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

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.