Synthesis of Strychnine

C21H22N2O2

Principal investigator	Philip Magnus
Publication year	1992
Synthesis type	Total
Number of steps	28 (linear)
References	J. Am. Chem. Soc. 1992, 114, 4403. J. Am. Chem. Soc. 1993, 115, 8116.

Part 1 of 1

ClCO2CH2CCl3

CH2Cl2

RT, 40 h, 79%

"The starting material was made according to: Can. J. Chem. 1964, 42, 489. Also isolated was the unsaturated ester (10 % yield, see next step)."

NaOMe

MeOH

RT, 30 min, 98%

Et3NBn+ Cl-, ClCO2Me, NaOH

CH2Cl2, H2O

0 °C, 5 h, 86%

See the Schotten-Baumann Reaction

AcOH, THF

RT, 10 h, 82%

PhSCH2CO2H, BOP-Cl, Et3N

CH2Cl2

0 °C, 95 min, 71%

mCPBA, NaHCO3

CH2Cl2

0 °C, 30 min, 95%

NaH

THF

0 °C, 105 min, 98%

See the Michael Addition

2,6-Di-tert-butyl-4-methylpyridine, (CF3CO)2O

CH2Cl2

RT, 3 h

See the Pummerer Rearrangement

HgO, CaCO3

H2O, THF

RT, 12 h

Br(CH2)2OH, DBU

PhMe

RT, 60 min, 81% (3 steps)

BH3.THF

THF

RT, 60 min, 100%

NaHCO3

MeOH

Reflux, 16 h

Hg(OAc)2

AcOH

RT, 60 h, 43% (2 steps)

Zn, H2SO4

MeOH

Reflux, 30 min, 88%

NaOMe

MeOH

Reflux, 2 h, 100%

4-Methoxybenzenesulfonyl chloride, i-Pr2NEt, DMAP

CH2Cl2

0 °C to RT, 24 h, 81%

LiBH4

THF

50 °C, 19 h, 67%

HClO4

RT, 24 h, 55%

"This product can be obtained from the degradation of natural strychnine and serves as an enantiopure relay."

TIPSOTf, DBU

CH2Cl2

0 °C to RT, 30 min, 69%

TMS2NK, 																	
																						(EtO)2P(O)CH2CN

																	THF															

								RT, 								42 h, 								43%
							
								See the Horner-Wadsworth-Emmons Reaction
							
								"Also isolated was the Z-isomer (29 % yield) which could be photoisomerized to the desired E-isomer."