(3+2)-Annulation of 1,3-N,Si-tetraorganosilane reagents (TsHNCH2SiBnRR2)-R-1 with arynes for efficient synthesis of 3-silaindolines

1,3-N,Si-Tetraorganosilane reagents (TsHNCH2SiBnRR2)-R-1 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 (TsHNCH2SiBnRR2)-R-1 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.