Kinetic Resolution of β‐Sulfonyl Ketones through Enantioselective β‐Elimination using a Cation‐Binding Polyether Catalyst

Abstract

Reported herein is the first enantioselective β-elimination reaction catalyzed by a chiral cation-binding polyether. By using this catalytic protocol, a wide range of β-sulfonyl ketones could be effectively resolved with high stereoselectivity (S up to >300). Key to the success of this process is the favorable secondary interactions of the catalyst with the Lewis basic groups on the sulfone substrate. The enone product of this process can be easily converted into the racemic starting material, and allows an effective recycling and overall synthesis of chiral β-sulfonyl ketones in high yield and excellent enantioselectivity.

Chiral exploration of 6,12‐diphenyldibenzo[b,f][1,5]diazocine with stable conformation

“…Recently, the concept of conformational chirality based on axial and planar chiral molecules has become a topic of intense interest . Different kinds of structures with the restricted rotation of σ‐bonds such as biaryls, cyclophanes, and strained cyclic alkenes have been developed for asymmetric catalysis, functional materials, supramolecular chemistry, targets of total synthesis, and so on …”

Biomimetic catalytic transformation of toxic α-oxoaldehydes to high-value chiral α-hydroxythioesters using artificial glyoxalase I

“…As per our expectations, the hemithioacetal 4a was formed as a racemic form almost spontaneously under the reaction conditions and its enantioselective isomerization proceeded smoothly, affording the desired enantioenriched 5a . Based on our knowledge of the catalytic performance of chiral oligoEGs 1 (refs 26, 27, 28, 29, 30), the presence of the polyether backbone, the ether chain length (entries 6 and 7) and the acidity of phenolic protons (entry 2 versus entry 4) are crucial in achieving the catalytic activity and enantioselectivity. Although ( R )- 1c showed distinguished catalytic activity and enantioselectivity (see, entry 3) compared to ( R )- 1a and ( R )- 1b (entries 1 and 2, respectively), the observed activity and enantioselectivity were still unsatisfactory (68% conversion and 87% ee after 48 h).…”

“…Therefore, developing powerful biomimetic catalytic system is highly interesting from the perspectives of both biology and chemistry. Given our previous studies on our evolved cation-binding catalyst 1 (refs 26, 27, 28, 29, 30), we presumed that catalyst 1 could act as a synthetic glyoxalase I for the enantioselective isomerization of the spontaneously formed hemithioacetal adduct between thiols and α-oxoaldehydes into enantio-enriched α-hydroxythioesters. The hydrogen-bond chelating interaction between the acidic phenolic protons of the catalyst and two oxygen atoms of hemithioacetals would enhance the electrophilicity of the carbonyl carbon atom, consequently increasing the acidity of the α-proton.…”

Asymmetric Synthesis of Diarylmethyl Sulfones by Palladium‐Catalyzed Enantioselective Benzylic Substitution: A Remarkable Effect of Water

“…In 2016, Yan reported the chiral cation‐binding poly ether catalyst for enantioselective elimination of racemic β‐sulfonyl ketones. Although the enantioselectivity was excellent, the reaction proceeded in a kinetically resolved manner, thus giving the chiral sulfones in chemical yields theoretically up to 50 % . Stereoconvergent approaches to chiral sulfones from racemic starting substrates are more attractive from the viewpoint of atom economy (Scheme ).…”