A Tandem Asymmetric Friedel-Crafts Alkylation/Michael Addition: Synthesis of Novel Ergoline Derivatives

Herein, we report the development of an asymmetric tandem Friedel-Crafts alkylation/Michael addition of 4-substituted indoles with trans-beta-nitrostyrene derivatives. By employing a chiral Zn-II-(bis)oxazoline catalyst we could control the formation of three contiguous chiral centers in one step in 57 %-99 % yield and up to > 99 % ee. This methodology provides easy access to a range of novel C-4-substituted products containing the tricyclic core of the ergoline skeleton and allows for the synthesis of tetracyclic ergoline derivatives with four chiral centers, in high enantioselectivity and as single isolated diastereomers.