Cascading Auto-oxidative Biproline Guanylations Form Optically Active Dispacamide Dimers and Permit an Eight-Step Synthesis of (−)-Ageliferin

A nickel catalyzed synthesis of isomeric
3,3′-biproline
esters is described. When those materials are doubly acylated with
the acid chloride of pyrrole-2-carboxylic acid, they become susceptible
to auto-oxidation in the presence of guanidine. Through proper staging
of reaction conditions, it is possible to initiate two consecutive
oxidative guanylations prior to in situ cycloisomerization to afford
spirocyclic bis-glycocyamidines. This unique outcome reflects a cascade
of no fewer than 10 reactions occurring sequentially in one flask.
The chemistry provides rapid access to advanced intermediates useful
for the preparation of complex, optically active pyrrole/imidazole
alkaloids.