Asymmetric Organocatalytic Friedel-Crafts Alkylation-Cyclization Cascade Reaction of Indoles with o-Hydroxyaromatic α,β-Unsaturated Aldehydes

An asymmetric organocatalytic Friedel-Craft alkylation-cyclization cascade reaction of indoles with o-hydroxyaromatic α,β-unsaturated aldehydes was developed to produce chiral 4-substituted chroman-2-ols in moderate to good yields with up to 81:19 er. A variety of chroman derivatives can be readily obtained through the subsequent transformation of these products having the biologically useful molecular scaffolds of indole and chroman. Further study of this reaction's applicability with other substrates to facilitate the preparation of more biologically relevant compounds is underway. The indole molecular scaffold is the most widely distributed heterocycle found in nature. In addition, substituted indoles are important in drug discovery because of their presence in numerous biologically active natural products and their high-affinity binding to many receptors. Func-tionalization of indole rings is therefore an important branch of organic chemistry and various synthetic approaches have been reported. Friedel-Crafts alkylation is one of the most powerful methods for the construction of substituted indole ring especially when applied to catalytic asymmetric transformations. Nowadays, asymmetric organocatalysis has been new paradigm for the catalytic enantioselective Friedel-Crafts alkylation of indoles