Darzens reaction of thioisatins and sulfonium salts: approach to the synthesis of thiochromenone derivatives with anticancer potency

Abstract

A new Darzens reaction of thioisatins and sulfonium salts has, for the first time, been reported. This reaction allows efficient access to thiochromenone derivatives in good to excellent yields under mild reaction conditions. The substrate scope includes both electron-withdrawing and electron-donating groups on both the thioisatins and sulfonium salts. Moreover, some of the synthesized thiochromenone derivatives have been found to show potent anticancer activities against six different cancer cell lines using the methylthiazoltetrazolium (MTT) assay.

Amine‐Mediated Domino Reaction of Thioisatins: Synthesis of Benzothiophene‐fused N‐Heterocycles under Catalyst‐Free Conditions

“…According to our previous research and related reports, [6b,9] a possible reaction mechanism for this domino reaction is proposed in Scheme 5. Initially, amine attack the C2 position of thioisatins 1 to generate the intermediate A , and then, the S − center in intermediate A attack 2‐bromo‐1‐phenylethan‐1‐one to generate the intermediate B .…”

“…Later, Matsubara developed a nickel/phosphine catalytic system to achieve the cycloaddition of thioisatins with alkynes [8] . Recently, our group disclosed a Cs 2 CO 3 promoted [5+1] cycloaddition of thioisatins with sulfur ylides, furnishing a variety of thiochromenones in good yields (Scheme 1b) [6b] . Furthermore, our group realized an amine‐promoted reaction of thioisatins with α‐bromoketines in water (Scheme 1b) [9] .…”

Divergent Construction of Benzothiophene-Fused N-Heterocycles via Stereotunable Three-Component Domino Reactions

“…Furthermore, the C–S bond could be easily cleaved in the presence of inorganic bases or amines . For example, reactions of thioisatin with sulfur ylides in the presence of Cs 2 CO 3 produced a series of thiochromenones with good anticancer potency . In addition, our group reported an amine-mediate domino reaction of thioisatin in water .…”

“…10 For example, reactions of thioisatin with sulfur ylides in the presence of Cs 2 CO 3 produced a series of thiochromenones with good anticancer potency. 11 In addition, our group reported an amine-mediate domino reaction of thioisatin in water. 12 In this context, we envisioned that diverse benzothiophene-fused heterocycles may be synthesized by a cyclohexane-1,2-diamine-mediate stereotunable domino reaction (Figure 2).…”

Construction of Benzothiophene Fused Pyrrolidone in Water under Catalyst-Free Conditions

“…近年来, 多米诺反应为多种环类化合物的合成提供 了高原子经济性和步骤经济性策略 [7] . 天津理工大学化 学化工学院孟祥太课题组 [8] 致力于杂环化合物的绿色多 米诺构筑方法研究, 在无金属条件下实现了以硫代靛红 为原料的多样性导向合成, 用于多类含硫环状化合物的 高效构筑(图 1a). 近日, 该团队 [9]…”