Synthesis of Indoles Using the Electrophilic Potential of Diazirines

The electrophilic potential of diazirines has been utilized to obtain N-substituted diaziridines that are directly hydrolyzed to produce monosubstituted hydrazines. The hydrazines can undergo the Fisher process with enolizable carbonyls to yield multiple indole derivatives in moderate to high yields. The N-metalated diaziridine intermediates can undergo isomerization prior to electrophilic substitution, to form N,N-disubstituted hydrazones. The latter react with enolizable carbonyls to produce N-protected indole derivatives in a single step. This protocol was used to efficiently synthesize indomethacin, an anti-inflammatory drug.