326594-18-7Relevant articles and documents
The effect of chiral: N-substituents with methyl or trifluoromethyl groups on the catalytic performance of mono-and bifunctional thioureas
Vazquez-Chavez, Josué,Luna-Morales, Socorro,Cruz-Aguilar, Diego A.,Díaz-Salazar, Howard,Vallejo Narváez, Wilmer E.,Silva-Gutiérrez, Rodrigo S.,Hernández-Ortega, Simón,Rocha-Rinza, Tomás,Hernández-Rodríguez, Marcos
supporting information, p. 10045 - 10051 (2019/12/23)
We evaluated thiourea organocatalysts that incorporate a chiral group which includes a trifluoromethyl moiety and contrasted their performance with non-fluorinated analogs. The comparison between such systems allows the direct study of the NH acidity of a thiourea bonded to an aliphatic substituent. In principle,-CF3 systems feature an enhanced hydrogen bond (HB) donor capacity that is undoubtedly beneficial for HB-catalysis applied to the Baylis-Hillman reaction. We found that the thiourea substituted on both nitrogens with this group accelerates this reaction like Schreiner's thiourea. On the other hand, we observed a different behavior in reactions promoted by bifunctional catalysts (thiourea-primary amine). In the Michael addition of isobutyraldehyde to methyl benzylidenepyruvate, the-CF3 containing catalysts were better than the-CH3 systems, whereas the conjugate addition to N-phenylmaleimide showed the opposite behavior. Theoretical calculations of the transition states indicated that the phenylethyl group in fluorinated and non-fluorinated compounds have different kinds of interactions with the electrophile. These interactions are responsible for a different arrangement of the electrophile and thereby the selectivity of the catalyst. Therefore, it cannot be generalized that in all cases NH acidity correlates with the performance of the catalyst, particularly, with aliphatic substituents that unlike the aromatic ones possess groups that are outside the plane of the thiourea.
Bifunctional Thioureas with α-Trifluoromethyl or Methyl Groups: Comparison of Catalytic Performance in Michael Additions
Jiménez, Eddy I.,Vallejo Narváez, Wilmer E.,Román-Chavarría, Carlos A.,Vazquez-Chavez, Josue,Rocha-Rinza, Tomás,Hernández-Rodríguez, Marcos
, p. 7419 - 7431 (2016/09/09)
Thioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis of bifunctional thioureas with a chiral moiety that include either a trifluoromethyl or methyl group. Their catalytic performance in representative Michael addition reactions was used in an effort to compare the electronic effects of the fluorination at the methyl group. The observed differences concerning yields and ee values cannot be attributed solely to the different steric environments; theoretical results indicate distinct interactions within the corresponding transition states. The calculated transition states show that the fluorinated catalysts have stronger N-H···O and C-H···F hydrogen bonds, while the nonfluorinated systems have C-H···π contacts. These results have shown that a variety of hydrogen-bonding interactions are important in determining the yield and selectivity of thiourea organocatalysis. These details can be further exploited in catalyst design.
