Enantioselective sulfa-michael addition to trans-chalcone derivatives with quinine derived bifunctional organocatalysts

Tözendemir, Deniz
The use of organocatalysts has brought profound advantages in the context of asymmetric synthesis, in terms of ease of use and better compatibility with the environment. More than 20 organocatalysts of four different classes (squaramide, urea, thiourea, and sulfonamide) have been developed and used to catalyze various asymmetric reactions in our research group. In this thesis, asymmetric sulfa-Michael type additions were carried out in the presence of cinchona alkaloid derived squaramide and sulfonamide-type organocatalysts of our design. The first part of the thesis focuses on sulfa-Michael addition of methyl thioglycolate to trans-chalcones. 23 enantiomerically enriched chalcone derivatives (>99% yield, 68-99% ee) and 4 enantiomerically enriched aryl butenone derivatives (31-71% yield, 61-77% ee) were synthesized in the presence of a squaramide/quinine type organocatalyst. A nitro-substitued sulfa-Michael adduct was selected for further reactions which yielded optically and biologically active 1,4-benzothiazepin-2-one derivative. In the second part of the study, 1-naphthalenethiol was added to trans-chalcones in the similar fashion, in the presence of a sulfonamide/quinine type bifunctional organocatalyst. A total of 15 enantiomerically enriched sulfa-Michael adducts (β-aryl-β-sulfanyl ketones) containing thionaphthol moiety were synthesized with moderate to excellent enantioselectivities (51-96% ee). Selected β-aryl-β-sulfanyl ketones were oxidized to obtain corresponding optically active sulfones.
Citation Formats
D. Tözendemir, “Enantioselective sulfa-michael addition to trans-chalcone derivatives with quinine derived bifunctional organocatalysts,” Ph.D. - Doctoral Program, Middle East Technical University, 2020.