(3 + 2)-Annulation of 1,3-N,Si-tetraorganosilane reagents TsHNCH2SiBnR1R2 with arynes for efficient synthesis of 3-silaindolines

Abstract

1,3-N,Si-Tetraorganosilane reagents TsHNCH₂SiBnR¹R² were developed as robust synthons to prepare 3-silaindolines via a Cs₂CO₃-promoted (3 + 2)-annulation reaction with arynes. The annulation involved a chemoselective Si–C bond cleavage/formation sequence, where the Si–Bn bond in TsHNCH₂SiBnR¹R² and the Si–Ar bond in aryl silyl triflates were cleaved, and a new Si–Ar bond together with a N–Ar bond was formed. The nitrogen and aryl moieties in the products could be further functionalized to expand the structural diversity of 3-silaindolines. The approach allowed the development of a 3-silaindoline-containing CB₂ agonist, which showed a higher CNS penetration and better antinociceptive effect than its carbon analog.