Design and Organocatalytic Asymmetric Synthesis of Indolyl-Pyrroloindoles Bearing Both Axial and Central Chirality

An axially chiral indolyl-pyrroloindole scaffold, a new member of axially chiral indole-based scaffolds, has been designed, and the catalytic asymmetric construction of this scaffold has been established by the strategy of organocatalytic asymmetric (2 + 3) cycloaddition of 3,3 '-bisindoles with isoindolinone-based propargylic alcohols. By this approach, a series of indolylpyrroloindole derivatives bearing both axial chirality and central chirality were synthesized in high yields with excellent diastereoand enantioselectivities (up to 95% yield, 91:9 dr, 99% ee). This reaction not only realizes the first catalytic asymmetric (2 + n) cycloaddition of 3,3 '-bisindoles as 1,2-dinucleophiles but also provides a new strategy for atroposelective construction of axially chiral indole-based scaffolds bearing five-five-membered rings, thus solving the challenges in constructing this class of axially chiral indole-based scaffolds.