Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigatorIsao Kuwajima
Publication year1998
Synthesis typeTotal
Number of steps 66 (3 parts)
References
Part 1 of 3
intermediate structure
  1. i-Pr2NLi
  2. TESCl
THF
-78 °C, 30 min
intermediate structure
mCPBA, NaHCO3
CH2Cl2
0 °C, 30 min, 96% (2 steps)
intermediate structure
PhSCHLiOMe
THF
-78 °C, 2 h
intermediate structure
CuO, CuCl2
THF, MeOH
Reflux, 4 h, 54% (2 steps)
intermediate structure
TsOH, BnOH
PhH
Reflux, 6 h
intermediate structure
CSCl2, DMAP
CH2Cl2
0 °C to RT, 30 min, 64% (2 steps)
intermediate structure
2,6-Di-tert-butylphenol
THF
RT, 48 h, 82%
intermediate structure
Part 2 of 3
intermediate structure
  1. n-BuLi
  2. EtCOH
THF
-78 to 0 °C, 3 h
intermediate structure
H2, Lindlar Catalyst
Hexane(s)
RT, 7 h
intermediate structure
DMSO, (COCl)2, Et3N
CH2Cl2
-78 °C to RT, 10 h
See the Swern Oxidation
intermediate structure
i-PrCO2Et, i-Pr2NLi
THF
-78 to 0 °C, 2.5 h
intermediate structure
KOt-Bu
Et2O
0 °C, 3 h
intermediate structure
t-BuCOCl, Et3N
CH2Cl2
RT, ON
intermediate structure
TsOH
MeOH
RT, 3 h, 52% (7 steps)
intermediate structure
DMSO, (COCl)2, Et3N
CH2Cl2
-78 to 0 °C, ON, 92%
See the Swern Oxidation
intermediate structure
TIPSOTf, DBU, DMAP
CH2Cl2
-78 °C to RT, 4 h, 71%
intermediate structure
K2OsO2(OH)4, K3Fe(CN)6, K2CO3, DHQ-PHN
t-BuOH
0 °C, 11 h, 98%
intermediate structure
(CH2NHMe)2
PhH
Reflux, 30 min
intermediate structure
TIPSCl, KOMe
THF, Et3N
-23 °C, 6 h, 62% (2 steps)
intermediate structure
(CH2NHMe)2
PhH
Reflux, 30 min
intermediate structure
PhSCHLiTMS
THF
-23 to 0 °C, 4 h, 64% (2 steps)
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
t-BuMgCl
THF
-78 °C, 90 min, 68%
intermediate structure
(MeBO)3, Pyr
PhH
RT, 30 min, 77%
intermediate structure
TiCl2(Oi-Pr)2
CH2Cl2
-78 to 0 °C, 90 min
intermediate structure
Pinacol, DMAP
PhH
RT, 60 min, 59% (2 steps)
intermediate structure
  1. n-BuLi
  2. 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
O2, Tetraphenylporphyrin
CH2Cl2
RT, 7 h
intermediate structure
n-Bu3SnH, AIBN
PhH
Reflux, ON, 80% (2 steps)
intermediate structure
H2, Pd(OH)2
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%
intermediate structure
Dess-Martin Periodinane
CH2Cl2
RT, ON, 77%
intermediate structure
H2, Pd(OH)2
EtOH
RT, 30 min, 84%
intermediate structure
Triphosgene, Pyr
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
THF, HMPA
RT, 5 h, 100%
intermediate structure
n-Bu4N+ F-, BHT
THF
RT, 3 h
intermediate structure
NaOMe, BHT
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
H2O2, NaHCO3
EtOAc, H2O
RT, 60 min, 70% (3 steps)
intermediate structure
Dess-Martin Periodinane
CH2Cl2
RT, 60 min, 92%
intermediate structure
2-Methoxypropene, Pyr.TsOH
CH2Cl2
RT, 5 min, 97%
intermediate structure
  1. TMS2NK
  2. PhNTf2
THF
-78 °C, 60 min, 89%
intermediate structure
TMSCH2MgCl, Pd(PPh3)4
Et2O
RT, 60 min, 91%
intermediate structure
NCS
MeOH
RT, 10 h, 88%
intermediate structure
  1. i-Pr2NLi
  2. MoOPH
THF
-23 °C, 30 min, 80%
intermediate structure
Ac2O, DMAP
CH2Cl2
RT, 30 min, 92%
intermediate structure
DBN
PhMe
Reflux, 10 h, 71%
intermediate structure
OsO4, Pyr
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
H2, Pd(OH)2
EtOH
RT, 60 min, 97%
intermediate structure
Triphosgene, Pyr
CH2Cl2
-78 to 0 °C, 60 min, 94%
intermediate structure
Ac2O, DMAP
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