Synthesis of Doliculide

Structure of Doliculide

C27H41IN2O6

Principal investigatorArun K. Ghosh
Publication year2001
Synthesis typeTotal
Number of steps 40 (3 parts)
References
Part 1 of 3
intermediate structure
i-Bu2AlH
CH2Cl2
0 °C, 30 min, 85%
intermediate structure
(EtO)2P(O)CH2CO2Et, NaH
THF
0 °C to RT, 4 h, 84%
intermediate structure
i-Bu2AlH
CH2Cl2
-40 °C, 30 min, 93%
intermediate structure
Et2Zn, CH2I2
CH2Cl2, DME
-15 °C, 8 h, 99%
intermediate structure
Ph3P, I2, Imidazole
CH2Cl2
RT, 60 min, 80%
See the Appel Reaction
intermediate structure
n-BuLi, (CH2NMe2)2
Et2O
-78 °C to RT, 30 min, 90%
intermediate structure
  1. 9-BBN
  2. H2O2
  3. NaOH
  4. H2O
THF
0 °C to RT, 4 h, 80%
intermediate structure
(COCl)2, DMSO, Et3N
CH2Cl2
-78 °C to RT, 2 h
See the Swern Oxidation
intermediate structure
(EtO)2P(O)CH2CO2Et, NaH
THF
0 °C to RT, 4 h, 80% (2 steps)
intermediate structure
i-Bu2AlH
CH2Cl2
-40 °C, 30 min, 90%
intermediate structure
Et2Zn, CH2I2
CH2Cl2, DME
-15 °C, 8 h, 96%
intermediate structure
Ph3P, I2, Imidazole
CH2Cl2
RT, 60 min
See the Appel Reaction
intermediate structure
n-BuLi, (CH2NMe2)2
Et2O
-78 °C to RT, 30 min, 74% (2 steps)
intermediate structure
  1. O3
  2. Ph3P
CH2Cl2
-78 °C to RT, 4 h
intermediate structure
(EtO)2P(O)CH2CO2Et, NaH
THF
0 °C to RT, 4 h, 60% (2 steps)
intermediate structure
i-Bu2AlH
CH2Cl2
-40 °C, 30 min, 90%
intermediate structure
Ti(Oi-Pr)4, (-)-DET, t-BuOOH
CH2Cl2
-23 °C, 20.5 h, 90%
intermediate structure
(COCl)2, DMSO, Et3N
CH2Cl2
-78 °C to RT, 2 h
See the Swern Oxidation
intermediate structure + intermediate structure
PhH
80 °C, 15 h, 81% (2 steps)
See the Wittig Reaction
intermediate structure
Pd2(dba)3.CHCl3, n-Bu3P, HCO2H, Et3N
Dioxane
RT, 10 h, 90%
intermediate structure
TBSOTf, Et3N
CH2Cl2
0 °C, 15 min
intermediate structure
i-Bu2AlH
CH2Cl2
-40 °C, 30 min, 80% (2 steps)
intermediate structure
Ti(Oi-Pr)4, (+)-DET, t-BuOOH
CH2Cl2
-23 °C, 20.5 h, 91%
intermediate structure
MsCl, Et3N, DMAP
CH2Cl2
-78 to 0 °C, 2 h
intermediate structure
NaI
MEK
85 °C, 15 h
intermediate structure
n-BuLi, (CH2NMe2)2
Et2O
-78 °C to RT, 30 min, 84% (3 steps)
intermediate structure
H2, Pd/C
THF
RT, 6 h, 84%
intermediate structure
n-Pr4N+ RuO4-, NMO
CH2Cl2
RT, 60 min
intermediate structure
NaClO2, 2-Methyl-2-butene, NaH2PO4
t-BuOH, H2O
RT, ON
intermediate structure
Boc2O, DMAP
t-BuOH
30 °C, 15 h, 57% (3 steps)
intermediate structure
Part 2 of 3
intermediate structure
TIPSCl, Imidazole
DMF
0 °C to RT, 2 h, 98%
intermediate structure
NaH, MeI
DMF, THF
60 °C, 20 h
intermediate structure
CF3CO2H
CH2Cl2
0 °C to RT, 3 h, 50% (2 steps)
intermediate structure + intermediate structure
EDC, HOBt
DMF
0 °C to RT, 20 h, 90%
intermediate structure
LiOH
THF, H2O
0 °C, 60 min, 100%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
DCC, DMAP
CH2Cl2
-20 °C, 20 h, 98%
intermediate structure
CF3CO2H
CH2Cl2
0 °C to RT, 3 h
intermediate structure
BOP reagent, DMAP
CH2Cl2
0 °C to RT, 24 h, 82% (2 steps)
intermediate structure
NH3
MeOH, H2O
RT, 60 min, 88%
intermediate structure
n-Bu4N+ F-
THF
0 °C, 15 min, 98%
intermediate structure