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.