Current Lit (05/22/2010)

Stereoretentive Suzuki-Muyaura Coupling of Haloallenes Enables Fully
Stereocontrolled Access to (−)-Peridinin
O
O
1'
O
11'
15'
HO
15
•
HO 3'
5
1
OAc
Eric M. Woerly, Alan H. Cherney, Erin K. Davis and Martin D. Burke
J. Am. Chem. Soc. (ASAP)
Current Literature
May, 2o1o
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Page 1 of 12
5/23/2010
Isolation and Structural Features:
•
Isolated in 1890 by Schütt from fresh-water dinoflagelletes (causing red-tide, > 106 cells/mL).
•
Later isolated from corals, clams and sea anemones.
•
OH
O
Dinoflagelletes - red pigment important for photosynthesis.
•
Full structure and assignment of Peridinin wasn’t achieved till 1971.
•
Interesting features:
•
•
•
•
AcO
O
O
OH
(+)-Peridinin
(Z)-γ-ylidenebutenolide moiety (anticancer activity?)
C37 nor-carotnoide
Stereogenic allene.
•
More recently, Peridinin suggested as 1O2 quencher; associated with atherosclerosis
rheumatoid arthritis and cancer, contributing to the aging process.
•
1st Total synthesis of (±)-Perdinin was completed over 100 years later by Ito (1993),
confirmed the structure.
Schütt, F. Ber. Deut. Bot. Ges. 1890, 8, 9.
Lieean-Jensen, S. at al J. Am. Chem. Soc. 1971, 93, 1823
Johansen, J. E.; Borch, G.; Liaaen-Jensen, S. Phytochemistry 1980, 19, 441
Yamano, Y.; Tode, C.; Ito, M. J. Chem. Soc. Perkin Trans. 1 1993, 1599.
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Katsumra’s Total Synthesis:
P+Ph3Br-
H
OH
•
3'
15
5
AcO
15'
•
1
O
10'
OH
OH
AcO
1'
2
CHO
O
TBSO
O
O
6a
4
HO
O
3
O
CO2Me
I
OH
O
OH
OTBS
O
5
I
OH
6b
O
O
O
O
OH
1. 5, nBuLi, 3 h
4
1. iPr2NEt, DMSO, 3h, r.t.
then AllylBr, r.t., 1 h, 70%
6b, Pd(Ph3P)4, Et3N,
CuI, r.t. 1 h
O
O
2. TPP, O2, hv, !78 oC TBSO
77%, 2 steps
2. CBr4, PPh3, Et3N,
! 60 oC, 1 h, 89%
3. TBAF, 81%
Pd
3
then HCO2H, 20 h,
49%
HO
Red.
Elimination
O
4
H
nBuLi
2. tBuOK, DMSO, r.t, 20 min
O
HO
1. 6a, Pd(Ph3P)4, iPr2NH,
CuI, r.t. 1 h, 84%
•
2. DIBAl, 0 oC, 80%
OH
HO
53%, 2 steps
OH
1. MnO2, Et2O, 3h
2. Ac2O, pyr,
86%, 2 steps
3
O
R
R'
Pd
Sonogashira
Coupling
2
3. NaBH4, MeOH, 98%
O
H
Al
O
R
R
O
R'
R
O
1. ClCH2P+Ph3Cl-,
! 30 oC, 3h
O
OAllyl
R
O
Ligand
Exchange
O
R' Pd Insertion
O
Pd
R'
R
“Domino Reaction”
Furuichi, N.; Hara, H.; Osaki, T.; Nakano, M.; Mori, H.; Katsumura, S. J. Org. Chem. 2004, 69, 7949.
Yamano, Y.; Tode, C.; Ito, M. J. Chem. Soc. Perkin Trans. 1 1993, 1599.
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Page 3 of 12
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Katsumra’s Total Synthesis cont.
OH
O
MnO2
3
OH
OHC
Et2O
O
O
NaHMDS
O
•
!78 oC dark, 5 min
AcO
2
N
H
1. 7, DIAD. PPh3, 78%
S
O2
•
2. (NH4)6Mo7O24,
aq H2O2, 89%
O
E/Z 1/3
S
Benzene
r.t. 3 d
E/Z > 5/1
50% from aldehyde
OH
AcO
N
O
OH
HS
S
7
OH
O
•
C33
O
O
OH
AcO
OH
O
•
C35
O
O
OH
AcO
OH
O
•
AcO
OH
O
O
C39
• Peridinin posses large static dipole moment facilitating energy transfer.
Katsumura at el Org. Lett. 2009, 11, 5006.
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Page 4 of 12
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Brückner’s Approach to the Butenolide Moeity:
4
O
O
O
O
1
CO2Et
EtO2C
O
MeO2C
O
OH
(!)-diethyl tartrate
+
MeO2C
O
OH
Br
MeO2C
O
1
O
4
O
O
OHC
Bu3Sn
MeO2C
2
4-deoxy-4
O
O
.
