Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base

Indazoles represent a privileged scaffold in medicinal chemistry. In the presence of strong base, however, N-protected indazoles are prone to an undesirable ring-opening reaction to liberate o-aminobenzonitriles. By employing unprotected indazoles with a free N-H bond, isomerization is averted because the heterocycle is deprotonated in situ. We herein report functional group-tolerant and robust C-S couplings of bromoindazoles with thiols of varying electronic nature in the presence of lithium bis(trimethylsilyl)amide at elevated temperatures.