Phase-transfer catalyzed Michael/ammonolysis cascade reactions of enaminones and olefinic azlactones: a new approach to structurally diverse quinoline-2,5-diones

Abstract

A Michael/ammonolysis cascade reaction of cyclohexane-1,3-dione derived enaminones and olefinic azlactones via phase-transfer catalysis has been developed. This method provides rapid approach to a suite of architecturally complex and diverse...

A Three‐Component Domino Reaction Enabled by Phase‐Transfer Catalysis for the Assembly of 3‐Thioquinoline‐2,5‐Diones

“…In light of our recent work [12,19] we envisaged that cyclohexane-1,3-dione-derived enaminones and 5-alkenyl rhodanines are good reaction partners. Although the rhodanine motif is too stable to undergo sulfur functionalization through ring-opening, the strong alkalinity provided by Cs 2 CO 3 enables this chemical process.…”

“…We proposed a tentative mechanism for this phasetransfer-catalyzed three-component domino reaction based on preliminary experimental results, high-resolution mass spectrometry (HRMS) studies, and pre- vious literature [12,15] (Scheme 2). First, tetramethylammonium bromide (TMAB) is displaced by cesium carbonate on its solid surface to generate tetramethylammonium carbonate (TMAC), which enters the dichloromethane liquid phase.…”

“…Not detected. quinoline-2,5(1H,6H)-dione (12) in 95% yield. To our delight, product 6 b, whose side chain contains one more carbon atom than that of 4 a, was successfully substituted with iodide to yield compound 13, although the reaction required a higher temperature.…”

“…[9c-e,g,i] In 2022, we described a phasetransfer-catalyzed Michael/ammonolysis cascade reaction of enaminones and olefinic azlactones; this tactic successfully forged a CÀ N bond at the C-3 position of quinoline-2,5-dione. [12] Among the primary elements that comprise marketed drugs, sulfur is the fifth most abundant constituent (after carbon, hydrogen, oxygen, and nitrogen) and has a pivotal biological status in terms of overall architectural representation, owing to its unique properties. [13] Given the significance of sulfur in medicinal chemistry, constructing a CÀ S bond at the C-3 position of quinoline-2,5-dione may strengthen its interactions with receptors, [14] thereby endowing drug-discovery programs with high-quality prototype molecules.…”

“…As a continuation of our interests in developing phase-transfer catalytic strategies for assembling desirable heterocycles, [12,15] herein we report three-component domino chemistry involving cyclohexane-1,3dione-derived enaminones, [16] 5-alkenyl rhodanines, [17] and commercially available haloalkanes promoted by inexpensive quaternary ammonium salts in conjunction with inorganic alkalis. This astonishing reaction proceeded rapidly to deliver a structurally diverse set of 3-thioquinoline-2,5-diones in moderate-to-good yields and with excellent diastereoselectivities, thus realizing the concept of forging a CÀ S bond at the C-3 position (Figure 1).…”