Synthesis of Taxol

C47H51NO14
Principal investigator | Teruaki Mukaiyama |
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Publication year | 1999 |
Synthesis type | Total |
Number of steps | 61 (linear) |
References |
Part 1 of 1
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H2SO4,
NaNO2
H2O
0 °C to RT, 5.5 d

H2SO4,
HC(OMe)3
MeOH
60 °C, 30 min, 88% (2 steps)

Imidazole,
TBSCl
DMF
0 °C, 6 h, 82%

TfOH,
Cl3C(=NH)OBn
Et2O
RT, 10 h, 100%

i-Bu2AlH
Hexane(s)
-78 °C, 60 min, 95%

i-PrCO2Me,
i-Pr2NLi
Et2O
-78 °C, 65%
See the Aldol Addition
"Also isolated was the C3-epimer (20 % yield)."

Cl3C(=NH)OCH2(p-MeOPh),
TfOH
CH2Cl2
0 °C, 3 h, 75%
"99 % yield based on 76 % conversion."

i-Bu2AlH
Hexane(s)
-78 °C, 60 min, 92%



MgBr2.OEt2
PhMe
-15 °C, 75 min, 71%
See the Mukaiyama Aldol Addition
"87 % yield based on 88 % conversion. Also isolated was the C2-epimer (16 % yield)."

2,6-Lutidine,
TBSOTf
CH2Cl2
0 °C, 60 min, 100%

i-Bu2AlH
PhMe
-78 °C, 60 min




- TMS2NLi
- TMSCl
THF
-78 °C, 90 min

NBS
THF
0 °C, 30 min, 100% (2 steps)

- TMS2NLi
- MeI
HMPA, THF
-78 °C, 2.5 h, 100%

HCl
H2O, THF
0 °C, 60 min, 83%



Ac2O,
DMAP
Pyr
RT, 90 min, 87%

DBU
PhH
60 °C, 90 min, 91%


CuCN,
t-BuLi
Et2O
-78 to 0 °C, 2 h, 92%
See the Michael Addition
"99 % yield base on 93 % conversion."

HCl
H2O, THF
0 °C, 97%



AlH3
PhMe, THF
-78 °C, 2 h, 94%

2,2-Dimethoxypropane,
Camphorsulfonic acid
CH2Cl2
RT, 60 min, 100%

DDQ
CH2Cl2, H2O
RT, 60 min, 97%

H2Cr2O7.2Pyr
CH2Cl2
RT, 16 h, 90%
"94 % yield based on 96 % conversion."

s-BuLi,
4-Iodobutene
Cyclohexane, PhH
-23 to 0 °C, 85 min, 96%

n-Bu4N+ F-
THF
50 °C, 60 min, 100%

Imidazole,
CyMeSiCl2
DMF
RT, 15 min, 99%

MeLi
HMPA, THF
-78 °C, 30 min, 96%





n-Bu4N+ F-
THF
RT, 5 min, 100%

Pyr,
Triphosgene
CH2Cl2
-45 °C, 70 min, 100%

Ac2O,
DMAP
PhH
0 to 35 °C, 10 h, 84%

HCl
H2O, THF
60 °C, 10 h

TESCl
Pyr
0 °C to RT, 40 min, 83% (2 steps)


DMAP,
TCDI
PhMe
100 °C, 8 h


NaOAc,
HCrO3Cl.Pyr,
Celite
PhH
95 °C, 7 h, 78%

K(s-Bu)3BH
THF
-23 °C, 4 h, 87%

TESOTf
Pyr
-23 °C, 10 min, 98%

CuBr,
BzOOt-Bu
Dark
MeCN
-23 to 50 °C, 14 h, 62%
See the Wohl-Ziegler Reaction
"Also isolated was the desired exocyclic allylic bromide (15 % yield, see next step)."

CuBr
MeCN
50 °C, 100 min, 69%
"The yield was 92 % yield brsm."

Pyr,
OsO4
Et2O, THF
RT, 17 h, 92%
"96 % yield based on 96 % conversion."

DBU
PhMe
50 °C, 105 min, 42%
"81 % yield based on 52 % conversion."

Ac2O,
DMAP
Pyr
RT, 13 h, 91%

PhLi
THF
-78 °C, 15 min, 94%

Pyr.HF
THF
RT, 60 min, 96%

TESCl
Pyr
RT, 30 min, 87%
"92 % yield based on 95 % conversion."


DMAP,
DPTC
PhMe
73 °C, 4 h, 66%

H2,
Pd(OH)2/C
1 atm
EtOH
RT, 23 h, 76%

Pyr.HF
THF
RT, 72 h, 100%
