Post on 06-Aug-2020
Stereoretentive Suzuki-Muyaura Coupling of Haloallenes Enables FullyStereocontrolled Access to (−)-Peridinin
Eric M. Woerly, Alan H. Cherney, Erin K. Davis and Martin D. Burke
J. Am. Chem. Soc. (ASAP)
Current LiteratureMay, 2o1o
OO
•OHO OAc
HO1'
1
5
3'
15
15'
11'
Sammi Tsegay @ Wipf Group Page 1 of 12 5/23/2010
•
AcO OH
OO
OOH
Isolation and Structural Features:
Schütt, F. Ber. Deut. Bot. Ges. 1890, 8, 9.Lieean-Jensen, S. at al J. Am. Chem. Soc. 1971, 93, 1823Johansen, J. E.; Borch, G.; Liaaen-Jensen, S. Phytochemistry 1980, 19, 441Yamano, Y.; Tode, C.; Ito, M. J. Chem. Soc. Perkin Trans. 1 1993, 1599.
(+)-Peridinin
• Isolated in 1890 by Schütt from fresh-water dinoflagelletes (causing red-tide, > 106 cells/mL).
• Later isolated from corals, clams and sea anemones.
• Dinoflagelletes - red pigment important for photosynthesis.
• Full structure and assignment of Peridinin wasn’t achieved till 1971.
• Interesting features:
• (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.
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Katsumra’s Total Synthesis:
1'
15
3'15
15'
10' CHOO
TBSO•
AcO OHO
O
OOH
•
H
AcO OH
OH
OOH
OO
HO
2
3
4
O
P+Ph3Br-
OTBS5
R
O AlH
OO
RSonogashiraCoupling
OO
R
R'
LigandExchange
OO
R
PdR'
OO
R Pd
R'
Pd Insertion
OO
RR'
Pd
Red.Elimination
3
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.
“Domino Reaction”
1. 5, nBuLi, 3 h
2. TPP, O2, hv, !78 oC77%, 2 steps
OTBSO
OOOH
OHO
OAllylO1. iPr2NEt, DMSO, 3h, r.t. then AllylBr, r.t., 1 h, 70%
2. CBr4, PPh3, Et3N, ! 60 oC, 1 h, 89%3. TBAF, 81%
4
6b, Pd(Ph3P)4, Et3N, CuI, r.t. 1 h
then HCO2H, 20 h, 49%
3
1. ClCH2P+Ph3Cl-, nBuLi! 30 oC, 3h
2. tBuOK, DMSO, r.t, 20 min53%, 2 steps
OHO
1. 6a, Pd(Ph3P)4, iPr2NH, CuI, r.t. 1 h, 84%
2. DIBAl, 0 oC, 80%
•
H
HO OH
OH1. MnO2, Et2O, 3h2. Ac2O, pyr, 86%, 2 steps
3. NaBH4, MeOH, 98%4 2
CO2MeI6a
I6b
OH
Sammi Tsegay @ Wipf Group Page 3 of 12 5/23/2010
Katsumra’s Total Synthesis cont.
•
AcO OHO
O
OOH
E/Z 1/3
E/Z > 5/1
Benzener.t. 3 d
50% from aldehyde
NaHMDS
!78 oC dark, 5 min
OOH
OOOHC
•
H
AcO OH
SO2
S
N1. 7, DIAD. PPh3, 78%
2. (NH4)6Mo7O24, aq H2O2, 89%
MnO2
Et2O3
2
HSS
N
7
•
AcO OH
OOH
OO
•
AcO OH
OOH
OO
•
AcO OH
OOH
OO
C33
C35
C39
Katsumura at el Org. Lett. 2009, 11, 5006.
• Peridinin posses large static dipole moment facilitating energy transfer.
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Brückner’s Approach to the Butenolide Moeity:
O
OO
MeO2C
O
OO
MeO2C
4
1
2
EtO2C CO2Et
OH
OH
O
OO
MeO2C
OBu3Sn
OO
MeO2C Br
+
OOHC
41
4-deoxy-4
(!)-diethyl tartrate
• 2 was also prepared in the same fashion.• Later in 2006, used the same methodology to complete the synthesis of Peridinin.
EtO2C CO2Et
O
O
O
O
MeO2C
O
NMe
OMe3 steps 1. NaBH4 (8.0 eqv), 98%
2. Swern [O], 90%O
O
MeO2C3. NaH, THF, 90% E:Z =95:5
P Br
CO2Et
OPhO
PhO
Br
CO2Et
OOHCMeO2C
1. O3, MeOH
2. NaBH43. Sharpless, 67%, 99.8%ee4. Swern [O], 99%
1. LDA, TMSCHN2
2. Bu3SnH, Pd(PPh3)4
OBu3Sn O
OH
MeO2C Br
O
+
1. CuI, Pd2dba3, P(2-furyl)3, 84%2. DEAD, Ph3P, ! 30oC, 52%
1
Amberlyst 15, MeOH reflux, 28 h, 95%
.
Olpp, T.; Brückner, R. Angew. Chem., Int. Ed. 2005, 44, 15533.Olpp, T.; Brückner, R. Angew. Chem., Int. Ed. 2006, 45, 4023.
