Cu(ii)-thiophene-2,5-bis(amino-alcohol) mediated asymmetric Aldol reaction and Domino Knoevenagel Michael cyclization: a new highly efficient Lewis acid catalyst.

The highly efficient Lewis acid-catalytic system Cu(ii)-thiophene-2,5-bis(amino-alcohol) has been developed for enantioselective Aldol reaction of isatin derivatives with ketones. The new catalytic system also proved to be highly enantioselective for the one pot three-component Domino Knoevenagel Michael cyclization reaction of substituted isatin with malononitrile and ethylacetoacetate. The chiral ligand (2,2')-2,2'-((thiophene-2,5-diylbis(methylene))bis(azanediyl))bis(3-phenylpropan-1-ol) (L1) in combination with Cu(OAc)·HO employed as a new Lewis acid catalyst, furnished 3-substituted-3-hydroxyindolin-2-ones derivatives (3a-s) in good to excellent yields (81-99%) with high enantioselectivities (up to 96% ee) and spiro[4-pyran-3,3-oxindole] derivatives (6a-l) in excellent yields (89-99%) with high ee (up to 95%).

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

Five new -symmetric chiral ligands of 2,5-(imidazolinyl)thiophene () and 2,5-(oxazolinyl)thiophene ( and ) were synthesized from thiophene-2,5-dicarboxylic acid () with enantiopure amino alcohols (-) 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 and Cu(OTf) 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% ).