1,2 Wagner–Meerwein shift in aza-Nazarov cyclization: Bi(iii)-catalyzed substrate-dependent divergent synthesis of highly substituted pyrroles and indenes

Abstract

The Nazarov reaction and its variants such as aza-Nazarov and iso-Nazarov cyclizations are versatile methods for the synthesis of five-membered ring systems including pyrroles and indenes. The 1,2-Wagner Meerwein shift has been combined in a domino sequence with both Nazarov and aza-Nazarov-like reactions for the synthesis of cyclopentenone and indole derivatives, respectively. However, the same sequence has not been applied for the synthesis of pyrroles, possibly due to the high reactivity of 1-azapentadienyl cation intermediates. In this report, we present the first example of an aza-Nazarov/1,2-Wagner Meerwein shift domino sequence for the synthesis of highly substituted pyrroles. The use of Bi(III) as a mild main group metal catalyst was found to be crucial to control the high reactivity of the intermediate. The substrate demonstrated substituent-dependent divergence in product formation to selectively give indenes through iso-Nazarov cyclization. Detailed mechanistic investigations reveal the electrocyclization nature of the reaction involving a cationic intermediate generated under Lewis acid and/or ‘hidden Brǿnsted acid’ catalysis conditions.