Triple Nucleophilic Head-to-Tail Cascade Polycyclization of Diazodienals via Combination Catalysis: Direct Access to Cyclopentane Fused Aza-Polycycles with Six-Contiguous Stereocenters

Haribabu Chennamsetti; Kuldeep Singh Rathore; Saikat Chatterjee; Pratap Kumar Mandal; Sreenivas Katukojvala

doi:10.1021/jacsau.4c00134

Triple Nucleophilic Head-to-Tail Cascade Polycyclization of Diazodienals via Combination Catalysis: Direct Access to Cyclopentane Fused Aza-Polycycles with Six-Contiguous Stereocenters

JACS Au. 2024 May 24;4(6):2099-2107. doi: 10.1021/jacsau.4c00134. eCollection 2024 Jun 24.

Authors

Haribabu Chennamsetti¹, Kuldeep Singh Rathore¹, Saikat Chatterjee¹, Pratap Kumar Mandal¹, Sreenivas Katukojvala¹

Affiliation

¹ Department of Chemistry, Indian Institute of Science Education & Research Bhopal, Bhopal, Madhya Pradesh 462066, India.

Abstract

Reported herein are the bench stable (2E,4E)-diazohexa-2,4-dienals (diazodienals) and their unprecedented polycyclization with aldimine and arylamines enabled by Rh(II)/Brønsted acid relay catalysis. This scalable and atom-economical reaction provides direct access to the biologically important azatricyclo[6.2.1.0^4,11]undecane fused polycycles having six-contiguous stereocenters. Mechanistic studies revealed that polycyclization proceeds through an unusual triple-nucleophilic cascade initiated by aldimine attack on remote Rh-carbenoid, 6π-electrocyclization of aza-trienyl azomethine ylide, stereoselective aza-Michael addition via iminium activation, and inverse electron-demand intramolecular aza Diels-Alder reaction. The π-π secondary interactions play a crucial role in the preorganization of reactive intermediates for the pericyclic reactions and, hence, the overall efficiency of the polycyclization.