O
O
3 steps
CO2Et
EtO2C
O
OMe
MeO2C
O
O
N
Me
O
1. NaBH4 (8.0 eqv), 98%
2. Swern [O], 90%
3. NaH, THF, 90% E:Z =95:5
O
PhO
P
PhO
Br
MeO2C
CO2Et
O
Amberlyst 15, MeOH
reflux, 28 h, 95%
Br
CO2Et
OH
1. O3, MeOH
MeO2C
2. NaBH4
3. Sharpless,
67%, 99.8%ee
4. Swern [O], 99%
1. LDA, TMSCHN2
O
OHC
O
2. Bu3SnH, Pd(PPh3)4
+
Bu3Sn
Br
MeO2C
O
O
1. CuI, Pd2dba3, P(2-furyl)3, 84%
2. DEAD, Ph3P, ! 30oC, 52%
1
• 2 was also prepared in the same fashion.
• Later in 2006, used the same methodology to complete the synthesis of Peridinin.
Olpp, T.; Brückner, R. Angew. Chem., Int. Ed. 2005, 44, 15533.
Olpp, T.; Brückner, R. Angew. Chem., Int. Ed. 2006, 45, 4023.
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Page 5 of 12
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Burke’s Work: MIDA Mask
• Highly unreactive.
• Very stable to most C-C conditions.
• Easily removable under mild conditions.
• Stable to silica chromatography and storage.
N
B
I
OMe OMe
H2N
2
O
OMe OMe
H2N
1 Crocacin C
B
O
SnBu3
Br
O
N
H
3
4
N
B
O
O
O O
PMBO
OH OH
O
O
O O
N
3
1. Me3OBF4,
proton sponge, 82%
2. CAN, 77%
O
O
O O
CuI, CsF, DMF
N
B
OH
OMe OMe
2, Pd(PPh3)4
62%
1. DMP, 97%
O
O
O O
B
H2N
O
OMe OMe
O
O
O O
4, Pd(OAc)2
1
SPhos, K3PO4
77%
2
2. CHI3, CrCl2
THF:Dioxane, 74%
• Nine linear steps synthesis of crocacin C
Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716.
Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2008, 130, 14084.
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Page 6 of 12
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Title Paper - Key Reaction:
Stereoretentive SM cross-coupling
O
O
HO
•
O
HO
OAc
Iterative Cross Coupling (ICC)
N
B
O
TBSO
N
O O
O O
B1
B
I
O
N
O
B
Br
B2
O
O
O O
O O
O O
B3
I
H
TMSO
•
OAc
B4
Key Reaction:
PhB(OH)2, Ag2O
H
H
Pd2(dba)3, Ligand
H
•
R
X
THF:H2O, rt, 1.5 h
R
Ph
(R)
(R)
R C C C X
H
H
H
•
PhZn2 or PhZnCl
cat. Pd(PPh3)4
R C C C Ph
H
H
Woerly, E. M.; Cherney, A. H.; Davis, E. K.; Burke, M. D. J. Am. Chem. Soc. (ASAP)
Elsevier, C. J.; Vermeer, P. J. Org. Chem. 1985, 50, 3042.
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Page 7 of 12
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Pd(0)-Catalysed Phenylation of 1-Haloallenes:
H
Inversion
H
Ph
•
X = Cl or Br
R
Retention
H
X=I
R
H
H
•
R
(R)
X
H
•
Ph
PdL4
Inversion:
H
X
•
R
H
R C C C Ph
H
H
PdL2
H
!PdL2
R
X
•
H
SN2'
R
anti
H
H
X
[1,3]-shift
H
L
Pd
L
PdL2
X
Ph
Retention:
H
I
•
R
(R)
H
halide transfer
L
H
Pd(PPh3)4
•
C C C H
H
R
cage
Pd
H
L
L
X
Pd
Pd
R C C C
H
L
L PdI I
R C C C X
H
H
H
•
R
PdL2
PdL2
R C C C
H
L
H
L
H
I
L
(R)
ZnXY
PhZnY
(retention)
• Oxidative addition to Pd decreases I > Br > Cl, as in vinyl halides.
• Heavier metals, group VIII show affinity to heavy halogens.
• Possible radical intermediate in which recombination rate is faster.
Proposed catalytic cycle
Elsevier, C. J.; Vermeer, P. J. Org. Chem. 1985, 50, 3042.
