Internal Nucleophilic Catalyst Mediated Cyclisation/Ring Expansion Cascades for the Synthesis of Medium-Sized Lactones and Lactams

Abstract

A strategy for the synthesis of medium-sized lactones and lactams from linear precursors is described in which an amine acts as an internal nucleophilic catalyst to facilitate a novel cyclisation/ring expansion cascade sequence. This method obviates the need for the high-dilution conditions usually associated with medium-ring cyclisation protocols, as the reactions operate exclusively via kinetically favourable "normal"-sized cyclic transition states. This same feature also enables biaryl-containing medium-sized rings to be prepared with complete atroposelectivity by point-to-axial chirality transfer.

Keywords: atropisomers; axial chirality; medium-sized rings; pyridines; ring expansion.