Enantioselektive Synthese von Allyl‐, Propargyl‐ und 4‐En‐2‐inyl‐aminen durch 1,2‐Addition von Organocer‐Reagenzien an chirale Aldimine

Enantioselective Synthesis of Allyl‐, Propargyl‐, and 4‐En‐2‐ynyl‐amines via 1,2‐Addition of Organocerium Reagents to Chiral Aldehyde Imines ( E )‐ and ( Z )‐Allyl‐, propargyl‐, and 4‐en‐2‐ynyl‐amines 5 and 14 , useful bifunctional building blocks and of pharmaceutical interest, are synthesized in high enantiomeric purity (e.e. ≥ 97%). Key step is the diastereoselective 1,2‐addition (d.e. 86 to ≥ 98%) of organocerium reagents to chiral α,β‐unsaturated aldehyde imines 3 or 8 to produce adduct amines 4 and 9 ( Schemes 1 and 4 , resp.). The propargylamine 9 is a substrate for Pd‐catalyzed coupling with alkenyl halides to produce the enynylamine 11a and the thienyl‐substituted alkynylamine 11b . The chiral auxiliary ( S , S )‐ 2 is removed from 4 and 11 in 3 steps affording the title compounds 5 and 14 . Diastereoisomer enrichment of the hydrochloride of 6 by crystallization is possible.