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Page 8 of 12
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Application in Synthesis:
Lera’s Synthesis of Peridinin:
H
1. CuBr, NH4Br
HBr, Et2O, 85%
•
Bu3Sn
SO2BT
[Pd(PhCN)2Cl2],
Br
SO2BT
•
6'
OH
HO
2. Ac2O, pyr, 85%
(iPr)2NEt, DMF:THF
64%
OH
AcO
H
•
PdL2X
•
H
superfacial
1,3-shift
PdL2X
•
OH
Transmatalation then
Reductive Elimination
Product with Retention
OH
AcO
"PdL2"
anti-SN2'
displacement
of Br
HO
6'-epi-Peridinin
OH
H
Oxidative
addition
X
OH
AcO
AcO
Transmatalation then
PdL2X Reductive Elimination
Product with Inversion
OH
AcO
Haloallene Natural Products:
O
Br
Br
H
H
OH
H
O
OMs
O
H
H
H
LiCuBr2
O
H
O
H
•
H
H
Br
O H
Br
H
Br
Br
O H
Br
H
O H
•
H
H
Br
Laurellene
Panacene
Vaz, B.; Domínguez, M.; Alvarez, R.; de Lera, A. R. Chem.-Eur. J. 2007, 13, 1273.
K. S. Feldman, C. C. Mechem, L. Nader, J. Am. Chem. Soc. 1982, 104, 4011.
M. T. Crimmins, E. A. Tabot, J. Am. Chem. Soc. 2000, 122, 5473.
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Page 9 of 12
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Title Paper: Forward Synthesis
N
Stereoretentive SM cross-coupling
O
O
B
O
HO
Iterative Cross Coupling (ICC) TBSO
•
O
HO
N
O
O
O O
B
I
B1
B3
O
OAc
H
N
O
B
Br
B2
O
O
O O
I
O O
O O
TMSO
•
OAc
B4
O
B
pinBH
O
Cy2BH
TBSO
81%
O
Me
N
O
HO2C
N
B
CO2H
O
DMSO, 3 cycles
TBSO
TBSO
O
O
O O
B1
73%
O
O
Br
Br
1
N
B
O O
O O
Bu3SnH
Mo. cat
THF
84%
O
N
Bu3Sn
B
O
O
O O
Mo cat = [Mo(allyl)Br(CO)2(CH3CN)2]
THF
77%
N
O
1, Pd2(dba)3, Ph3As
B
Br
B2
O O
O O
Structure confirmed by X-ray
Woerly, E. M.; Cherney, A. H.; Davis, E. K.; Burke, M. D. J. Am. Chem. Soc. (ASAP)
Furuichi, N.; Hara, H.; Osaki, T.; Nakano, M.; Mori, H.; Katsumura, S. J. Org. Chem. 2004, 69, 7949.
Zhang, H. X.; Guibe, F.; Balavoine, G. J. Org. Chem. 1990, 55, 1857.
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Page 10 of 12
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Total Synthesis of (-)-Peridinin: Final Steps
N
N
B
1. Br2, CH2Cl2
O
O
O O
2. DBU, MeCN
B
Br
67%
1. 2, PdCl2(PPh3)2,
DMF:THF, 74%
O
O
2. I2, MeOH, 77%
O O
B
I
O
O
O O
O
B
O
TBSO
1. NaOH, THF:H2O, 95%
O
O
O O
2. B2, Pd(OAc)2, XPhos,
K3PO4, Tol:THF, 79%
O
B
Br
B2
O
O
O
TBSO
O
O
O O
I
B3
SnBu3
Et3Ge
O
O
O O
2
1. pinacol, NaHCO3,
MeOH, 99%
2. B3, PdCl2(PPh3)2,
Ag2O, DMSO, 45%
O
O
O O
N
B
TBSO
B
B
N
O
O
2. I2, MeOH, 75%
N
O
N
N
1. 2, Pd(PPh3)4,
CuTc, DMF, 58%
N
O
O
O O
O
1. B4, Pd(OAc)2, XPhos,
NaOH, THF:H2O, 60%
O
2. HF.pyr, THF, 65%
HO
H
I
HO
•
O
OAc
(-)-Peridinin
TMSO
•
OAc
B4
PCy2
iPr
iPr
= XPhos
iPr
Woerly, E. M.; Cherney, A. H.; Davis, E. K.; Burke, M. D. J. Am. Chem. Soc. (ASAP)
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Page 11 of 12
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Conclusion:
•
Synthesis of (+)-Peridinin focused on a late stage construction of olefins, which proved problematic due to
the E/Z isomerization.
•
Burke’s strategy proved successful in avoiding the isomerization using a different approach, SM cross coupling, in
his synthesis of (-)-Peridinin.
•
Combination of bulky substituent and ligand promoted stereoretention in SM cross coupling of Iodo-allenes.
•
Using a more stable MIDA boronates which has a lot of advantageous in the modern synthetic chemistry.
•
Achieved 1st Stereoselective total synthesis of (−)-Peridinin.
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Page 12 of 12
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