Cinchona‐Based Hydrogen‐Bond Donor Organocatalyst Metal Complexes: Asymmetric Catalysis and Structure Determination
Dr. Sándor Nagy,
Dóra Richter,
Gyula Dargó,
Balázs Orbán,
Gergő Gémes,
Dr. Tibor Höltzl,
Zsófia Garádi,
Zsuzsanna Fehér,
Dr. József Kupai
Affiliations
Dr. Sándor Nagy
Department of Organic Chemistry and Technology Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Dóra Richter
Department of Organic Chemistry and Technology Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Gyula Dargó
Department of Organic Chemistry and Technology Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Balázs Orbán
ELKH-BME Computation Driven Chemistry Research Group Department of Inorganic and Analytical Chemistry Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Gergő Gémes
Department of Organic Chemistry and Technology Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Dr. Tibor Höltzl
ELKH-BME Computation Driven Chemistry Research Group Department of Inorganic and Analytical Chemistry Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Zsófia Garádi
Department of Pharmacognosy Semmelweis University Üllői út. 26 1085 Budapes Hungary
Zsuzsanna Fehér
Department of Organic Chemistry and Technology Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Dr. József Kupai
Department of Organic Chemistry and Technology Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary
Abstract In this study, we describe the synthesis of cinchona (thio)squaramide and a novel cinchona thiourea organocatalyst. These catalysts were employed in pharmaceutically relevant catalytic asymmetric reactions, such as Michael, Friedel–Crafts, and A3 coupling reactions, in combination with Ag(I), Cu(II), and Ni(II) salts. We identified several organocatalyst‐metal salt combinations that led to a significant increase in both yield and enantioselectivity. To gain insight into the active catalyst species, we prepared organocatalyst‐metal complexes and characterized them using HRMS, NMR spectroscopy, and quantum chemical calculations (B3LYP‐D4/def2‐TZVP), which allowed us to establish a structure‐activity relationship.
