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

Mohammad Shahidul Islam; Abdullah Saleh Alammari; Assem Barakat; Saeed Alshahrani; Matti Haukka; Abdullah Mohammed Al-Majid

doi:10.3390/molecules26237408

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

Molecules. 2021 Dec 6;26(23):7408. doi: 10.3390/molecules26237408.

Authors

Mohammad Shahidul Islam¹, Abdullah Saleh Alammari¹, Assem Barakat¹, Saeed Alshahrani¹, Matti Haukka², Abdullah Mohammed Al-Majid¹

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Chemistry, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland.

Abstract

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.

Keywords: Friedel−Crafts alkylation; asymmetric catalysis; bis-imidazoline; bis-oxazoline; indoles; thiophene; β-nitroolefins.