobinone Utilizing...
Synthesis of (±)-epi-StegobinoneUtilizing Silacyclopropanes as
Synthetic Intermediates
Calad, S. A.; Cirakovic J.; Woerpel, K.A. J. Org.Chem. 2007, 72, 1027-1030.
O
O
O
Presented by Melissa Sprachman, 1/29/07
Presentation Overview
*Background and Significance
*Brief Insight into Woerpel’s Silacyclopropane Methodology
*Woerpel Group Synthesis of (±)-Epi-Stegobinone
*Brief Comparison to Another Stegobinone Synthesis
Stegobium paniceum(Linnaeus)
Stegobinone Background
-Sex pheremone produced by the female drugstore beetle
-Absolute configuration determined by stereocontrolledsynthesis (Hoffmann, 1979: Tetrahedron Lett. 1979,4653-4656).
-Epimer of Stegobinone; repellent to the male of thespecies
O
O
O
(2S, 3R, 1'R)-Stegobinone
1'2
3
O
O
O
(2S, 3R, 1'S)-Stegobinone
1'
3
2
Image © Degesch
Polypropionate Natural Products
O
O
O
O
O
Membrenone-Aisolated fromPleurobranchus Membranaceus
Tetrahedron Lett. 1993, 34, 6791-6794
O
O
O
O
Vallartanone AIsolated fromSiphonaria maura
J. Org. Chem. 1989, 54, 5374-5377
OH
O
O
(-)-MaurenoneIsolated from Siphonaria maura
Recent synthesis reported by Perkins:J. Org. Chem. 2006, 71, 117-124.
Silacyclopropane Insertion Methodology
-Takes advantage of strain energy release:
SEsilacyclopropane = 40.5 kcałmol [J. Phys. Chem. 1989, 93, 1584-1585]
-Stereoselective: stereochemistry of the initial silacyclopropane species is retained
-Regioselective: dependent on metal catalyst
-Copper salts --> insertion at the more substituted carbon
-Zinc salts --> insertion at the less substituted carbon
Acc. Chem. Res. 2000, 33, 813-820.
Si
RR
R1 R2
+
O
X H
OSi
R
R
R1
R2
XR1
OH OH
X
R2
[O]
Base or Metal cat.
* * **
* **
*
Silylene Extrusion Pathway
J. Org. Chem. 2004, 69, 4007-4012
J. Am. Chem. Soc. 2004, 126, 9993-10002
Sit-Bu
t-Bu
Ln[Ag]OTf
Si[AgLn]
TfO
t-Bu t-Bu
Si [AgLn]
t-Bu
t-BuOTfR
[AgLn]Si
R
TfO
t-Bu t-Bu
Si
t-Bu
t-Bu
Copper Catalyzed Carbonyl Insertion
Acc. Chem. Res. 2000, 33, 813-820
Me
NH
O
BnSi
t-But-Bu
i-Pr
+10 mol % CuI
CH2Cl2-78oC to 22oC
72%
OSi
NBn
Me
t-Bu
t-Bu
i-Pr
one stereoisomer> 99:1 regioselectivity
Si
t-But-Bu
CuI
Cu
Si
t-Bu
t-BuI
Via
Si
Cu I
t-Bu
t-Bu
Me
NH
O
Bn
Cu
Si
t-Bu
t-Bu
O
H
N
Me
BnI
OSi
NBn
Me
t-Bu
t-Bu
Example ofRegioselectivity:
Retrosynthetic Analysis
OHOH O OPG
Silacyclopropane insertion methodology
Aldol
O
O
O
OSi
t -Bu
t-Bu O
Si
t-But-Bu
Synthesis of (±)-Epi-Stegobinone by Woerpeland Coworkers
SnBr4, 95%
Et
OSiMe3
OSi
t -Bu
t-Bu O
97:2:1 dr
OSi
OAc
t-Bu
t-Bu
Sit-Bu
t-Bu
AgOC(O)CF3
Si
t-But-Bu
(1-2 mol %)
N
CHO
Bn Me
CuI (20 mol%)
CuSO4 (aq); Ac2O
OSi
OAc
t-Bu
t-Bu
74% from cis-butene
Explanation of Selectivity of the Enol SilaneAddition
OSiMe3
Et
OSiMe3
Et
“Inside Attack”
Favored TS
Nucleophilic approachthrough an antiperiplaner TS
Si OMe
Me
Si O
MetBu
tBu
Me
tBu
tBu
O
H
MeH
Et OSiMe3
t-Bu2Si
J. Org. Chem. 2002, 67, 2056-2064.
OSi
t -Bu
t-Bu O
1) t-Bu2Si(OTf)2
2,6-lutidine, 80%
2) O3, PPh3 99%
OOSi
O
t-Bu t-Bu
O
SnLnO
Me
H
Et
O
O
Si
H
Met-Bu
t-BuOO
SiO
t-Bu t-Bu
Et
OH
anti, syn
LnSn
OO
Me
H
Et
HMe
OSi
O
t-Bu
t-Bu OOSi
O
t-Bu t-Bu
Et
OH
syn, synProposed Aldol Transition States :
OSi
t -Bu
t-Bu O 1) Ph3PCH3Brn-BuLi, 79 %
2) PhMe2C(OOH)KH, CsF, 94%
OHOH
Sn(OTf)2,-15oC, 2h
EtCHO, -78oC, 2h
97%
N EtOO
SiO
t-Bu t-Bu
Et
OH
85:15 dr
* *
i-Bu2AlH
93% O
OH
OH
O
O
O
X-Ray Crystal Structure Confirmed theIndicated Stereochemical Relationship
Dess-Martin
48%
17 Steps, 8.8%Overall Yield
OOSi
O
t-Bu t-Bu
Et
OH
1) Ac2O, 97%2) HF-pyridine3) TBDMSCl
58% over 2 steps
OOHO
Et
OAc
SiMe2tBu
1) (CoCl)2, DMSO, Et3N
2) CF3CO2H
87% over 2 steps O
O
OAc
Completion of Synthesis and StereochemicalDetermination
Brief Overview of Another StegobonineSynthesis
Matteson et al. J. Am. Chem. Soc. 1996, 118 4560-4566
-Achieved asymmetric synthesis of the natural epimer Stegobinone, deriving allstereocenters from a chloro boronic ester intermediate species:
B
OBn Cl
O
O H2O2
pH 8-9H
OBn O
B
O
O
O
BBNOTf
Et2NCHMe2
-78oC to 0oC
H
OBn O
OBn B
O
O
O
O
O
O
B O
O
OH-78oC to 0oC
18 steps, 12.5% overallyield (no ee’s listed)
Conclusions
*Woerpel and Co-workers synthesized the epimer of theirtarget molecule in 17 steps and 8.8% yield.
*Diastereoselectivity within the synthesis was accomplishedvia Woerpel’s silacyclopropane methodology.
*This initial success indicates that the silacyclopranes may beused as synthetic intermediates in other natural productsyntheses.
*Problems involved in using the silacyclpropanemethodology were revealed, namely functional grouptolerance under Si-C bond oxidation conditions.
