alliacol
TRANSCRIPT
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O
O
OH
O
1. Alliacol A
OTBSO
TBSO
Anodic Cyclization Reaction:
The Total Synthesis of Alliacol A
Mihelcic, J.; Moeller, K. D. J. Am. Chem. Soc. 2003, 125, 36
OTBSO
TBSO
Anodic Oxidation
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Anode(Oxidation) Cathode(Reduction)
eA
A
R
R
Workingelectrode Auxiliary
electrodeAnode m teri ls: C rbonorPl tium
Solvents: MeOH,AcOH, CH3CN, CH2Cl2Electrolytes: Et4NOTs, LiClO4, Bu4NBF4
transfer
net
Syst m f B si El tr l ysis ti
Fu m t l I t rm i t s
R R R
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Synt ti ppli ti ns f nodi El tr ochemistry
Elimination & Fragmentation Reactions
Coupling Reactions: Trap the initial reactive intermediates
generatedat theanode
Reactions that generateractivereagents
Advantage
Selectively oxidizing functional groups
Generating highly reactive intermediates
Reversing the pol rit yofnucleophiles
Typical Anodic Reactions
Moeller, . . Tetrahedron2000, 56, 9527
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Eli ination & rag entation Reactions
OH
O
O
OR
anode
-H
RCO2H
R
N
CO2H
COR1
R2CO2H+anode
N
R2
COR1
Carboxylic Acids
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R
N
O
RN
O
RN
O
RN
O
anode
-H -e
-eMeOH
RN
O
MeO
N
OMeO
N
OMeO
N
OMeO
Nuanode
-2e, -H
A ides
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NMeO CO2Me
N
OH
CO2Me
OH
H
NMeO CO2Me
N
OH
CO2Me
OH
H
NMeO CO2Me
N
OH
CO2Me
OH
H
N
MeO CO2Me
N
OH
CO2Me
OH
H
N
MeO CO2Me
N
OH
CO2Me
OH
H
OMe
N
MeO CO2Me
N
OH
CO2Me
OH
H
OMe
N
MeO CO2Me
N
CO2Me
OH
H
OMeO
A ines
anode
-e -H
-e
H MeOH
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Intr molecul r nodicOlefin oupling
Nu-H
X
Nu-H
X
Nu
X
Nu
X
Yanode -H
-e
-e
solvent
(HY)
O
n
n = 1,2
O
n
n = 1,2
OMe
Ptanode
MeOH/ Bu4NBF4
OC6H1OH
OC6H1
O
Ptanode
LiBF4
NaOEt/EtOH
Ethers nd lcohols
CouplingReactions
54%
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Intra olec lar Aryl lefin Co ling
OMe
OH
OMe
OAc
OMe
OH
OMe
OAc
OMe
O
OMe
OAc
OO
MeO
OAc
OO
MeO
OAc
anode
-e
-H, -e
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O
MeO
O
MeO
MeO OMe
O
MeO OMe
RVCanode
LiClO4MeOH/ CH2Cl2
2,6-lutidine
2 /mol
OTMSO OOH H O
O
O
O
X
R1
R2
X
R1
R2
X OMeR2
R1
OMeR2
R1
anode
Intra olec lar Aryl lefin Co ling
anode
6 %
%
CyathinCore
-e, -H-e
Wright, D. L.; Whitehead, C. R.; Sessions, E. H.; Ghi righ, I.; rey, D. A. Org. Lett. 1999, 1, 1535.
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O
O
OH
O
1. Alliacol A
O
HO
MeO
O
HO
HO
OTBSO
TBSO
OTBSO
TBSO
2 3
45
SyntheticPlan
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O
OH
O
OTBS
P(OEt)2
O
OTBSO
TBSO
56 7
OTBSO
O
OO
H
MeO
O
HO
HO
3
O
HO
MeO2
1. Br2, MeOH0 to 8 C
2. TBSCl
3. P(OEt)3, 130 C 2%
1. NaH, THF;
2. Me2Cu(CN)Li2 TBSCl, THF 1%
RVCanodecarbon catode0.4 M LiClO4MeOH/CH2Cl2
(1:4)2,6-lutidine,RT15-20 mA
TsOH, RT
1. I2, PPh3,imidazole
2. AgNO3,
THF/MeOH(2:1) RT, 3.5h
88%
80%
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O
HO
MeO2
O
H
10
HO
O O
11
OH
1. IBAL
OO2.
1. LiEt3BH, THF, 3%2. TsCl, Py, 3%3. BU, MF, 73%
O
O
OH
O
1. Alliacol A
O OH
O
O OH
O
O
mCPBA
RuCl3nH2O
NaIO4
LiTMP;Eschemmoser'ssalt
Ref. J. Or . hem1995, 60, 4822