Synthesis of Taxol

C47H51NO14
Principal investigator | Isao Kuwajima |
---|---|
Publication year | 1998 |
Synthesis type | Total |
Number of steps | 66 (3 parts) |
References |
Part 1 of 3

- i-Pr2NLi
- TESCl
THF
-78 °C, 30 min


PhSCHLiOMe
THF
-78 °C, 2 h

CuO,
CuCl2
MeOH, THF
Reflux, 4 h, 54% (2 steps)

BnOH,
TsOH
PhH
Reflux, 6 h

CSCl2,
DMAP
CH2Cl2
0 °C to RT, 30 min, 64% (2 steps)


Part 2 of 3

- n-BuLi
- EtCOH
THF
-78 to 0 °C, 3 h

H2,
Lindlar Catalyst
1 atm
Hexane(s)
RT, 7 h




Et3N,
t-BuCOCl
CH2Cl2
RT, ON

TsOH
MeOH
RT, 3 h, 52% (7 steps)


DBU,
DMAP,
TIPSOTf
CH2Cl2
-78 °C to RT, 4 h, 71%

K2CO3,
K3Fe(CN)6,
K2OsO2(OH)4,
DHQ-PHN
t-BuOH
0 °C, 11 h, 98%

(CH2NHMe)2
Dean-Stark
PhH
Reflux, 30 min

TIPSCl,
KOMe
Et3N, THF
-23 °C, 6 h, 62% (2 steps)

(CH2NHMe)2
Dean-Stark
PhH
Reflux, 30 min


Part 3 of 3
+
+



(MeBO)3,
Pyr
PhH
RT, 30 min, 77%


Pinacol,
DMAP
PhH
RT, 60 min, 59% (2 steps)

- n-BuLi
- t-Bu2SiHCl
THF
-78 to 0 °C, 2 h

i-Bu2AlH
CH2Cl2
-78 °C, 60 min

TBSOTf,
2,6-Lutidine
CH2Cl2
-23 °C, 30 min, 62% (3 steps)


n-Bu3SnH,
AIBN
PhH
Reflux, ON, 80% (2 steps)

Pd(OH)2,
H2
1 atm
EtOH
RT, 4.5 h

PhCH(OMe)2,
Camphorsulfonic acid
CH2Cl2
-23 °C, ON, 79% (2 steps)



H2,
Pd(OH)2
1 atm
EtOH
RT, 30 min, 84%

Pyr,
Triphosgene
CH2Cl2
-45 °C, 2 h

n-Bu4N+ F-
THF
RT, 2.5 h, 95% (2 steps)

PhCH(OMe)2,
Pyr.TsOH
PhH
Reflux, 60 min, 86%

K2CO3
MeOH, THF
RT, 60 min, 100%

SmI2
HMPA, THF
RT, 5 h, 100%

BHT,
n-Bu4N+ F-
THF
RT, 3 h

BHT,
NaOMe
MeOH
RT, 60 h, 45% (2 steps)

PhB(OH)2
CH2Cl2
RT, 15 min

TBSOTf,
2,6-Lutidine
CH2Cl2
-45 °C, 12 h

NaHCO3,
H2O2
EtOAc, H2O
RT, 60 min, 70% (3 steps)


2-Methoxypropene,
Pyr.TsOH
CH2Cl2
RT, 5 min, 97%

- TMS2NK
- PhNTf2
THF
-78 °C, 60 min, 89%


NCS
MeOH
RT, 10 h, 88%

- i-Pr2NLi
- MoOPH
THF
-23 °C, 30 min, 80%

DMAP,
Ac2O
CH2Cl2
RT, 30 min, 92%

DBN
PhMe
Reflux, 10 h, 71%

Pyr,
OsO4
Et2O
RT, 12 h, 86%

DBU
PhMe
Reflux, 4 h, 86%

Pyr.TsOH
MeOH
RT, 30 min

TESCl,
Imidazole,
DMAP
DMF
RT, 5 h, 97% (2 steps)

Pd(OH)2,
H2
EtOH
RT, 60 min, 97%

Triphosgene,
Pyr
CH2Cl2
-78 to 0 °C, 60 min, 94%

DMAP,
Ac2O
CH2Cl2
RT, 6 h, 66%

PhLi
THF
-78 °C, 83%

Pyr.HF
THF
RT, 2 h, 88%

ClCO2CH2CCl3,
Pyr
CH2Cl2
RT, 3 h, 94%

TASF
THF
RT, 48 h, 80%


TMS2NLi
THF
-78 to 0 °C, 30 min, 77%

Zn
AcOH, H2O
RT, 16 h, 84%
