Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

Abstract

SummaryFor the first time, chiral sulfoximine derivatives have been applied as asymmetric organocatalysts. In combination with a thiourea-type backbone the sulfonimidoyl moiety leads to organocatalysts showing good reactivity in the catalytic desymmetrization of a cyclic meso-anhydride and moderate enantioselectivity in the catalytic asymmetric Biginelli reaction. Straightforward synthetic routes provide the newly designed thiourea-sulfoximine catalysts in high overall yields without affecting the stereohomogeneity of the sulfur-containing core fragment.

Functionalized S-perfluorinated sulfoximines: Preparation and evaluation in catalytic processes

“…This one-pot three-component reaction between the benzaldehyde, the b-ketoester 14 and the urea 16, using a thiourea as organocatalyst, was carried out for the synthesis of 3,4-dihydropyrimidin-2(1H)-one 17. The results obtained with sulfoximine thioureas 7a-b were close to the literature (respectively 49% and 65% compared to 42 and 92% yields) [4]. This demonstrated the proper activation of the thiourea by the trifluoromethyl group.…”

“…We were then intrigued by the possibility of the synthesis of ''sulfoximines-thioureas'', previously described by Bolm et al with non perfluorinated sulfoximines [4]. The reaction between the molecule 1a and phenyl isothiocyanate 5a delivered the expected compound 6a albeit with low yield, due to the tamed nucleophilicity of the nitrogen atom induced by the presence of the trifluoromethyl group of the sulfur (VI) moiety (Scheme 3).…”

“…Following the same approach than during the catalytic studies, we started a comparison between thioureas 7a and 7b with their non-fluorinated analogs in a Biginelli's reaction (Scheme 7) [4]. This one-pot three-component reaction between the benzaldehyde, the b-ketoester 14 and the urea 16, using a thiourea as organocatalyst, was carried out for the synthesis of 3,4-dihydropyrimidin-2(1H)-one 17.…”

“…Sulfoximines were also plentifully employed as ligands in catalytic reactions or in enantioselective metal catalysis [3], but surprisingly much more rarely for organocatalytic transformations. [4] The S-perfluoroalkylated sulfoximines have recently grown in importance and revealed very particular properties. They were described as building blocks for liquid crystals [5], as very powerful electron-withdrawing substituents and especially as nucleophilic and electrophilic perfluoroalkylating reagents [6].…”

Exploration of Novel Chemical Space: Synthesis and in vitro Evaluation of N‐Functionalized Tertiary Sulfonimidamides

“…Phenyl[oxo(phenyl)(piperidin-1-yl)-l 6 N-Aminocarbonylation of sulfonimidamide 2aa(urea formation): General procedure E [52] To as olution of sulfonimidamide 2aa (100 mg, 0.45 mmol, 1.0 equiv) in anhydrous DCM (0.9 mL), the corresponding isocyanate (0.66 mmol, 1.5 equiv) was added dropwise at RT under Ar atmosphere. The reaction mixture was stirred until ap recipitate formed (3-16 h) and starting material had been consumed (TLC analysis).…”