Catalytic Enantioselective (4+4) Annulation of o-Hydroxybenzyl Alcohols with 4-Indolylmethanols

A catalytic enantioselective (4+4) annulation of o-hydroxybenzyl alcohols with 4-indolylmethanols has been established under chiral phosphoric acid (CPA) catalysis. By this protocol, a variety of chiral indole-based eight-membered heterocycles are prepared in generally good yields with high enantioselectivities (up to 89% yield, up to 99:1 er). This reaction realizes the first catalytic enantioselective (4+4) annulation of o-hydroxybenzyl alcohols and represents the first catalytic enantioselective (4+4) annulation of 4-indolylmethanols, which will enrich the chemistry of o-hydroxybenzyl alcohols and indolylmethanols. Furthermore, this protocol will offer a new strategy for synthesizing enantioenriched indole-based eight-membered heterocycles.