Synthesis of Thiazoline-Oxazoline Ligands and Their Application in Asymmetric Catalysis

A series of novel ligands incorporating oxazoline and thiazoline units were synthesized in high yield by employing a convergent route, in which the key step is a microwave-assisted palladium-catalyzed aryl amination. The new ligands were tested in the zinc-catalyzed FriedelCrafts alkylation of indole with trans-beta-nitrostyrene, inducing enantiomeric excess values of up to 69?%. The complete series of these ligands was also applied to the chromium-catalyzed NozakiHiyamaKishi (NHK) allylation of benzaldehyde, affording enantiomeric excess values of up to 85?%. A crystal structure of the most successful ligand in this transformation bound to iron(III) was obtained and demonstrated a tridentate binding mode of the ligand. A transition state is proposed to account for the preferential formation of the (R)-enantiomer in the NHK reaction.