Epoxide-Opening Cascades Promoted by Waterccc.chem.pitt.edu/wipf/Current Literature/Marija_2.pdf ·...
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Epoxide-Opening Cascades Promoted by Water Ivan Vilotijevic and Timothy F. Jamison Department of Chemistry, MIT Science, 2007, 317, 1189. Marija Manojlovic Wipf group current literature meeting 9-15-07 Marjia Manojlovic @ Wipf Group 1 10/29/2007
Transcript of Epoxide-Opening Cascades Promoted by Waterccc.chem.pitt.edu/wipf/Current Literature/Marija_2.pdf ·...
Epoxide-Opening CascadesPromoted by Water
Ivan Vilotijevic and Timothy F. JamisonDepartment of Chemistry, MIT
Science, 2007, 317, 1189.
Marija Manojlovic
Wipf group current literature meeting
9-15-07
Marjia Manojlovic @ Wipf Group 1 10/29/2007
“Ladder” polyether natural products
O
O
O
O
O
O
O
O
O
O
O
O
OH
HHH
HH
H
H
HH
H
Me
H
H
Me
H
HMe H
Me
brevetoxin A
-Potent neurotoxins
-Act by opening a sodium channels
-Toxic for marine organisms (kill fishin ng concentrations)
-Accumulate in shellfish and canpoison human consumers
-Synthetically challenging
-Speculative biosynthesis
Marjia Manojlovic @ Wipf Group 2 10/29/2007
Nakanishi cascade hypothesis-Structural pattern and stereochemical regularity imply certain degree ofsimplicity (repeating O-C-C units, trans stereochemistry across C-Cbonds of ring junction)
-Nakanishi: Transformation of polyepoxide into a ladder polyether viacascade of epoxide-opening events
Science, 2007, 317, 1189.
Marjia Manojlovic @ Wipf Group 3 10/29/2007
Epoxide opening: Baldwin rules
O
Me
HH
OH
BF3 OEt2
Et2O
O
OH
Me
H H
98%
O
Me OH
-Epoxide opening reactions of this type generally favor smaller heterocycle,arising from spiro transition state, over heterocycle arising from fusedtransition state.
O
H
MeH
OH
BF3 OEt2
Et2O
OH
H
Me H
O
84%
O
OHMe
16%
Aus. J. Chem. 1973, 26, 2521.
Marjia Manojlovic @ Wipf Group 4 10/29/2007
Epoxide opening: endo vs. exocyclization
O
H
RH
OH
CSA
OR
HOH
H
+ OHR
HOH
R = -CH2CH2CO2Me 0 100
-CH2=CH2 100 0 TMS (BF3 OEt2 as promoter) 95 5
OH
OCo cat.
O
OH
+O
OH
4.3 1
-To obtain desired, but disfavored, “fused” products:
-Directing groups:
-Transition metal catalysts:
t-Bu
t-Bu
O
N N
O
t-Bu
O
Co
OAc
H H
O
2
Org. Lett, 2003, 5, 2339. JACS 1989, 111, 5330. ACIE 1999, 38, 2012.
Marjia Manojlovic @ Wipf Group 5 10/29/2007
Jamison’s previous work: TMS asdirecting group
-Lewis acid catalyzed reaction leads to THF product, while base catalyzedreaction leads to desired THP product
-The loss of one TMS group change the course of investigation towards“disappearing” directing group
Org. Lett, 2003, 5, 2339.
Marjia Manojlovic @ Wipf Group 6 10/29/2007
Jamison’s previous work: templatepromoted reaction
-Trans-bicyclo[4.4.0] decanes are typically less strained than trans-bicyclo[4.3.0]nonanes
OMe
O
H
HOH
MeO
HO
O O
OO
H
H H
Me
H
H+
O
HO
Me
H
HH
M e
HH
H+
O
HO
Me
H
H
OO O
H
HH
H
M e
OH
H
H+H+
H
HH
O
MeH
H
H
O
O
HO
Me
H H
H H
-H+
-H+-H+
-H+
O
O
Me
HOH
H
H
attac h templatem in im ize etropic e ffects
and
enhance enthalpic e ffects
Science, 2007, 317, 1189.
