Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigator	Samuel J. Danishefsky
Publication year	1996
Synthesis type	Formal
Number of steps	52 (2 parts)
References	J. Am. Chem. Soc. 1996, 118, 2843.

Part 1 of 2

intermediate structure

Et3N, NH2NH2

EtOH

RT, 90 min, 72%

intermediate structure

DBN, I2

THF

RT, 45 min, 52%

See the Barton Vinyl Iodide Synthesis

intermediate structure

DBN, I2

THF

0 °C to RT, 8.5 h, 89%

intermediate structure

KCN, 18-Crown-6, TMSCN

CH2Cl2

0 °C to RT, 8 h, 89%

intermediate structure

Report an error in this part

Part 2 of 2

intermediate structure

NaBH4

EtOH

0 °C, 97%

intermediate structure

DMAP, Ac2O

CH2Cl2, Pyr

0 °C, 99%

intermediate structure

Naphthalenesulfonic Acid, (CH2OH)2

Dean-Stark

PhH

Reflux, 70%

intermediate structure

NaOMe

MeOH, THF

98%

intermediate structure

TBSOTf, 2,6-Lutidine

CH2Cl2

0 °C, 97%

intermediate structure

NaOH, H2O2, BH3.THF

H2O, THF

0 °C to RT, 17 h

intermediate structure

H2Cr2O7.2Pyr

4 Å MS

CH2Cl2

0 °C to RT, 10.5 h

intermediate structure

NaOMe

MeOH

RT, 10 h, 62% (3 steps)

intermediate structure

Me3S+ I-, TMS2NK

THF

0 °C, 2.5 h, 99%

See the Johnson-Corey-Chaykovsky Reaction

intermediate structure

Al(Oi-Pr)3

PhMe

Reflux, 38 h, 99%

intermediate structure

OsO4, NMO

Acetone, H2O, i-PrOH

RT, 15 h, 66%

See the Upjohn Dihydroxylation

intermediate structure

Pyr, Tf2O, TMSCl

CH2Cl2, Ethylene Glycol

-78 °C to Reflux, 69%

intermediate structure

BnBr, NaH, n-Bu4N+ I-

THF

0 °C to RT, 4.5 h, 98%

See the Williamson Ether Synthesis

intermediate structure

TsOH

Acetone, H2O

Reflux, 2.5 h, 84%

intermediate structure

TMSOTf, Et3N

CH2Cl2

-78 °C, 4 h

intermediate structure

DMDO

CH2Cl2

0 °C, 10 min

intermediate structure

Camphorsulfonic acid

Acetone

RT, 30 min, 89% (3 steps)

See the Rubottom Oxidation

intermediate structure

Pb(OAc)4

MeOH, PhH

0 °C, 10 min, 97%

See the Criegee Reaction

intermediate structure

CTPS

MeOH

Reflux, 10 h, 97%

intermediate structure

LiAlH4

THF

0 °C, 60 min, 100%

intermediate structure

o-NO2PhSeCN, n-Bu3P

THF

RT, 15 min, 88%

intermediate structure

H2O2

THF

RT, 12 h, 90%

See the Grieco Dehydration

intermediate structure

O3
Ph3P

CH2Cl2

-78 °C, 79%

intermediate structure

+

intermediate structure

t-BuLi

THF

-78 °C, 55 min, 93%

intermediate structure

n-Bu4N+ F-

THF

-78 °C, 15 min, 80%

intermediate structure

NaHCO3, mCPBA

CH2Cl2

RT, 11 h, 80%

See the Prilezhaev Reaction

intermediate structure

Pd/C, H2

1 atm

EtOH

-5 °C, 65%

intermediate structure

CDI, NaH

DMF

RT, 20 min, 81%

intermediate structure

Li(s-Bu)3BH

THF

-78 °C, 75 min, 93%

intermediate structure

TMS2NK
PhNTf2

THF

-78 °C, 10 min, 98%

intermediate structure

Pyr.TsOH

Acetone, H2O

75 °C, 9 h, 96%

intermediate structure

Ph3P=CH2

THF

-78 to 0 °C, 25 min, 77%

See the Wittig Reaction

intermediate structure

Pd(PPh3)4, K2CO3

MeCN

90 °C, 46%

See the Mizoroki-Heck Reaction

intermediate structure

n-Bu4N+ F-

THF

RT, 8 h, 92%

intermediate structure

TESOTf, Et3N

CH2Cl2

-78 °C, 30 min, 92%

intermediate structure

mCPBA, NaHCO3

CH2Cl2

RT, 10.5 h, 45%

See the Prilezhaev Reaction

intermediate structure

H2, Pd/C

1 atm

EtOH

RT, 10 h, 82%

intermediate structure

DMAP, Ac2O

Pyr

RT, 16 h, 66%

intermediate structure

PhLi

THF

-78 °C, 2 min, 93%

intermediate structure

OsO4

Pyr

105 °C, 24 h

intermediate structure

Pb(OAc)4

MeOH, PhH

0 °C, 5 min, 61% (2 steps)

See the Criegee Reaction

intermediate structure

SmI2, Ac2O

THF

-78 °C, 10 min, 92%

intermediate structure

(PhSeO)2O, KOt-Bu

THF

-78 to 0 °C, 90 min

intermediate structure

KOt-Bu

THF

-78 °C, 10 min, 81% (2 steps)

See the Lobry-de Bruyn-van Ekenstein Rearrangement

intermediate structure

DMAP, Ac2O

Pyr

RT, 16 h, 76%

intermediate structure

HCrO3Cl.Pyr, NaOAc

PhH

Reflux, 60 min, 64%

intermediate structure

NaBH4

MeOH

RT, 2 h, 79%

intermediate structure

Report an error in this part

Remaining...

63% (2 steps)

"See : Nature 1994, 367, 630."

intermediate structure