Sammi Tsegay @ Wipf Group Page 5 of 12 5/23/2010
Burke’s Work: MIDA Mask
B O
N
OO
OO
H B O
N
OO
OOHOHPMBO
B O
N
OO
OOMeOMeOH
1. Me3OBF4, proton sponge, 82%
2. CAN, 77%
1. DMP, 97%
2. CHI3, CrCl2THF:Dioxane, 74%
2
H2N
OMeO OMe
IOMeOMe
B O
N
OO
O
H2N
O
SnBu3
2
3Br
41 Crocacin C
32, Pd(PPh3)4
CuI, CsF, DMFOMeOMe
B O
N
OO
O
H2N
O62%
4, Pd(OAc)2
SPhos, K3PO477%
1
• Highly unreactive.• Very stable to most C-C conditions.• Easily removable under mild conditions.• Stable to silica chromatography and storage.
• 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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Title Paper - Key Reaction:
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.
•Pd2(dba)3, Ligand
THF:H2O, rt, 1.5 h
(R)
PhB(OH)2, Ag2OH
R X
H•
H
R Ph
H
(R)
Key Reaction:
OO
•OHO OAc
HO
OTBSO
B O
N
OOO
B1O
O
BrB O
N
OOOB2
B O
N
OOO
I
B3•
OAc
TMSOH
I
B4
Iterative Cross Coupling (ICC)
Stereoretentive SM cross-coupling
R CH
C CH
Xcat. Pd(PPh3)4
PhZn2 or PhZnClR C
HC C
HPh
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Pd(0)-Catalysed Phenylation of 1-Haloallenes:
PdL4
PdL2
PhZnYZnXY
R CH
C CPd
H
L X
LR CH
C CPd
H
Ph L
L
R CH
C CH
PhR C
HC C
HXInversion:
X•
HR
H PdL2
!PdL2
X•
HR
H
PdL2
SN2'
antiH
RH
PdL2X
H•
PdR
H
X
L
L
[1,3]-shift
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.
(retention)
I•
HR
H Pd•
R
H
H
L
LI
(R) (R)
Pd(PPh3)4halide transfer C
HC C H
PdI ILL
cage
H•
XR
H
(R)
Ph•
HR
H
H•
PhR
H
Inversion
Retention
X = I
X = Cl or Br
Proposed catalytic cycle
Elsevier, C. J.; Vermeer, P. J. Org. Chem. 1985, 50, 3042.
Sammi Tsegay @ Wipf Group Page 8 of 12 5/23/2010
Application in Synthesis:
Lera’s Synthesis of Peridinin:
• X
H
AcO OH
Oxidative addition • PdL2X
H
AcO OH
Transmatalation then Reductive Elimination Product with Retention
"PdL2"
• PdL2X
H
AcO OHHO OHPdL2X
anti-SN2' displacement of Br
superfacial1,3-shift
Transmatalation then Reductive Elimination Product with Inversion
HO OH
1. CuBr, NH4Br HBr, Et2O, 85%
2. Ac2O, pyr, 85%
• Br
H
AcO OH
[Pd(PhCN)2Cl2],
(iPr)2NEt, DMF:THF 64%
Bu3Sn SO2BT•
AcO OH
SO2BT
6'-epi-Peridinin6'
Haloallene Natural Products:
O
OH
H
OMs
H
LiCuBr2
O
OH
HH
•
HBr
H
Panacene
O
OH
H
Br
H
• HBr
H
H
O
Br Br
BrBr
O
H
H
Br
H
OH
Laurellene
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.
Sammi Tsegay @ Wipf Group Page 9 of 12 5/23/2010
Title Paper: Forward Synthesis
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.
OTBSO
OTBSO
B O
N
OO
OB1
pinBH
Cy2BH81%
OTBSO
B O
OHO2C
MeN
CO2H
DMSO, 3 cycles73%
OO
•OHO OAc
HO OTBSO
B O
N
OOO
B1
OO
BrB O
N
OOOB2
B O
N
OOO
I
B3
•
OAc
TMSOH
I
B4
Iterative Cross Coupling (ICC)
Stereoretentive SM cross-coupling
B O
N
OO
O
Bu3SnHMo. cat
THF84%
Bu3SnB O
N
OO
O
OO
BrB O
N
OO
O
1, Pd2(dba)3, Ph3As
THF77% B2
OO
Br Br
1
Structure confirmed by X-rayMo cat = [Mo(allyl)Br(CO)2(CH3CN)2]
Sammi Tsegay @ Wipf Group Page 10 of 12 5/23/2010
Total Synthesis of (-)-Peridinin: Final Steps
Woerly, E. M.; Cherney, A. H.; Davis, E. K.; Burke, M. D. J. Am. Chem. Soc. (ASAP)
B O
N
OO
OIB O
N
OO
O
1. Br2, CH2Cl2
2. DBU, MeCN67%
B O
N
OO
OBr
1. 2, PdCl2(PPh3)2, DMF:THF, 74%
2. I2, MeOH, 77%B O
N
OO
OI
1. 2, Pd(PPh3)4, CuTc, DMF, 58%
2. I2, MeOH, 75%B3
OTBSO
B O
N
OO
O
1. NaOH, THF:H2O, 95%
2. B2, Pd(OAc)2, XPhos, K3PO4, Tol:THF, 79%
OO
OTBSO
B O
N
OO
O
1. pinacol, NaHCO3, MeOH, 99%
2. B3, PdCl2(PPh3)2, Ag2O, DMSO, 45%
OO
OTBSO
B O
N
OO
O
1. B4, Pd(OAc)2, XPhos, NaOH, THF:H2O, 60%
2. HF.pyr, THF, 65%
OO
•OHO OAc
HO
OO
BrB O
N
OOOB2
•
OAc
TMSOH
I
B4
(-)-Peridinin
Et3Ge SnBu32
iPrPCy2
iPr
iPr
= XPhos
Sammi Tsegay @ Wipf Group Page 11 of 12 5/23/2010
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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