Synthesis of Doliculide

Structure of Doliculide

C27H41IN2O6

Principal investigator	Arun K. Ghosh
Publication year	2001
Synthesis type	Total
Number of steps	40 (3 parts)
References	Org. Lett. 2001, 3, 635.

Part 1 of 3

intermediate structure

i-Bu2AlH

CH2Cl2

0 °C, 30 min, 85%

intermediate structure

(EtO)2P(O)CH2CO2Et, NaH

THF

0 °C to RT, 4 h, 84%

See the Horner-Wadsworth-Emmons Reaction

intermediate structure

i-Bu2AlH

CH2Cl2

-40 °C, 30 min, 93%

intermediate structure

Special reagent

CH2I2, Et2Zn

CH2Cl2, DME

-15 °C, 8 h, 99%

See the Charette Asymmetric Cyclopropanation

intermediate structure

Ph3P, Imidazole, I2

CH2Cl2

RT, 60 min, 80%

See the Appel Reaction

intermediate structure

(CH2NMe2)2, n-BuLi

4 Å MS

Et2O

-78 °C to RT, 30 min, 90%

intermediate structure

9-BBN
NaOH , H2O2 , H2O

THF

0 °C to RT, 4 h, 80%

intermediate structure

DMSO, (COCl)2, Et3N

CH2Cl2

-78 °C to RT, 2 h

See the Swern Oxidation

intermediate structure

NaH, (EtO)2P(O)CH2CO2Et

THF

0 °C to RT, 4 h, 80% (2 steps)

See the Horner-Wadsworth-Emmons Reaction

intermediate structure

i-Bu2AlH

CH2Cl2

-40 °C, 30 min, 90%

intermediate structure

Special reagent

CH2I2, Et2Zn

CH2Cl2, DME

-15 °C, 8 h, 96%

See the Charette Asymmetric Cyclopropanation

intermediate structure

Ph3P, Imidazole, I2

CH2Cl2

RT, 60 min

See the Appel Reaction

intermediate structure

(CH2NMe2)2, n-BuLi

4 Å MS

Et2O

-78 °C to RT, 30 min, 74% (2 steps)

intermediate structure

O3
Ph3P

CH2Cl2

-78 °C to RT, 4 h

intermediate structure

(EtO)2P(O)CH2CO2Et, NaH

THF

0 °C to RT, 4 h, 60% (2 steps)

See the Horner-Wadsworth-Emmons Reaction

intermediate structure

i-Bu2AlH

CH2Cl2

-40 °C, 30 min, 90%

intermediate structure

(-)-DET, Ti(Oi-Pr)4, t-BuOOH

4 Å MS

CH2Cl2

-23 °C, 20.5 h, 90%

See the Sharpless Epoxidation

intermediate structure

Et3N, DMSO, (COCl)2

CH2Cl2

-78 °C to RT, 2 h

See the Swern Oxidation

intermediate structure

+

intermediate structure

PhH

80 °C, 15 h, 81% (2 steps)

See the Wittig Reaction

intermediate structure

Pd2(dba)3.CHCl3, HCO2H, Et3N, n-Bu3P

Dioxane

RT, 10 h, 90%

intermediate structure

TBSOTf, Et3N

CH2Cl2

0 °C, 15 min

intermediate structure

i-Bu2AlH

CH2Cl2

-40 °C, 30 min, 80% (2 steps)

intermediate structure

t-BuOOH, Ti(Oi-Pr)4, (+)-DET

4 Å MS

CH2Cl2

-23 °C, 20.5 h, 91%

See the Sharpless Asymmetric Dihydroxylation

intermediate structure

MsCl, Et3N, DMAP

CH2Cl2

-78 to 0 °C, 2 h

intermediate structure

NaI

MEK

85 °C, 15 h

See the Finkelstein Reaction

intermediate structure

(CH2NMe2)2, n-BuLi

4 Å MS

Et2O

-78 °C to RT, 30 min, 84% (3 steps)

intermediate structure

Pd/C, H2

1 atm

THF

RT, 6 h, 84%

intermediate structure

n-Pr4N+ RuO4-, NMO

4 Å MS

CH2Cl2

RT, 60 min

See the Ley-Griffith Oxidation

intermediate structure

2-Methyl-2-butene, NaClO2, NaH2PO4

H2O, t-BuOH

RT, ON

See the Pinnick-Lindgren Oxidation

intermediate structure

Boc2O, DMAP

t-BuOH

30 °C, 15 h, 57% (3 steps)

intermediate structure

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Part 2 of 3

intermediate structure

Imidazole, TIPSCl

DMF

0 °C to RT, 2 h, 98%

intermediate structure

MeI, NaH

DMF, THF

60 °C, 20 h

intermediate structure

CF3CO2H

CH2Cl2

0 °C to RT, 3 h, 50% (2 steps)

intermediate structure

+

intermediate structure

HOBt, EDC

DMF

0 °C to RT, 20 h, 90%

intermediate structure

LiOH

H2O, THF

0 °C, 60 min, 100%

intermediate structure

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Part 3 of 3

intermediate structure

+

intermediate structure

DCC, DMAP

CH2Cl2

-20 °C, 20 h, 98%

See the Steglich Esterification

intermediate structure

CF3CO2H

CH2Cl2

0 °C to RT, 3 h

intermediate structure

DMAP, BOP reagent

CH2Cl2

0 °C to RT, 24 h, 82% (2 steps)

intermediate structure

NH3

H2O, MeOH

RT, 60 min, 88%

intermediate structure

n-Bu4N+ F-

THF

0 °C, 15 min, 98%

intermediate structure

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