Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigator	Isao Kuwajima
Publication year	1998
Synthesis type	Total
Number of steps	66 (3 parts)
References	J. Am. Chem. Soc. 1998, 120, 12980. J. Am. Chem. Soc. 2000, 122, 3811. J. Org. Chem. 1994, 59, 3165.

Part 1 of 3

intermediate structure

i-Pr2NLi
TESCl

THF

-78 °C, 30 min

intermediate structure

NaHCO3, mCPBA

CH2Cl2

0 °C, 30 min, 96% (2 steps)

See the Rubottom Oxidation

intermediate structure

PhSCHLiOMe

THF

-78 °C, 2 h

intermediate structure

CuO, CuCl2

MeOH, THF

Reflux, 4 h, 54% (2 steps)

intermediate structure

BnOH, TsOH

PhH

Reflux, 6 h

intermediate structure

CSCl2, DMAP

CH2Cl2

0 °C to RT, 30 min, 64% (2 steps)

intermediate structure

Special reagent

2,6-Di-tert-butylphenol

THF

RT, 48 h, 82%

See the Corey-Winter Olefin Synthesis

intermediate structure

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Part 2 of 3

intermediate structure

n-BuLi
EtCOH

THF

-78 to 0 °C, 3 h

intermediate structure

H2, Lindlar Catalyst

1 atm

Hexane(s)

RT, 7 h

intermediate structure

(COCl)2, DMSO, Et3N

CH2Cl2

-78 °C to RT, 10 h

See the Swern Oxidation

intermediate structure

i-Pr2NLi, i-PrCO2Et

THF

-78 to 0 °C, 2.5 h

See the Michael Addition

intermediate structure

KOt-Bu

Et2O

0 °C, 3 h

See the Dieckmann Condensation

intermediate structure

Et3N, t-BuCOCl

CH2Cl2

RT, ON

intermediate structure

TsOH

MeOH

RT, 3 h, 52% (7 steps)

intermediate structure

Et3N, DMSO, (COCl)2

CH2Cl2

-78 to 0 °C, ON, 92%

See the Swern Oxidation

intermediate structure

DBU, DMAP, TIPSOTf

CH2Cl2

-78 °C to RT, 4 h, 71%

intermediate structure

K2CO3, K3Fe(CN)6, K2OsO2(OH)4, DHQ-PHN

t-BuOH

0 °C, 11 h, 98%

See the Sharpless Asymmetric Dihydroxylation

intermediate structure

(CH2NHMe)2

Dean-Stark

PhH

Reflux, 30 min

intermediate structure

TIPSCl, KOMe

Et3N, THF

-23 °C, 6 h, 62% (2 steps)

intermediate structure

(CH2NHMe)2

Dean-Stark

PhH

Reflux, 30 min

intermediate structure

PhSCHLiTMS

THF

-23 to 0 °C, 4 h, 64% (2 steps)

See the Peterson Olefination

intermediate structure

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Part 3 of 3

intermediate structure

+

intermediate structure

t-BuMgCl

THF

-78 °C, 90 min, 68%

See the Grignard Reaction

intermediate structure

(MeBO)3, Pyr

PhH

RT, 30 min, 77%

intermediate structure

TiCl2(Oi-Pr)2

CH2Cl2

-78 to 0 °C, 90 min

See the Mukaiyama Aldol Addition

intermediate structure

Pinacol, DMAP

PhH

RT, 60 min, 59% (2 steps)

intermediate structure

n-BuLi
t-Bu2SiHCl

THF

-78 to 0 °C, 2 h

intermediate structure

i-Bu2AlH

CH2Cl2

-78 °C, 60 min

intermediate structure

TBSOTf, 2,6-Lutidine

CH2Cl2

-23 °C, 30 min, 62% (3 steps)

intermediate structure

Tetraphenylporphyrin, O2

hν

CH2Cl2

RT, 7 h

See the Diels-Alder Reaction

intermediate structure

n-Bu3SnH, AIBN

PhH

Reflux, ON, 80% (2 steps)

intermediate structure

Pd(OH)2, H2

1 atm

EtOH

RT, 4.5 h

intermediate structure

PhCH(OMe)2, Camphorsulfonic acid

CH2Cl2

-23 °C, ON, 79% (2 steps)

intermediate structure

Et2Zn, CH2I2

PhMe

0 °C, 30 min, 66%

See the Simmons-Smith Reaction

intermediate structure

Dess-Martin Periodinane

CH2Cl2

RT, ON, 77%

See the Dess-Martin Oxidation

intermediate structure

H2, Pd(OH)2

1 atm

EtOH

RT, 30 min, 84%

intermediate structure

Pyr, Triphosgene

CH2Cl2

-45 °C, 2 h

intermediate structure

n-Bu4N+ F-

THF

RT, 2.5 h, 95% (2 steps)

intermediate structure

PhCH(OMe)2, Pyr.TsOH

PhH

Reflux, 60 min, 86%

intermediate structure

K2CO3

MeOH, THF

RT, 60 min, 100%

intermediate structure

SmI2

HMPA, THF

RT, 5 h, 100%

intermediate structure

BHT, n-Bu4N+ F-

THF

RT, 3 h

intermediate structure

BHT, NaOMe

MeOH

RT, 60 h, 45% (2 steps)

intermediate structure

PhB(OH)2

CH2Cl2

RT, 15 min

intermediate structure

TBSOTf, 2,6-Lutidine

CH2Cl2

-45 °C, 12 h

intermediate structure

NaHCO3, H2O2

EtOAc, H2O

RT, 60 min, 70% (3 steps)

intermediate structure

Dess-Martin Periodinane

CH2Cl2

RT, 60 min, 92%

See the Dess-Martin Oxidation

intermediate structure

2-Methoxypropene, Pyr.TsOH

CH2Cl2

RT, 5 min, 97%

intermediate structure

TMS2NK
PhNTf2

THF

-78 °C, 60 min, 89%

intermediate structure

TMSCH2MgCl, Pd(PPh3)4

Et2O

RT, 60 min, 91%

See the Kumada-Corriu Coupling

intermediate structure

NCS

MeOH

RT, 10 h, 88%

intermediate structure

i-Pr2NLi
MoOPH

THF

-23 °C, 30 min, 80%

intermediate structure

DMAP, Ac2O

CH2Cl2

RT, 30 min, 92%

intermediate structure

DBN

PhMe

Reflux, 10 h, 71%

intermediate structure

Pyr, OsO4

Et2O

RT, 12 h, 86%

intermediate structure

DBU

PhMe

Reflux, 4 h, 86%

intermediate structure

Pyr.TsOH

MeOH

RT, 30 min

intermediate structure

TESCl, Imidazole, DMAP

DMF

RT, 5 h, 97% (2 steps)

intermediate structure

Pd(OH)2, H2

EtOH

RT, 60 min, 97%

intermediate structure

Triphosgene, Pyr

CH2Cl2

-78 to 0 °C, 60 min, 94%

intermediate structure

DMAP, Ac2O

CH2Cl2

RT, 6 h, 66%

intermediate structure

PhLi

THF

-78 °C, 83%

intermediate structure

Pyr.HF

THF

RT, 2 h, 88%

intermediate structure

ClCO2CH2CCl3, Pyr

CH2Cl2

RT, 3 h, 94%

intermediate structure

TASF

THF

RT, 48 h, 80%

intermediate structure

+

intermediate structure

TMS2NLi

THF

-78 to 0 °C, 30 min, 77%

intermediate structure

Zn

AcOH, H2O

RT, 16 h, 84%

intermediate structure

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