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.


Enantioselective sulfa-Michael addition reaction of methyl thioglycolate to chalcones derivatives with sterically encumbered quinine squaramide organocatalyst
HASILCIOĞULLARI, DENİZ; Tanyeli, Cihangir (2018-04-04)
Asymmetric organocatalytic sulfa-Michael reactions give access to enantiomerically enriched sulfur containing adducts that can be used as valuable chiral building blocks. A variety of chalcone derivatives were allowed to react with methyl thioglycolate under optimized conditions, in the presence of a bifunctional quinine derived sterically encumbered squaramide organocatalyst, giving rise to excellent stereoselectivities, up to 99% ee. The designed catalyst system proved to be efficient even at gram scale a...
Enantioselective Michael Addition of Nitroalkanes to Nitroalkenes Catalyzed by Chiral Bifunctional Quinine-Based Squaramides
KANBEROĞLU, Esra; Tanyeli, Cihangir (2016-01-01)
A family of chiral bifunctional acid-/base-type quinine/squaramide organocatalysts is shown to be highly active promoters of the conjugate addition of 1-nitropropane to various trans--nitroalkenes. The cooperation of the quinine and the sterically encumbered squaramide moieties catalyzed the Michael addition reactions at 0 degrees C by using a catalyst loading of only 2mol% to afford the 1,3-dinitro Michael adducts with excellent enantioselectivity and diastereoselectivity (up to 95%ee and syn/anti isomers ...
Asymmetric synthesis of 2,3-dihydrofurans with bifunctional quinine / squaramide organocatalysts
Bozdemir, Merve; Tanyeli, Cihangir; Department of Chemistry (2019)
Organocatalytic asymmetric reactions are efficient and environmentally friendly methods to synthesize products with higher enantioselectivities. Asymmetric domino Michael-SN2 reactions are one of the type of organocatalytic reaction frequently used to form carbon-carbon bonds in the synthesis of the derivatives of dihydrofurans, which are intermediates mainly utilized as precessor materials in the pharmaceutical fields. In this thesis, the reaction occuring between acetylacetone and (Z)-(2-bromo-2-nitroviny...
Planar-Chiral Bis-silanols and Diols as H-Bonding Asymmetric Organocatalysts
BEEMELMANNS, Christine; HUSMANN, Ralph; Whelligan, Daniel K.; Özçubukçu, Salih; BOLM, Carsten (2012-06-01)
The successful development of planar-chiral bis-silanols 3a-d and their application as asymmetric organocatalysts in hetero-Diels-Alder (HDA) reactions is described. All precursors were easily prepared by addition of commerically available silyl electrophiles to a dilithiated [2.2]paracyclophane derivative followed by silane oxidations. The analogous bis-carbinols 7a-c have been prepared by addition of suitable Grignard reagents to bis-methoxycarbonyl derivative 6. Both racemic as well as enantiopure planar...
Enantioselective aza-Henry reaction of t-Boc protected imines and nitroalkanes with bifunctional squaramide organocatalysts
Susam, Zeynep Dilşad; Tanyeli, Cihangir (2017-05-07)
An organocatalytic asymmetric aza-Henry reaction of t-Boc protected imines with nitroalkanes has been established by chiral acid-base type bifunctional Cinchona alkaloid/squaramide organocatalysts. The cooperation of a quinine motif as a base and sterically encumbered squaramide (H-bond donor) enabled mostly complete conversion of a range of reactants into the corresponding aza-Henry products at room temperature with good selectivities (up to 91% ee with 10 mol% catalyst loading).
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.