Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigatorRobert A. Holton
Publication year1994
Synthesis typeTotal
Number of steps 46 (linear)
References
Part 1 of 1
intermediate structure
t-BuLi
Hexane(s)
Reflux, 5 h
intermediate structure
t-BuOOH, Ti(Oi-Pr)4
CH2Cl2
RT, 2 h, 98% (2 steps)
intermediate structure
BF3.OEt2, TfOH
CH2Cl2
-80 °C, 22 h, 70%
"93 % yield at 75 % conversion"
intermediate structure
DMAP, TESCl
CH2Cl2, Et3N
RT, 105 min
intermediate structure
t-BuOOH, Ti(Oi-Pr)4
CH2Cl2
0 °C to Reflux, 9.5 h
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
Phosgene, Pyr
CH2Cl2, EtOH
-23 to -10 °C, 60 min, 75% (2 steps)
intermediate structure
i-Pr2NLi
THF
-78 to -35 °C, 70 min, 85%
intermediate structure
Red-Al
PhMe
-78 °C to RT, 12 h
intermediate structure
Phosgene, Pyr
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%
intermediate structure
SmI2
THF
RT, 4 h, 92%
intermediate structure
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
Phosgene, Pyr
PhMe
-78 to -23 °C, 30 min, 100%
intermediate structure
  1. Et3N
  2. O3
  3. P(OMe)3
CH2Cl2, MeOH
-78 to 0 °C
intermediate structure
KH2PO4, KMnO4
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%
intermediate structure
TsOH, 2-Methoxypropene
THF
0 °C, 10 min, 100%
intermediate structure
KSPh, PhSH
DMF
86 °C, 3.5 h, 92%
intermediate structure
Pyr.TsOH
CH2Cl2, THF
RT, 3 h, 92%
intermediate structure
BnOCH2Cl, i-Pr2NEt, n-Bu4N+ I-
CH2Cl2
Reflux, 32 h, 92%
intermediate structure
  1. i-Pr2NLi
  2. TMSCl
Et3N, THF
-78 °C, 25 min, 99%
intermediate structure
mCPBA
Hexane(s)
RT, 5 h, 74%
intermediate structure
MeMgBr
CH2Cl2
-65 to -48 °C, 16.5 h, 95%
intermediate structure
PhMe
Reflux, 20 min
intermediate structure
HF, Pyr
H2O, MeCN
0 °C, 20 min, 63% (2 steps)
intermediate structure
OsO4, Pyr
Et2O, THF
0 °C, 12 h, 80%
intermediate structure
Et3N, TMSCl
CH2Cl2
-78 °C, 60 min
intermediate structure
  1. i-Pr2NLi
  2. TsCl
THF
-78 to -35 °C, 3.5 h
intermediate structure
HF, Pyr
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
NMO, n-Pr4N+ RuO4-
CH2Cl2
RT, 15 min, 100%
intermediate structure
KOt-Bu, (PhSeO)2O
THF
-78 to 0 °C, 80 min
intermediate structure
KOt-Bu
THF
-78 °C, 10 min
intermediate structure
Ac2O, DMAP
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
HF, Pyr
H2O, MeCN
0 °C, 60 min, 99% (2 steps)
intermediate structure
H2, Pd/C
EtOH
Reflux, 45 min, 94%
intermediate structure