Synthesis of Sarain A

Structure of Sarain A

C32H50N2O3

Principal investigatorLarry E. Overman
Publication year2007
Synthesis typeTotal
Number of steps 51 (3 parts)
References
Part 1 of 3
intermediate structure
BH3.Me2S, NaBH4
THF
0 °C to RT, 26 h, 54%
intermediate structure
TBDPSCl, Imidazole
THF
0 °C to RT, 52 h, 82%
intermediate structure
H2, Pd/C
EtOAc
RT, 24 h
intermediate structure + intermediate structure
CH2Cl2
RT, 24 h, 73% (2 steps)
intermediate structure
Part 2 of 3
intermediate structure
TsNHBoc, DEAD, Ph3P
THF
0 °C to RT, 24 h, 88%
intermediate structure
  1. n-BuLi
  2. ClCO2Me
THF
-78 °C to RT, , 92%
intermediate structure
H2, Lindlar Catalyst
PhMe
RT, 3 h, 99%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
TMS2NLi
THF, DME
-78 °C, 4.5 h, 71%
intermediate structure
DMSO
180 °C, 60 min, 69%
intermediate structure
AlMe3
PhMe
RT, 90 min, 91%
intermediate structure
  1. TMS2NLi
  2. AllylBr
THF, DMPU
-78 to -55 °C, 25 h, 92%
intermediate structure
HCl
THF, H2O
RT, 48 h, 98%
intermediate structure
Boc2O, DMAP
MeCN
RT, 15 h, 96%
intermediate structure
i-Bu2AlH
CH2Cl2
-78 °C, 25 min
intermediate structure
NaBH3CN
AcOH
RT, 12 h, 93% (2 steps)
intermediate structure
DMSO
130 °C, 4.5 h
intermediate structure
n-Bu4N+ F-, Ac2O
THF, Et3N
70 °C, 16 h
"R = H or Ac (mixture)"
intermediate structure
K2CO3
MeOH
RT, 12 h, 68% (3 steps)
"R = H or Ac (mixture)"
intermediate structure
i-Bu2AlH
CH2Cl2
-78 °C, 5 h, 87%
intermediate structure
NaOMe
THF
0 °C to RT, 4 h
intermediate structure + intermediate structure
Triphosgene, Et3N
CH2Cl2
0 °C, 45 min, 92% (2 steps)
intermediate structure
  1. O3
  2. NaHCO3
  3. Me2S
CH2Cl2, MeOH
-78 °C to RT, 12 h, 92%
intermediate structure + intermediate structure
THF, Et2O
-78 to -10 °C, 80 min
intermediate structure
Phosgene, DMSO, Et3N
CH2Cl2
-78 °C to RT, 30 min, 83% (2 steps)
See the Swern Oxidation
intermediate structure
Ph3P+CH2O(CH2)2TMS Cl-, TMS2NK
THF
-78 °C to RT, 45 min
See the Wittig Reaction
intermediate structure
HF
MeCN, H2O
91% (2 steps)
intermediate structure
TIPSOTf, Et3N
CH2Cl2
-78 °C to RT, 12 h, 97%
intermediate structure
BCl3, 2,6-Di-tert-butyl-4-methylpyridine
CH2Cl2
RT, 15 h, 85%
intermediate structure
TBSCl, Imidazole
MeCN
RT, 2 h
intermediate structure
NaBH4
MeOH
0 °C, 2 h
intermediate structure
TIPSOTf, Et3N
CH2Cl2
RT, 48 h, 75% (3 steps)
intermediate structure
Na, Naphtalene
DME, THF
-78 °C, , 84%
intermediate structure + intermediate structure
NaBH3CN, AcOH
MeCN
RT, 25 min, 94%
intermediate structure
Grubbs catalyst (1st gen.)
CH2Cl2
Reflux, 8 h
intermediate structure
H2, Pd/C
EtOAc
RT, 6 h, 82% (2 steps)
intermediate structure
HCl
THF, H2O
RT, 6 h, 95%
intermediate structure
  1. TMS2NNa
  2. (4-MeOPh)CH2Cl
DMF
RT, 30 min, 89%
intermediate structure
TASF
DMA
100 °C, 60 min
intermediate structure
KOH
EtOH
90 °C, 12 h, 65% (2 steps)
intermediate structure + intermediate structure
PhH
80 °C, 3 h, 86%
intermediate structure
IBX
DMSO
RT, 105 min, 71%
intermediate structure + intermediate structure
THF
-15 °C, 60 min, 68%
intermediate structure
n-Bu4N+ F-
THF
RT, 105 min, 85%
intermediate structure
TESCl, Imidazole
DMF
0 °C, 15 min, 70%
intermediate structure
K2CO3
MeOH
0 °C to RT, 13 h, 92%
intermediate structure
Dess-Martin Periodinane, NaHCO3
CH2Cl2
0 °C, 90 min
intermediate structure + intermediate structure
TMS2NNa
DME
-78 to 0 °C, 85 min, 76% (2 steps)
See the Wittig Reaction
intermediate structure
Pd(PPh3)4, LiCl
THF
RT, 7 d
See the Stille Coupling
intermediate structure
i-Bu2AlH
PhMe
-78 to 0 °C, 25 min, 64% (2 steps)
intermediate structure
Dess-Martin Periodinane, NaHCO3
CH2Cl2
0 °C, 20 min
intermediate structure
Pyr.HF
CH2Cl2
0 °C, 90 min, 49% (2 steps)
intermediate structure