Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigator	Robert A. Holton
Publication year	1994
Synthesis type	Total
Number of steps	46 (linear)
References	J. Am. Chem. Soc. 1994, 116, 1597. J. Am. Chem. Soc. 1994, 116, 1599. J. Am. Chem. Soc. 1988, 110, 6558.

Part 1 of 1

intermediate structure

t-BuLi

Hexane(s)

Reflux, 5 h

intermediate structure

Ti(Oi-Pr)4, t-BuOOH

CH2Cl2

RT, 2 h, 98% (2 steps)

intermediate structure

TfOH, BF3.OEt2

CH2Cl2

-80 °C, 22 h, 70%

"93 % yield at 75 % conversion"

intermediate structure

TESCl, DMAP

CH2Cl2, Et3N

RT, 105 min

intermediate structure

Ti(Oi-Pr)4, t-BuOOH

CH2Cl2

0 °C to Reflux, 9.5 h

See the Grob Fragmentation

intermediate structure

TBSOTf

Pyr

-23 to 0 °C, 105 min, 94% (3 steps)

intermediate structure

+

intermediate structure

i-Pr2NMgBr

THF

-23 °C to RT, 2.5 h

See the Aldol Addition

intermediate structure

Pyr, Phosgene

CH2Cl2, EtOH

-23 to -10 °C, 60 min, 75% (2 steps)

intermediate structure

Special reagent

i-Pr2NLi

THF

-78 to -35 °C, 70 min, 85%

See the Davis Asymmetric Hydroxylation

intermediate structure

Red-Al

PhMe

-78 °C to RT, 12 h

intermediate structure

Pyr, Phosgene

PhMe

-78 °C to RT, 60 min, 97% (2 steps)

intermediate structure

(COCl)2, DMSO, Et3N

CH2Cl2

-78 °C to RT, 30 min, 95%

See the Swern Oxidation

intermediate structure

LiTMP

THF

-23 to -10 °C, 30 min, 90%

See the Chan Rearrangement

intermediate structure

SmI2

THF

RT, 4 h, 92%

intermediate structure

Special reagent

LiTMP

THF

-40 to -10 °C, 50 min, 88%

"Also isolated was the C3-epimer (8% yield)."

intermediate structure

Red-Al

PhMe

-78 °C, 90 min, 88%

intermediate structure

Pyr, Phosgene

PhMe

-78 to -23 °C, 30 min, 100%

intermediate structure

O3
P(OMe)3 , Et3N

CH2Cl2, MeOH

-78 to 0 °C

intermediate structure

KMnO4, KH2PO4

Acetone, H2O, t-BuOH

0 °C, 30 min

intermediate structure

CH2N2

Et2O

RT, 93% (3 steps)

intermediate structure

i-Pr2NLi

THF

-78 °C, 40 min, 84%

See the Dieckmann Condensation

intermediate structure

2-Methoxypropene, TsOH

THF

0 °C, 10 min, 100%

intermediate structure

PhSH, KSPh

DMF

86 °C, 3.5 h, 92%

intermediate structure

Pyr.TsOH

CH2Cl2, THF

RT, 3 h, 92%

intermediate structure

n-Bu4N+ I-, i-Pr2NEt, BnOCH2Cl

CH2Cl2

Reflux, 32 h, 92%

intermediate structure

i-Pr2NLi
TMSCl

Et3N, THF

-78 °C, 25 min, 99%

intermediate structure

mCPBA

Hexane(s)

RT, 5 h, 74%

See the Rubottom Oxidation

intermediate structure

MeMgBr

CH2Cl2

-65 to -48 °C, 16.5 h, 95%

See the Grignard Reaction

intermediate structure

Special reagent

PhMe

Reflux, 20 min

See the Burgess Dehydration

intermediate structure

Pyr, HF

H2O, MeCN

0 °C, 20 min, 63% (2 steps)

intermediate structure

Pyr, OsO4

Et2O, THF

0 °C, 12 h, 80%

intermediate structure

TMSCl, Et3N

CH2Cl2

-78 °C, 60 min

intermediate structure

i-Pr2NLi
TsCl

THF

-78 to -35 °C, 3.5 h

intermediate structure

Pyr, HF

H2O, MeCN

0 °C, 15 min, 80% (3 steps)

intermediate structure

DBU

PhMe

80 to 110 °C, 80 min, 85%

intermediate structure

Ac2O, DMAP

Pyr

RT, 25 h, 72%

intermediate structure

Pyr.HF

MeCN

0 °C, 11 h, 100%

intermediate structure

PhLi

THF

-78 °C, 10 min, 85%

intermediate structure

n-Pr4N+ RuO4-, NMO

CH2Cl2

RT, 15 min, 100%

See the Ley-Griffith Oxidation

intermediate structure

(PhSeO)2O, KOt-Bu

THF

-78 to 0 °C, 80 min

intermediate structure

KOt-Bu

THF

-78 °C, 10 min

See the Lobry-de Bruyn-van Ekenstein Rearrangement

intermediate structure

DMAP, Ac2O

Pyr

RT, 19 h, 100% (3 steps)

intermediate structure

TASF

THF

RT, 15 min, 94%

intermediate structure

+

intermediate structure

TMS2NLi

THF

-45 to 0 °C, 2 h

intermediate structure

Pyr, HF

H2O, MeCN

0 °C, 60 min, 99% (2 steps)

intermediate structure

Pd/C, H2

1 atm

EtOH

Reflux, 45 min, 94%

intermediate structure

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