Bifunctional Thioureas with α-Trifluoromethyl or Methyl Groups: Comparison of Catalytic Performance in Michael Additions

Abstract

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.

Acidity and basicity interplay in amide and imide self-association

“… 4 Additionally, the dimerisation of amides and imides is of interest in several fields such as supramolecular chemistry in which the self-recognition of these functional groups is relevant. 5 , 6 …”

Crosslinked Resin‐Supported Bifunctional Organocatalyst for Conversion of CO2 into Cyclic Carbonates

“…On the basis of catalyst performance and the homogeneous catalyst demonstrated in recent studies, a possible dual cooperative activation mechanism was proposed for the cycloaddition reaction of CO 2 with the epoxide to form cyclic carbonate by P‐C m3 L m1 N m2 (Scheme a). Firstly, the two hydrogen atoms in the thiourea unit worked as the Lewis‐acidic components in the system to activate the epoxy substrate through hydrogen bonds, and the activated C−O bond was easy to be ring‐opened by the nucleophilic Br − anion, resulting in the intermediate 1 .…”

A Recyclable Hydrophobic Anchor‐Tagged Asymmetric Amino Thiourea Catalyst

“…Application of the recyclable catalyst 6 to an asymmetric Michael reaction was next examined (Scheme ). The reaction of nitrostyrene 19 a or 19 b with acyclic dicarbonyl compounds such as diethyl malonate 20 or acetylacetone 21 in the presence of 30 mol % of catalyst 6 in toluene at 30 °C proceeded smoothly to yield desired Michael adducts 24 a – d in high chemical and optical yields. The reaction with cyclic‐type nucleophiles 22 and 23 in CH 2 Cl 2 also proceeded in an enantioselectively, generating desired products 24 e – f and 24 g – h in high chemical yields.…”