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

12 February 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Reported herein are the bench stable (2E,4E)-diazohexa-2,4-dienals (diazodienals) and their unprecedented polycy-clization 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[,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, 6-electrocyclization of aza-trienyl azomethine ylide, stereoselective aza-Michael addition via iminium activation and inverse electron-demand intramolecular aza Diels-Alder reaction. The secondary interactions play a crucial role in the preorganization of reactive intermediates for the pericyclic reactions and hence the overall efficiency of the polycyclization.




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