Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigatorTeruaki Mukaiyama
Publication year1999
Synthesis typeTotal
Number of steps 61 (linear)
References
Part 1 of 1
intermediate structure
NaNO2, H2SO4
H2O
0 °C to RT, 5.5 d
intermediate structure
HC(OMe)3, H2SO4
MeOH
60 °C, 30 min, 88% (2 steps)
intermediate structure
TBSCl, Imidazole
DMF
0 °C, 6 h, 82%
intermediate structure
Cl3C(=NH)OBn, TfOH
Et2O
RT, 10 h, 100%
intermediate structure
i-Bu2AlH
Hexane(s)
-78 °C, 60 min, 95%
intermediate structure
i-PrCO2Me, i-Pr2NLi
Et2O
-78 °C, , 65%
See the Aldol Addition
"Also isolated was the C3-epimer (20 % yield)."
intermediate structure
Cl3C(=NH)OCH2(p-MeOPh), TfOH
CH2Cl2
0 °C, 3 h, 75%
"99 % yield based on 76 % conversion."
intermediate structure
i-Bu2AlH
Hexane(s)
-78 °C, 60 min, 92%
intermediate structure
DMSO, (COCl)2, Et3N
CH2Cl2
-78 °C to RT, 75 min, 97%
See the Swern Oxidation
intermediate structure + intermediate structure
MgBr2.OEt2
PhMe
-15 °C, 75 min, 71%
"87 % yield based on 88 % conversion. Also isolated was the C2-epimer (16 % yield)."
intermediate structure
TBSOTf, 2,6-Lutidine
CH2Cl2
0 °C, 60 min, 100%
intermediate structure
i-Bu2AlH
PhMe
-78 °C, 60 min
intermediate structure
DMSO, (COCl)2, Et3N
CH2Cl2
-78 °C to RT, 75 min, 94% (2 steps)
See the Swern Oxidation
intermediate structure
MeMgBr
Et2O
-78 °C, 100 min, 99%
intermediate structure
DMSO, (COCl)2, Et3N
CH2Cl2
-78 °C to RT, 45 min, 97%
See the Swern Oxidation
intermediate structure
  1. TMS2NLi
  2. TMSCl
THF
-78 °C, 90 min
intermediate structure
NBS
THF
0 °C, 30 min, 100% (2 steps)
intermediate structure
  1. TMS2NLi
  2. MeI
THF, HMPA
-78 °C, 2.5 h, 100%
intermediate structure
HCl
THF, H2O
0 °C, 60 min, 83%
intermediate structure
DMSO, (COCl)2, Et3N
CH2Cl2
-78 °C to RT, 75 min, 95%
See the Swern Oxidation
intermediate structure
SmI2
THF
-78 °C, 20 min, 70%
intermediate structure
Ac2O, DMAP
Pyr
RT, 90 min, 87%
intermediate structure
DBU
PhH
60 °C, 90 min, 91%
intermediate structure + intermediate structure
t-BuLi, CuCN
Et2O
-78 to 0 °C, 2 h, 92%
"99 % yield base on 93 % conversion."
intermediate structure
HCl
THF, H2O
0 °C, , 97%
intermediate structure
n-Pr4N+ RuO4-, NMO
CH2Cl2
0 °C, 30 min, 92%
intermediate structure
NaOMe
MeOH, THF
0 °C, , 90%
See the Aldol Addition
"Also isolated was the C4-epimer (8 % yield)."
intermediate structure
AlH3
PhMe, THF
-78 °C, 2 h, 94%
intermediate structure
2,2-Dimethoxypropane, Camphorsulfonic acid
CH2Cl2
RT, 60 min, 100%
intermediate structure
DDQ
CH2Cl2, H2O
RT, 60 min, 97%
intermediate structure
H2Cr2O7.2Pyr
CH2Cl2
RT, 16 h, 90%
"94 % yield based on 96 % conversion."
intermediate structure
4-Iodobutene, s-BuLi
Cyclohexane, PhH
-23 to 0 °C, 85 min, 96%
intermediate structure
n-Bu4N+ F-
THF
50 °C, 60 min, 100%
intermediate structure
CyMeSiCl2, Imidazole
DMF
RT, 15 min, 99%
intermediate structure
MeLi
THF, HMPA
-78 °C, 30 min, 96%
intermediate structure
n-Pr4N+ RuO4-, NMO
CH2Cl2, MeCN
0 °C to RT, 60 min, 80%
intermediate structure
PdCl2
DMF, H2O
RT, 3.5 h, 98%
intermediate structure
TiCl2, LiAlH4
THF
0 °C to Reflux, 40 min, 43-71%
intermediate structure
Na
NH3, THF
-78 to -45 °C, 2 h, 100%
See the Birch Reduction
intermediate structure
n-Bu4N+ F-
THF
RT, 5 min, 100%
intermediate structure
Triphosgene, Pyr
CH2Cl2
-45 °C, 70 min, 100%
intermediate structure
Ac2O, DMAP
PhH
0 to 35 °C, 10 h, 84%
intermediate structure
HCl
THF, H2O
60 °C, 10 h
intermediate structure
TESCl
Pyr
0 °C to RT, 40 min, 83% (2 steps)
intermediate structure
n-Pr4N+ RuO4-, NMO
CH2Cl2
RT, 60 min, 76%
intermediate structure
TCDI, DMAP
PhMe
100 °C, 8 h
intermediate structure
P(OMe)3
110 °C, 5 h, 53% (2 steps)
intermediate structure
HCrO3Cl.Pyr, NaOAc, Celite
PhH
95 °C, 7 h, 78%
intermediate structure
K(s-Bu)3BH
THF
-23 °C, 4 h, 87%
intermediate structure
TESOTf
Pyr
-23 °C, 10 min, 98%
intermediate structure
CuBr, BzOOt-Bu
MeCN
-23 to 50 °C, 14 h, 62%
"Also isolated was the desired exocyclic allylic bromide (15 % yield, see next step)."
intermediate structure
CuBr
MeCN
50 °C, 100 min, 69%
"The yield was 92 % yield brsm."
intermediate structure
OsO4, Pyr
Et2O, THF
RT, 17 h, 92%
"96 % yield based on 96 % conversion."
intermediate structure
DBU
PhMe
50 °C, 105 min, 42%
"81 % yield based on 52 % conversion."
intermediate structure
Ac2O, DMAP
Pyr
RT, 13 h, 91%
intermediate structure
PhLi
THF
-78 °C, 15 min, 94%
intermediate structure
Pyr.HF
THF
RT, 60 min, 96%
intermediate structure
TESCl
Pyr
RT, 30 min, 87%
"92 % yield based on 95 % conversion."
intermediate structure + intermediate structure
DPTC, DMAP
PhMe
73 °C, 4 h, 66%
intermediate structure
H2, Pd(OH)2/C
EtOH
RT, 23 h, 76%
intermediate structure
Pyr.HF
THF
RT, 72 h, 100%
intermediate structure