Dynamic Kinetic Resolution of Azlactones by Bifunctional Thioureas with α‑Trifluoromethyl or Methyl Groups

Abstract

The asymmetric ring opening of azlactones via dynamic kinetic resolution (DKR) is investigated by contrasting thioureas incorporating 1-arylethyl substituents against their more acidic trifluoromethylated analogs. All the catalysts under study outperform Takemoto’s thiourea because of the inclusion of an additional chiral center. However, the difference in yield and selectivity between the fluorinated and non-fluorinated catalysts is minimal. We explain this observation by analysis of calculated transition states. Our findings show that the hydrogen bond (HB) between the NH linked to the 1-arylethyl and the negatively charged oxygen in the benzyloxy ion is the longest in the HB network, whereas the HB between the ammonium group and the same oxygen atom is the shortest. Thus, the substituents and the HB donor ability of this chiral fragment attached to the thiourea are not important in the reaction.

An update on chiral phosphoric acid organocatalyzed stereoselective reactions

“…Chen, Huang, and co-workers reported the enantioselective intramolecular [2,3]-sigmatropic rearrangement of aldehydes via a sulfonium enamine intermediate (Scheme 52). 139 Initially, the authors proposed a pathway that starts with the α-iodination of the aldehyde enabled by the amine to form intermediate A.…”

“…Examples of organocatalysts that partially transfer a proton are thioureas, squaramides, and diols. [1][2][3][4][5][6] On the other hand, catalysts that completely transfer a proton to the substrate are Chiral Phosphoric Acids (CPAs), N-triflyl phosphoramides, chiral disulfonimides, and imidodiphosphate-type Brønsted acids. [7][8][9][10][11] Since the first report in 2004, chiral phosphoric acids have been establishing new trends with robust synthetic protocols and are undoubtedly the reference in Brønsted acid-type organocatalysis.…”

“…Examples of organocatalysts that partially transfer a proton are thioureas, squaramides, and diols. 1–6 On the other hand, catalysts that completely transfer a proton to the substrate are Chiral Phosphoric Acids (CPAs), N -triflyl phosphoramides, chiral disulfonimides, and imidodiphosphate-type Brønsted acids. 7–11…”