3-spiroindolizines containing an isoindole ring through intra-molecular arylation of spiro-N-acyliminium species (2019)

Based on N-acyliminium species, efficient approaches to spirocyclic systems connected by two different carbon centers to the isoindole ring have been developed. The imide reduction and the tandem oxidative cleavage of olefin/formyl-amide equilibration were at first selected as the key steps for these strategies. The intramolecular α-amidoalkylation reaction was achieved through the arylation of α-acetoxy lactams or α-hydroxy lactams using, respectively, a Lewis acid or a Brønsted acid depending on the nature of N-acyliminium precursors. All compounds have been characterized by NMR spectroscopy in solution, furthermore the molecular structure of one of this spirocyclic compounds has been elucidated by a single-crystal X-ray diffraction study.
The biological activitiy of these N-heterocyclic compounds on human farnesyltransferase has been investigated.

chemistry, organic (chemistry), biochemistry & molecular biology (fundamental biology)