Synthesis of Taxol

C47H51NO14
Principal investigator | Robert A. Holton |
---|---|
Publication year | 1994 |
Synthesis type | Total |
Number of steps | 46 (linear) |
References |
Part 1 of 1
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t-BuLi
Hexane(s)
Reflux, 5 h

Ti(Oi-Pr)4,
t-BuOOH
CH2Cl2
RT, 2 h, 98% (2 steps)

TfOH,
BF3.OEt2
CH2Cl2
-80 °C, 22 h, 70%
"93 % yield at 75 % conversion"

TESCl,
DMAP
CH2Cl2, Et3N
RT, 105 min


TBSOTf
Pyr
-23 to 0 °C, 105 min, 94% (3 steps)



Pyr,
Phosgene
CH2Cl2, EtOH
-23 to -10 °C, 60 min, 75% (2 steps)


Red-Al
PhMe
-78 °C to RT, 12 h

Pyr,
Phosgene
PhMe
-78 °C to RT, 60 min, 97% (2 steps)



SmI2
THF
RT, 4 h, 92%


LiTMP
THF
-40 to -10 °C, 50 min, 88%
"Also isolated was the C3-epimer (8% yield)."

Red-Al
PhMe
-78 °C, 90 min, 88%

Pyr,
Phosgene
PhMe
-78 to -23 °C, 30 min, 100%

- O3
- P(OMe)3 , Et3N
CH2Cl2, MeOH
-78 to 0 °C

KMnO4,
KH2PO4
Acetone, H2O, t-BuOH
0 °C, 30 min

CH2N2
Et2O
RT, 93% (3 steps)


2-Methoxypropene,
TsOH
THF
0 °C, 10 min, 100%

PhSH,
KSPh
DMF
86 °C, 3.5 h, 92%

Pyr.TsOH
CH2Cl2, THF
RT, 3 h, 92%

n-Bu4N+ I-,
i-Pr2NEt,
BnOCH2Cl
CH2Cl2
Reflux, 32 h, 92%

- i-Pr2NLi
- TMSCl
Et3N, THF
-78 °C, 25 min, 99%




Pyr,
HF
H2O, MeCN
0 °C, 20 min, 63% (2 steps)

Pyr,
OsO4
Et2O, THF
0 °C, 12 h, 80%

TMSCl,
Et3N
CH2Cl2
-78 °C, 60 min

- i-Pr2NLi
- TsCl
THF
-78 to -35 °C, 3.5 h

Pyr,
HF
H2O, MeCN
0 °C, 15 min, 80% (3 steps)

DBU
PhMe
80 to 110 °C, 80 min, 85%

Ac2O,
DMAP
Pyr
RT, 25 h, 72%

Pyr.HF
MeCN
0 °C, 11 h, 100%

PhLi
THF
-78 °C, 10 min, 85%


(PhSeO)2O,
KOt-Bu
THF
-78 to 0 °C, 80 min


DMAP,
Ac2O
Pyr
RT, 19 h, 100% (3 steps)

TASF
THF
RT, 15 min, 94%


TMS2NLi
THF
-45 to 0 °C, 2 h

Pyr,
HF
H2O, MeCN
0 °C, 60 min, 99% (2 steps)

Pd/C,
H2
1 atm
EtOH
Reflux, 45 min, 94%
