Formation of N-Alkylpyrroles via Intermolecular Redox Amination

Abstract

Redox isomerization reactions are of particular interest because they exhibit perfect atom economy, and they often utilize the inherent reducing power of hydrogen that is embedded in molecules to effect reduction of other functional groups.1–3 In doing so, redox isomerizations are able to circumvent the requirement for exogenous reducing agents, which tend to be high energy reagents. The power of redox isomerizations is arguably increased when it is used in conjunction with C–X bond-forming reactions. The Tishchenko reaction is a classic example of such a coupling reaction that has been proposed to proceed via an intermediate redox isomerization. 2 More recently, Seidel has demonstrated several intriguing reactions where an intramolecular redox reaction is used to effect a reductive amination in concert with a second C–N bond forming reaction (eq 1).3 Herein, we report a related, acid-catalyzed intermolecular redox amination that takes advantage of the inherent reducing power of 3-pyrroline (eq 2). Ultimately, redox isomerization can be used to form N-alkyl pyrroles via reductive amination, a reaction that cannot typically occur since pyrrole is a weak N-nucleophile. Moreover, the mild conditions, atom-economy, and operational simplicity of the redox amination reported herein make redox amination a viable alternative to more standard syntheses of N-alkyl pyyroles.4