Grob-Type Fragmentation Releases Paracyclophane Ring Strain in a Late-Stage Precursor of Haouamine A

A ketene [2 + 2]-addition, an intramolecular aldol reaction, a Suzuki–Miyaura coupling, and a chemoselective lactam reduction were used to prepare a late-stage precursor of haouamine A. Exposure to acid led to a Grob-type fragmentation of the strained 3-aza[7]­paracyclophane ring, followed by a tandem Pictet–Spengler reaction of the intermediate iminium ion and conversion to a novel 1,4a-propanocyclopenta­[b]­pyridine. This cascade reaction might also be relevant for the mechanism of action of the natural product.