Synthesis of Functionalized Indoles with an α‐Stereogenic Ketone Moiety Through an Enantioselective Friedel–Crafts Alkylation with (<i>E</i>)‐1,4‐Diaryl‐2‐butene‐1,4‐diones

Abstract

Abstract Chiral complexes of BINOL‐based ligands with hafnium tert ‐butoxide catalyze the enantioselective Friedel–Crafts alkylation of indoles with ( E )‐1,4‐diaryl‐2‐butene‐1,4‐diones at room temperature, with good yields and ee up to 94%. Hafnium(IV) was found to be a more effective Lewis acid than other frequently used metal ions such as titanium(IV) or zirconium(IV). Unlike the enantioselective Friedel–Crafts alkylation of indoles with α,β‐unsaturated compounds where the stereogenic center is generated in the β‐position to a carbonyl group, the Friedel–Crafts alkylation with 2‐butene‐1,4‐diones described here generates an α‐stereogenic center with respect to one of the carbonyl groups. This can be regarded as an inversion of the normal reactivity pattern or umpolung. The enantioselective Friedel–Crafts alkylation of indoles with ( E )‐4‐oxo‐4‐phenylbutenoates using a zirconium(IV)‐BINOL catalyst is also reported. This reaction takes place regioselectively at the carbon in the β‐position to the ketone carbonyl group, generating an α‐ester stereogenic center.