Abstract
The enantioselective transformations of indoles preferentially take place in the more-reactive azole ring. However, the methods for the enantioselective functionalization of the indole benzene ring are scarce. In this paper, a series of bifunctional (thio)urea derivatives were used to organocatalyze the enantioselective Friedel-Crafts hydroxyalkylation of indoles with isatins. The resulting products were obtained in good yields (65–90%) with up to 94% enantiomer excess (ee). The catalyst type and the substrate scope were broadened in this methodology.
Highlights
The indole scaffolds are privileged skeletons, as they have been widely found in many bioactive natural products, pharmaceuticals, and material molecules [1,2,3,4,5,6]
In summary, we described how the first urea derivative catalyst promoted the enantioselective hydroxyalkylation of hydroxyindoles with isatins
The enantioselective modification happened in the benzene ring rather than in the azole ring to give the desired hydroxyalkylated indoles with high enantioselectivity
Summary
The indole scaffolds are privileged skeletons, as they have been widely found in many bioactive natural products, pharmaceuticals, and material molecules [1,2,3,4,5,6]. Indoles show a high nucleophilic reactivity in the azole ring, which preferentially reacts with electrophilic aromatic substitution at the C-3 position [15,16,17,18,19,20,21,22] These Friedel-Crafts (F-C) reactions selectively take place at the positions C-2 [23,24,25,26,27,28,29,30] and N-1 [31,32,33,34,35,36,37] by using different strategies. The functionalization in the benzene ring of indole is still difficult, which generally requires the presence of directing or blocking group in the azole ring [38,39,40,41,42,43,44,45,46] and employs transition metal catalysts [47,48,49]
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