Synthesis of Gelsemine

Structure of Gelsemine

C20H22N2O2

Principal investigatorLarry E. Overman
Publication year2005
Synthesis typeTotal
Number of steps 30 (linear)
References
Part 1 of 1
intermediate structure
Methyl acrylate, AlCl3
CH2Cl2
-78 °C, 7 h, 98%
intermediate structure
SeO2
Dioxane
Reflux, 20 h, 90%
intermediate structure
n-BuLi, Ph3P+CH3 Br-
THF
-78 °C to RT, 3.5 h, 95%
See the Wittig Reaction
intermediate structure
KOH
EtOH, H2O
Reflux, 6 h, 91%
intermediate structure
(PhO)2P(O)N3, (4-MeOPh)CH2OH
Et3N, PhMe
Reflux, 12 h, 72%
intermediate structure
CF3CO2H, PhOMe
CH2Cl2
RT, 90 min
intermediate structure
CH2O, KCN
THF, Buffer (pH = 7)
RT, 24 h, 81% (2 steps)
intermediate structure
n-Bu4N+ F-
THF
-30 °C to RT, 4 h, 95%
intermediate structure
  1. KH
  2. ClCO2Me
  3. 18-Crown-6
  4. 2,6-Di-tert-butyl-4-methylpyridine
THF
-78 °C to RT, 2.5 h, 81%
intermediate structure
Br2, Pentamethylpyridine
CH2Cl2
-78 °C, 30 min
intermediate structure
(CF3CO)2O
CF3CO2H
Reflux, 14 h, 67% (2 steps)
intermediate structure
  1. TMS2NK
  2. TESCl
THF
-78 °C to RT, 60 min
intermediate structure
BF3.OEt2, PhIO
CH2Cl2, MeOH
-78 to 0 °C, 3.5 h
intermediate structure
  1. TMS2NK
  2. Comins' reagent
THF
-78 °C, 30 min, 61% (3 steps)
intermediate structure
n-Bu3N, CO, (DPPF)2PdCl2
DMF, MeOH
80 °C, 18 h, 94%
intermediate structure
AlMe3, o-Iodoaniline
CH2Cl2
-10 °C to RT, 3.5 h, 81%
intermediate structure
  1. MeOCH2Cl
  2. NaH
THF
RT, 12 h, 86%
intermediate structure
Et3N, Pd2(dba)3.CHCl3, Ag3PO4
THF
66 °C, 13 h, 70%
See the Heck Coupling
intermediate structure
HCl
H2O, MeOH
RT, 48 h, 98%
intermediate structure
i-Bu3Al
PhMe
-50 °C to RT, 5 h, 71%
"Also isolated was the C3-epimer (12 % yield)."
intermediate structure
VinylOEt, Pyr.TsOH
CH2Cl2
RT, 90 min, 85%
intermediate structure
NaCN
DMSO
150 °C, 18 h, 99%
intermediate structure
MeOTf
CH2Cl2
0 °C, 15 min
intermediate structure
NaCN
DMSO
90 °C, 3 h, 85% (2 steps)
intermediate structure
TsOH
CH2Cl2, MeOH
90 °C, 60 min, 99%
intermediate structure
DBU
PhMe
110 °C, 9 h, 80%
intermediate structure
HCl
DME, H2O
55 °C, 3.5 h
intermediate structure
i-Pr2NEt
MeOH
55 °C, 20 h, 90% (2 steps)
intermediate structure
i-Bu2AlH
PhMe
0 °C to RT, 3 h
intermediate structure
CF3CO2H, Et3SiH
CH2Cl2
45 °C, 15 h, 65% (2 steps)
intermediate structure