Application of a One-Pot Friedel-Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

Herein, we report a short and facile stereoselective route to ergoline derivatives. The key steps are a one-pot Friedel-Crafts alkylation/Michael addition sequence which, in the absence of chiral ligands, affords the trans-trans-stereoisomer in 44% yield as a racemate. Screening of a range of chiral bisoxazoline ligands allowed this sequence to proceed in 42-55% yields (six examples), with up to 99% ee. This approach allows for the first time, substitution at the C-4-position and the introduction of 3 chiral centres in one pot. An interesting, base-mediated conversion of the trans-trans-stereoisomer to the cis-cis-stereoisomer was discovered and both stereoisomers were characterized by X-ray crystallography.