Synthesis of Gelsemine

C20H22N2O2
Principal investigator | Larry E. Overman |
---|---|
Publication year | 2005 |
Synthesis type | Total |
Number of steps | 30 (linear) |
References |
Part 1 of 1


SeO2
Dioxane
Reflux, 20 h, 90%


KOH
EtOH, H2O
Reflux, 6 h, 91%


PhOMe,
CF3CO2H
CH2Cl2
RT, 90 min

KCN,
CH2O
THF, Buffer (pH = 7)
RT, 24 h, 81% (2 steps)

n-Bu4N+ F-
THF
-30 °C to RT, 4 h, 95%

- KH , 18-Crown-6
- 2,6-Di-tert-butyl-4-methylpyridine , ClCO2Me
THF
-78 °C to RT, 2.5 h, 81%
See the Cope Rearrangement

Pentamethylpyridine,
Br2
CH2Cl2
-78 °C, 30 min


- TMS2NK
- TESCl
THF
-78 °C to RT, 60 min

PhIO,
BF3.OEt2
CH2Cl2, MeOH
-78 to 0 °C, 3.5 h

- TMS2NK
- Comins' reagent
THF
-78 °C, 30 min, 61% (3 steps)

(dppf)PdCl2,
CO,
n-Bu3N
3.5 atm
DMF, MeOH
80 °C, 18 h, 94%

o-Iodoaniline,
AlMe3
CH2Cl2
-10 °C to RT, 3.5 h, 81%

- NaH
- MeOCH2Cl
THF
RT, 12 h, 86%


HCl
H2O, MeOH
RT, 48 h, 98%

i-Bu3Al
PhMe
-50 °C to RT, 5 h, 71%
"Also isolated was the C3-epimer (12 % yield)."

VinylOEt,
Pyr.TsOH
CH2Cl2
RT, 90 min, 85%

NaCN
DMSO
150 °C, 18 h, 99%

MeOTf
CH2Cl2
0 °C, 15 min

NaCN
DMSO
90 °C, 3 h, 85% (2 steps)

TsOH
CH2Cl2, MeOH
90 °C, 60 min, 99%

DBU
PhMe
110 °C, 9 h, 80%

HCl
DME, H2O
55 °C, 3.5 h

i-Pr2NEt
MeOH
55 °C, 20 h, 90% (2 steps)

i-Bu2AlH
PhMe
0 °C to RT, 3 h

Et3SiH,
CF3CO2H
CH2Cl2
45 °C, 15 h, 65% (2 steps)
