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 C4‐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. In a short and stereoselective route to ergoline derivatives the key steps are a one‐pot Friedel–Crafts alkylation/Michael addition sequence. Screening of a range of chiral bisoxazoline ligands allowed this sequence to proceed in up to 55 % yield (six examples), with up to 99 % ee. This approach allows substitution at the C4‐position and the introduction of three chiral centres.