Chiral N,N'-Dioxide-Scandium(III) Complex-Catalyzed Asymmetric Friedel-Crafts Alkylation Reaction of ortho-Hydroxybenzyl Alcohols with C3-Substituted N-Protected Indoles

Abstract

The first Lewis acid catalyzed asymmetric Friedel-Crafts alkylation reaction of ortho-hydroxybenzyl alcohols with C3-substituted indoles is described. A chiral N,N'-dioxide Sc(OTf)₃ complex served not only to promote formation of ortho-quinone methides (o-QMs) in situ but also induced the asymmetry of the reaction. This methodology enables a novel activation of ortho-hydroxybenzyl alcohols, thus affording the desired chiral diarylindol-2-ylmethanes in up to 99 % yield and 99 % ee. A range of functional groups were also tolerated under the mild reaction conditions. Moreover, this strategy gives concise access to enantioenriched indole-fused benzoxocines.

Keywords: Friedel-Crafts alkylation; asymmetric catalysis; diarylindol-2-ylmethanes; indole; ortho-quinone methides.