Taxol

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C₄₇H₅₁NO₁₄

Author	Paul A. Wender
Publication year	1997
Synthesis type	Formal synthesis
Number of steps	40 (linear)
References	J. Am. Chem. Soc. 1997, 119, 2755. J. Am. Chem. Soc. 1997, 119, 2757.

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Part 1 of 1

KOt-Bu, PrenylBr

DME
-78 °C to RT, 4 h, 41 %

The yield was 82 % brsm.

O₃, Thiourea

CH₂Cl₂, MeOH
5 h, 85 %

hν

MeOH
0 °C, 3 h, 85 %

i-Pr₂NLi, Ethyl propynoate, TMSCl

THF
-78 to 0 °C, 89 %

MeLi, CuI

Et₂O
-78 °C to RT, ON, 97 %

See the Michael Addition
See the Aldol Addition

(Ph₃P)₃RuCl₂, NMO

Acetone
RT, 60 min, 95 %

TMS₂NK

THF
-78 to -20 °C, 2 h, 56 %

97.5 % yield at 57 % conversion.

LiAlH₄

Et₂O
-78 to 0 °C, 2.5 h, 74 %

TBSCl, Imidazole, Pyr^.TsOH, 2-Methoxypropene

CH₂Cl₂
0 °C to RT, 8 h, 91 %

mCPBA, Na₂CO₃

CH₂Cl₂
-78 to -15 °C, 14 h

See the Prilezhaev Reaction

DABCO ®, TIPSOTf, 2,6-Lutidine

CH₂Cl₂
-78 °C to Reflux, 14 h, 85 % (2 steps)

See the Grob Fragmentation

KOt-Bu, O₂, P(OEt)₃

THF
-40 °C, 10 min, 74 %

NaBH₄

MeOH
RT, 90 min, 91 %

H₂
1 atm

CH₂Cl₂
RT, 30 min, 92 %

TMSCl, Triphosgene

Pyr
-78 °C to RT, 2 h, 95 %

HCrO₃Cl^.Pyr
4 Å MS

CH₂Cl₂
RT, 2 h, 100 %

TMS₂NK, Ph₃P⁺CH₂OMe Cl^-

THF
-78 °C to RT, 85 min, 91 %

See the Wittig Reaction

HCl, NaI

Dioxane, H₂O
RT, 18 h, 85 %

94 % yield based on 90 % conversion.

TESCl, Pyr

CH₂Cl₂
-78 to -20 °C, 10 h, 92 %

Dess-Martin Periodinane, NaHCO₃, H₂CN⁺Me₂ I^-

CH₂Cl₂, Et₃N
RT, ON, 97 %

See the Mannich Reaction

AllylMgBr, ZnCl₂

THF
-78 °C, 17 min, 89 %

See the Grignard Reaction

BnOCH₂Cl, i-Pr₂NEt
Sealed tube

CH₂Cl₂
60 °C, 72 h

NH₄F

MeOH
RT, 12 h, 93 % (2 steps)

PhLi, Ac₂O, DMAP

THF, Pyr
-78 °C to RT, 2.5 h, 79 %

CH₂Cl₂
80 min, 50 %

See the Lobry-de Bruyn-van Ekenstein Rearrangement
80 % yield based on 63 % conversion.

O₃, P(OEt)₃

CH₂Cl₂
-78 °C to RT, 86 %

ClCO₂CH₂CCl₃, DMAP

CH₂Cl₂
RT, 42 h, 62 %

See the Aldol Addition

HCl, NaI

Acetone, H₂O
RT, 21 h, 65 %

97 % yield based on 67 % conversion.

MsCl, DMAP

CH₂Cl₂, Pyr
0 °C, 3 h, 83 %

LiBr

Acetone
RT, 72 h, 73 %

See the Finkelstein Reaction
79 % yield based on 94 % conversion.

OsO₄, Pyr

THF
RT, 23 h, 71 %

76 % yield based on 94 % conversion.

Triphosgene, Pyr

CH₂Cl₂
0 °C, 30 min, 92 %

KCN

EtOH
0 °C, 3 h, 68 %

76 % yield based on 89 % conversion.

i-Pr₂NEt

PhMe
Reflux, 9 h, 79 %

95 % yield based on 83 % conversion.

Ac₂O, DMAP

CH₂Cl₂
RT, ON, 89 %

TASF

THF
0 °C, 5 min, 96 %

PhLi

THF
-78 °C to RT, 15 min, 58 %

Also isolated was the C10-alcohol (30 % yield) which can be acetylated to the desired product.

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Remaining...

54 % (3 steps)

See : Chem. Eur. J. 1999, 5, 121; Nature 1994, 367, 630.