Mechanism of a No-Metal-Added Heterocycloisomerization of Alkynylcyclopropylhydrazones: Synthesis of Cycloheptane-Fused Aminopyrroles Facilitated by Copper Salts at Trace Loadings

A mechanistic study
of a new heterocycloisomerization reaction
that forms annulated aminopyrroles is presented. Density functional
theory calculations and kinetic studies suggest the reaction is catalyzed
by trace copper salts and that a Z- to E-hydrazone isomerization occurs through an enehydrazine intermediate
before the rate-determining cyclization of the hydrazone onto the
alkyne group. The aminopyrrole products are obtained in 36–93%
isolated yield depending on the nature of the alkynyl substituent.
A new automated sampling technique was developed to obtain robust
mechanistic data.