Intramolecular Buchwald-Hartwig -arylation of bicyclic hydrazines: practical access to spiro[indoline-2,3′-piperidines]

• Published in: Organic & biomolecular chemistry Vol. 21; no. 17; pp. 3542 - 3546
• Main Authors: Fleurisson, Claire, Graidia, Nessrine, Foricher, Yann, Benedetti, Erica, Micouin, Laurent
• Format: Journal Article
• Published: 03.05.2023
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d3ob00406f

In recent years, spirocycles have been the focus of medicinal chemistry, and several drugs or drug candidates incorporating these "non-planar" chemical motifs have been developed. Herein, an unusual intramolecular Buchwald-Hartwig N -arylation of bicyclic hydrazines is described. This key reaction gives access to various spiro[indoline-2,3′-piperidine] derivatives after reductive cleavage of a nitrogen-nitrogen bond. Following this strategy, unprecedented spiro compounds can be obtained in up to 42% yields over 5 steps. Our approach widens the chemical space of spirocycles and may be useful to explore new avenues of research in drug discovery. An intramolecular Buchwald-Hartwig N -arylation of bicyclic hydrazines and the subsequent reductive cleavage of their N-N bond provide straightforward access to unprecedented spiro[indoline-2,3′-piperidine] derivatives.