The Overman synthesis (1993) took a chiral cyclopentene compound as starting material obtained by enzymatic hydrolysis of cis-1,4-diacetoxycyclopent-2-ene. This starting material was converted in several steps to trialkylstannane 2 which was then coupled with an aryl iodide 1 in a Stille reaction in presence of carbon monoxide (tris(dibenzylideneacetone)dipalladium(0), triphenylarsine). The internal double in 3 was converted to an epoxide using tert-Butyl hydroperoxide, the carbonyl group was then converted to an alkene in a Wittig reaction using PhP=CH and the TIPS group was hydrolyzed (TBAF) and replaced by a trifluoroacetamide group (NHCOCF, NaH) in 4. Cyclization (NaH) took place next, opening the epoxide ring and the trifluoroacetyl group was removed using KOH affording azabicyclooctane 5.
The key step was an aza-Cope-Mannich reaction initiated by an amine-carbonyl condensation using formaldehyde and forming 6 in a quantitative yield:
In the final sequence strychnine was obtained through the Wieland-Gumlich aldehyde (10):
Intermediate 6 was acylated using methyl cyanoformate and two protective groups (tert-butyl and ) were removed using HCl / MeOH in 7. The C8C13 double bond was reduced with zinc (MeOH/H) to saturated ester 8 (mixture). Epimerization at C13 with sodium methoxide in MeOH produced beta-ester 9 which was reduced with diisobutylaluminium hydride to Wieland-Gumlich aldehyde 10. Conversion of this compound with malonic acid to (−)-strychnine 11 was already known as a procedure.