New enantiopure binaphthyl-cinchona thiosquaramides: synthesis and application for enantioselective organocatalysis

• Published in: New journal of chemistry 2019, Vol.43 (15), p.5948-5959
• Main Authors: Nagy, Sándor, Dargó, Gyula, Kisszékelyi, Péter, Fehér, Zsuzsanna, Simon, András, Barabás, Júlia, Höltzl, Tibor, Mátravölgyi, Béla, Kárpáti, Levente, Drahos, László, Huszthy, Péter, Kupai, József
• Format: Article
• Language: English
• Subjects: Adducts; Catalysis; Catalysts; Chemical synthesis; Conjugates; Enantiomers; Michael reaction; NMR; Nuclear magnetic resonance; Organic chemistry; Quantum chemistry
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/C8NJ06451B

This work presents the first successful applications of cinchona-thiosquaramides in asymmetric reactions. Binaphthyl-cinchona squaramides and thiosquaramides were synthesised, and then used as organocatalysts to promote the catalytic enantioselective Michael addition reaction of pentane-2,4-dione to trans -β-nitrostyrene with excellent yields (up to 99%) and enantioselectivities (up to 99% ee) at as low as 0.2 mol% catalyst loadings. Thiosquaramides gave higher enantioselectivities (up to 92% ee) in conjugate addition reaction of lawsone to β,γ-unsaturated α-keto ester than its oxo analogue, with high yields (up to 100%). Also, only thiosquaramide could catalyse the aza-Diels–Alder addition reaction of 2-siloxydiene to benzylideneacetone. Furthermore, quantum chemical computations showed that the geometrical structure of binaphthyl-cinchona thiosquaramide is similar to that of squaramide.