8/6/2019 alliacol

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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