Strychnine

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

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Part 1 of 1

ClCO₂CH₂CCl₃

CH₂Cl₂
RT, 40 h, 79 %

Also isolated was the unsaturated ester (10 % yield, see next step).

NaOMe

MeOH
RT, 30 min, 98 %

ClCO₂Me, NaOH, Et₃NBn⁺ Cl^-

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

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

CH₂Cl₂
RT, 3 h

See the Pummerer Rearrangement

HgO, CaCO₃

THF, H₂O
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 %

(EtO)₂P(O)CH₂CN, TMS₂NK

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.