Exploiting the Chiral Ligands of Bis(imidazolinyl)- and Bis(oxazolinyl)thiophenes-Synthesis and Application in Cu-Catalyzed Friedel-Crafts Asymmetric Alkylation.

Five new C2-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1-L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a-c) in excellent optical purity and chemical yield. The utility of these new chiral ligands for Friedel-Crafts asymmetric alkylation was explored. Subsequently, the optimized tridentate ligand L5 and Cu(OTf)2 catalyst (15 mol%) in toluene for 48 h promoted Friedel-Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for the asymmetric induction of the Friedel-Crafts asymmetric alkylation.