Marjia Manojlovic @ Wipf Group 7 10/29/2007
Jamison’s previous work: disappearingdirecting group
-Trans-bicyclo[4.4.0] decanes are typically less strained than trans-bicyclo[4.3.0]nonanes
JACS 2006, 128, 1056.Marjia Manojlovic @ Wipf Group 8 10/29/2007
Jamison’s previous work: directing-group-free epoxide-opening cascades
Jamison’s plan
However:
Synlett, 2006, 2329.
Marjia Manojlovic @ Wipf Group 9 10/29/2007
Organic solvents failed-watersucceeded
-Wide range of solvents, acids and bases were tested
- Maximum THP:THF selectivity (10:1) obtained at pH near 7, which impliedthat water might be a suitable solvent for the reaction
-In less polar solvents (CH2Cl2, toluene) low conversion is observed and inpolar aprotic solvents selectivity is reduced (≤3:1)
-Deionized water as a solvent provides the highest selectivity (11:1)
-Only other acceptable promoters are ethylene glycol (9:1) and methanol (8:1)
O
O
HO
Me
H H
H H
O
O
Me
HOH
H
H
OMe
O
H
HOH
Science, 2007, 317, 1189.
Marjia Manojlovic @ Wipf Group 10 10/29/2007
Epoxide-opening cascades
O
ROH
H
H
O
HOH
HMe
O
HOH
HM e
O
O
O
TB SOH
H
Me
O
HOH
H
MeO
O
O
Cs2CO
3, CuI,
NaI, DMF, 92%
M e
Br
Cs2CO
3, CuI,
NaI, DMF, 92%
M eBr
1. L i, NH3
2. Shi epoxidation
1. L i, NH3
2. Shi epoxidation
3. TB AF, THF
50%
35%
4:1 dr
3:1 dr
O
HOH
HMe
O
O
O
O
O
HO
Me
H H H
H H H
H2O
70°C, 24h
60% isolated yield (87% yield per epoxide opening)
O
HOH
H
MeO
O
O
O
O
O
H H H
H H H
OMe
HO
H
H
H2O
70°C, 24h
53% isolated yield (89% yield per epoxide opening)
Science, 2007, 317, 1189.
Marjia Manojlovic @ Wipf Group 11 10/29/2007
Proof for Nakanishi hypothesis• Development of all-THF epoxide-opening cascades was taken as a support
for Cane-Celmer-Westley hypothesis for biosynthesis of monensin
• All-THP cascade shown in this paper can be taken as a support forNakanishi hypothesis for ladder polyether biosynthesis.
• Template THP ring can be used as a surrogate for conformation constraintsin enzyme active site
• Water as a promoter may imply hydrogen bond activation in the enzymesurroundings
Proposed biosynthesis
O
O
O O
Me
Me
1.KOH 2. HCl
3. aceone, H+
O O O
O
Me
Me
HH Me
Me
O
Schreiber’s synthesis
Science, 2007, 317, 1189. JACS 1983, 105, 3594.
Marjia Manojlovic @ Wipf Group 12 10/29/2007
The role of water: assumptions
-Activation of an epoxide andHO-group can be achieved intwo ways (A and B).
-Model A accounts for theregioselectivity
- Model B is analogous toepoxide hydrolases TS(monensin biosynthesis)
Authors favor model A due to:
- relative simplicity
- results obtained with methanol and ethylene glycol (C and D)
Science, 2007, 317, 1189.
Marjia Manojlovic @ Wipf Group 13 10/29/2007
Conclusion
• “Templated, water-promoted, THP-selective epoxide-opening cascades provide a straightforward means forefficient and rapid assembly of ladder polyethers.”
• This work is a support for Nakanishi hypothesis forbiosynthesis of ladder polyether natural products.
Marjia Manojlovic @ Wipf Group 14 10/29/2007
