Site-Selective Benzylic Dehydrogenation of Alkylindoles

Benzylic dehydrogenation of alkylarenes represents a crucial transformation in organic synthesis. Notwithstanding the advances reported in this field, achieving precise, tunable site selectivity in the dehydrogenation of molecules with multiple competitive benzylic sites remains an unsolved challenge. Furthermore, achieving this reactivity for dialkylindoles remains elusive. Herein, we report sequential benzylic amination-elimination strategies that allow for the tunably selective benzylic dehydrogenations of alkylindoles at the C2 or C3 position. By employing a commercially available reagent, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) or 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)/pyrazole, 2,3-dialkylindoles can be converted into 2-vinyl-3-alkylindoles or 3-vinyl-2-alkylindoles, respectively, with exceptional site control. Mechanistic studies reveal that C2-benzylic dehydrogenation proceeds via a rare aromatization-driven 1,3-urazole migration, generating a C2-aminated intermediate. Through these strategies, regiodivergent access to different vinylindoles from the same substrates can be facilitated. These protocols are characterized by simple operation, a broad substrate scope, and scalability. Their utility is demonstrated through versatile downstream derivatizations.