Synthesis of spiro-linked quinolinone-pyrrolidine/pyrrolo[1,2-c]thiazole-oxindole/acenaphthalene hybrids via multi-component [3 + 2] cycloaddition

Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

“…Some succinimide derivatives, for instance, are used as antimycobacterial for treatment of Mycobacteria infections, [44,45] to suppress cancer cell proliferation [46] and act as anticonvulsant agents [47,48] (Figure 2). Among the typical synthetic strategies leading to these spiroheterocyclic scaffolds, the multicomponent 1,3-dipolar cycloaddition of electron-deficient exocyclic alkenes with azomethine ylides, generated in situ from α-aminoacids and 1,2-diketones, is the most widely reported one [35][36][37][38][39][40][41]. Its process simplicity combined with mild reaction conditions and atomic economy addresses several aspects required for combinatorial chemistry.…”

Synthesis and Cytotoxic Evaluation of 2-Aryl-7,8-dihydroquinolin-6(5H)-ones

“…It is well-known that a common intermediate in the classical synthesis of pyridines is the in situ formation of 1,5-dicarbonyl compounds, which take advantage of the Michael addition reaction. Thus, we envisioned forming 1,5-dicarbonyl compounds by the reaction of Mannich salts with cyclohexanone 18 or from cyclohexanone-derived enaminones. [19][20][21] In this work, cyclohexane-1,4-dione monoethylene acetal (8) was utilized.…”

“…The synthesis started with protection of the hydroxy group of 16c with benzyl bromide to afford 16r in quantitative yield, acetophenone derivative 16r and DMF-DMA (18) were refluxed in xylene to provide 19 in good yield, enaminone 19 was reacted with cyclohexane-1,3-dione (20) and ammonium acetate to produce dihydroquinolin-5(6H)-one 21 in 60% yield, and finally hydrogenolysis mediated with Pd/C provide 22 in good yield.…”

Domino synthesis of functionalized pyridine carboxylates under gallium catalysis: Unravelling the reaction pathway and the role of the nitrogen source counter anion

“…The pioneering work of Bohlmann and Rahtz [6] triggered incessant efforts for the development of newer methodologies for the synthesis of substituted pyridines that involve the reaction of β‐enamino esters ( I ) and ethynyl ketones ( II ) which are either pre‐formed [7] or generated in situ from the corresponding β‐ketoesters/β‐ketoamides [8] ( III ) and the propargyl alcohols/silyl ethers [9] ( IV ), respectively (Scheme 1, route A) to give an aminodienone intermediate ( V ) that undergoes intramolecular cyclodehydration‐aromatization on heating under vacuum at 120–140 °C or under mild condition in the presence of catalysts (NBS/NIS/I 2 /ZnBr 2 ) [8e,10] or μW irradiation [11] or in the presence of Brønsted acidic catalyst [7c,12] . The other approaches are the: (a) reaction of β‐enamino esters ( I ) with enones ( VI ), [13] generated in situ from the acetophenone Mannich base hydrochlorides ( VII ) [14] via retro ‐aza Michael reaction or generated in situ by the oxidative transformation of allylic alcohols ( VIII ) [15] /inactivated ketones ( IX ) [16] or from aldehyde and ketones by base‐promoted aldol condensation [17] (Scheme 1, route B), (b) reaction of oxazolidines ( X ) substituted at C‐2 with CH 2 ‐EWG (capable of existing as ring‐chain tautomer) with β‐enamino esters ( I ) in refluxing MeCN and acetic acid (Scheme 1, route C), [18] (c) reaction of (2 E )‐3‐(dimethylamino)‐1‐arylprop‐2‐en‐1‐ones ( XI ) with active methylene group containing ketones ( XII ) in the presence of ammonium acetate (Scheme 1, route D) in refluxing acetic acid, [19] under Lewis acid catalyst, [20] or organocatalyst [21] . Other approaches are: ring expansion of allyl azirines ( XIII ) via base promoted azirine ring opening followed by intramolecular cyclization of the imine dienes (Scheme 1, route E), [22] intramolecular cyclization of dienone oximes ( XIV ) through visible light promoted single electron transfer in the presence of iridium photocatalyst followed by generation of iminyl radical and oxidative C−N bond formation (Scheme 1, route F), [23] and the reaction of β‐enamino esters ( I ) with cyclobutanones ( XV ) to give an imine intermediate followed by ring opening and nucleophilic intramolecular cyclization in presence of Lewis acid (Scheme 1, route G) [24] .…”

“…[7c,12] The other approaches are the: (a) reaction of β-enamino esters (I) with enones (VI), [13] generated in situ from the acetophenone Mannich base hydrochlorides (VII) [14] via retro-aza Michael reaction or generated in situ by the oxidative transformation of allylic alcohols (VIII) [15] / inactivated ketones (IX) [16] or from aldehyde and ketones by base-promoted aldol condensation [17] (Scheme 1, route B), (b) reaction of oxazolidines (X) substituted at C-2 with CH 2 -EWG (capable of existing as ring-chain tautomer) with β-enamino esters (I) in refluxing MeCN and acetic acid (Scheme 1, route C), [18] (c) reaction of (2E)-3-(dimethylamino)-1-arylprop-2-en-1ones (XI) with active methylene group containing ketones (XII) in the presence of ammonium acetate (Scheme 1, route D) in refluxing acetic acid, [19] under Lewis acid catalyst, [20] or organocatalyst. [21] Other approaches are: ring expansion of allyl azirines (XIII) via base promoted azirine ring opening followed by intramolecular cyclization of the imine dienes (Scheme 1, route E), [22] intramolecular cyclization of dienone oximes (XIV) through visible light promoted single electron transfer in the presence of iridium photocatalyst followed by generation of iminyl radical and oxidative CÀ N bond formation (Scheme 1, route F), [23] and the reaction of β-enamino esters (I) with cyclobutanones (XV) to give an imine intermediate followed by ring opening and nucleophilic intramolecular cyclization in presence of Lewis acid (Scheme 1, route G). [24] However, some notable disadvantages of these reported methods such as the lack of ease of availability of the requisite starting materials, harsh reaction conditions, long reaction time, poor to moderate yields, use of an excess of reagents/catalysts, use of volatile organic solvents, and limited substrate scope necessitates the development of the more convenient procedure.…”