Tandem Catalytic Asymmetric Friedel–Crafts/Henry Reaction: Control of Three Contiguous Acyclic Stereocenters

Good things come in threes: Highly functionalized indole derivatives with three contiguous stereocenters were formed in the title reaction of an indole, a nitroalkene, and an aldehyde with the imidazoline–aminophenol catalyst 1–CuOTf in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The major isomers of the adducts were obtained with up to 99 % ee. Tf=trifluoromethanesulfonyl, Ts=p-toluenesulfonyl; R=H, Me; R′,R′′=alkyl, aryl.