Synthesis of Taxol

Structure of Taxol

C47H51NO14

Part 1 of 3
intermediate structure
2-Chloroacrylonitrile
PhH
130 °C, 72 h, 85%
intermediate structure
KOH
t-BuOH
65 °C, 3 h, 50%
intermediate structure
TBSCl
CH2Cl2
RT, 60 min, 100%
intermediate structure + intermediate structure
THF
RT, 3 h, 80%
intermediate structure
Part 2 of 3
intermediate structure + intermediate structure
PhB(OH)2, Neopentyl glycol
PhH
RT to Reflux, 48.5 h, 61%
intermediate structure
TBSOTf, 2,6-Lutidine, DMAP
CH2Cl2
0 °C, 4 h, 95%
intermediate structure
LiAlH4
Et2O
0 °C, 60 min, 94%
intermediate structure
Camphorsulfonic acid
MeOH
RT, 60 min, 90%
intermediate structure
TBDPSCl, Imidazole
DMF
RT, 6 h, 92%
intermediate structure
BnBr, KH, n-Bu4N+ I-
Et2O
RT, 2 h, 87%
intermediate structure
LiAlH4
Et2O
RT, 12 h, 80%
intermediate structure
2,2-Dimethoxypropane, Camphorsulfonic acid
CH2Cl2
RT, 7 h, 82%
intermediate structure
n-Pr4N+ RuO4-, NMO
MeCN
RT, 2 h, 95%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
n-BuLi
THF
-78 °C to RT, 30 min, 82%
intermediate structure
VO(acac)2, t-BuOOH
PhH
RT, 12 h, 87%
intermediate structure
LiAlH4
Et2O
RT, 7 h, 76%
intermediate structure
KH, Phosgene
Et2O, HMPA
RT, 2 h, 48%
intermediate structure
n-Bu4N+ F-
THF
RT, 7 h, 80%
intermediate structure
n-Pr4N+ RuO4-, NMO
MeCN, CH2Cl2
RT, 2 h, 82%
intermediate structure
(TiCl3)2.2DME, Zn-Cu
DME
70 °C, 60 min, 23%
intermediate structure + intermediate structure
43%
"Also isolated was the correponding diastereoisomer (43% yield)."
intermediate structure
K2CO3
MeOH
90%
intermediate structure
Ac2O, DMAP
CH2Cl2
RT, 2 h, 95%
intermediate structure
n-Pr4N+ RuO4-, NMO
MeCN
RT, 2 h, 93%
intermediate structure
  1. BH3.THF
  2. H2O2
  3. H2O
THF
0 °C, 2.5 h, 55%
intermediate structure
HCl
MeOH, H2O
RT, 5 h, 80%
intermediate structure
Ac2O, DMAP
CH2Cl2
RT, 30 min, 95%
intermediate structure
H2, Pd/C
EtOAc
RT, 30 min, 97%
intermediate structure
TESCl
Pyr
RT, 12 h, 85%
intermediate structure
K2CO3
MeOH
0 °C, 15 min, 95%
intermediate structure
TMSCl, Pyr
CH2Cl2
0 °C, 15 min, 96%
intermediate structure
Tf2O, i-Pr2NEt
CH2Cl2
RT, 30 min, 70%
intermediate structure
Camphorsulfonic acid
MeOH
10 min
intermediate structure
SiO2
CH2Cl2
4 h, 60% (2 steps)
intermediate structure
Ac2O, DMAP
CH2Cl2
RT, 4 h, 94%
intermediate structure
PhLi
THF
-78 °C, 10 min, 80%
intermediate structure
HCrO3Cl.Pyr, NaOAc, Celite
PhH
Reflux, 60 min, 75%
intermediate structure
NaBH4
MeOH
RT, 5 h, 83%
intermediate structure + intermediate structure
TMS2NNa
THF
0 °C, , 78%
"87 % yield at 90 % conversion."
intermediate structure
Pyr.HF
THF
RT, 90 min, 80%
intermediate structure