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

J Am Chem Soc. 2017 Aug 2;139(30):10569-10577. doi: 10.1021/jacs.7b06007. Epub 2017 Jul 20.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't