Isoxazoles are important five-membered aromatic heterocycles in organic chemistry. Recently, many exciting advances in the synthesis and functionalization of isoxazoles have been reported. New transition metal-catalyzed reactions have resulted in the development of attractive and highly efficient synthetic approaches to densely functionalized isoxazoles. Complete control of regioselectivity can be achieved on the basis of a judicious choice of metal catalyst and reaction partners using dipolar cycloaddition and cycloisomerization reactions, while more recent studies have focused on the site-selective functionalization of isoxazoles via CH functionalization. New strategies for the use of isoxazoles as scaffolding templates in asymmetric synthesis have emerged, thus opening new prospects for the synthesis of enantioenriched motifs under the conditions that are orthogonal to other transformations. In this review, recent advances involving the synthesis and reactivity of isoxazoles are summarized. The review covers the period from January 2005 to June 2015.

Recent Developments in the Synthesis and Reactivity of Isoxazoles: Metal Catalysis and Beyond

4-Thiazolidinones: the advances continue….

Mannich bases in medicinal chemistry and drug design.

The molecular structures and spectral properties of α-haloketones as well as their syntheses are analyzed and reviewed. Their reactivity towards oxygen, nitrogen, and sulfur nucleophiles, carboxylic acids, carbon nucleophiles, alkenes, and alkynes are discussed.

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The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis

Amino acids and amines have been used to catalyze three component hetero-domino Knoevenagel/Diels−Alder/epimerization reactions of readily available various precursor enones (1a−l), aldehydes (2a−p), and 1,3-indandione (3). The reaction provided excellent yields of highly substituted, symmetrical and nonsymmetrical spiro[cyclohexane-1,2‘-indan]-1‘,3‘,4-triones (5) in a highly diastereoselective fashion with low to moderate enantioselectivity. The Knoevenagel condensation of arylaldehydes (2a−p) and 1,3-indandione (3) under organocatalysis provided arylidene-1,3-indandiones (17) in very good yields. We demonstrate for the first time amino acid- and amine-catalyzed epimerization reactions of trans-spiranes (6) to cis-spiranes (5). The mechanism of conversion of trans-spiranes (6) to cis-spiranes 5 was shown to proceed through a retro-Michael/Michael reaction rather than deprotonation/reprotonation by isolation of the morpholine enamine intermediate of cis-spirane (22). Prochiral cis-spiranes (5ab) and trans...

https://www.scripps.edu/barbas/pdf/RamcharyJOC04.pdf

Direct organocatalytic asymmetric heterodomino reactions: the Knoevenagel/Diels-Alder/epimerization sequence for the highly diastereoselective synthesis of symmetrical and nonsymmetrical synthons of benzoannelated centropolyquinanes.

In this project, an effective procedure for constructing a new combination of pyrazolo[3,4‐b]pyridine was depicted through the coupling of diazonium salt 2 of heterocyclic amine 1 with active methylene, enamine, and amidine moieties such as 3, 5, 7, and 9 at 0–5 °C in pyridine to afford hydrazinylhydrazonoyl derivatives 4, and diazenylheterocyclic derivatives 6, 8, and 10, respectively. Also, aminopyrazolo[3,4‐b]pyridine 1 condensed with different aryl or heteroaryl aldehydes in EtOH/AcOH gave the corresponding aldimine 14, 15, 16. Compound 15 was cyclized via refluxing in DMF for 6 h to afford 18, while the transformation of compound 16 with an alkyl halide afforded 19a, b. The synthesized compounds, explicated by spectral data and elemental analysis, were examined for their antitumor activities. The in vitro cytotoxic activity of new pyrazolo[3,4‐b]pyridines against the A2780CP, MCF‐7, and HepG‐2 cell lines was evaluated using the reference doxorubicin. Compounds 15 and 19a exhibited high reactivity against the A2780CP cell lines, with IC50 values of 35 and 17.9 μM, respectively. Also, compound 28 had the cytotoxic potential for A2780CP and MCF‐7 cell lines, with IC50 values of 14.5, and 27.8 μM, respectively.

An Efficient Approach for the Synthesis and Antitumor Evaluation of Novel Azo‐ and Anil‐Linked with 3‐Aminopyrazolo[3,4‐b]pyridine

Condensation of 3,5-dinitro-4-chloro-6-methoxy-2-methylquinoline (1) with benzylamine, ethanolamine and/or thioglycolic acid afforded the quinoline derivatives4 a-c. Cyclization of4 a and4 b with alkali and condensation of1 with glycine in sodium carbonate solution furnish 2H-imidazo[4,5-c]quinoline derivatives5 a-c, respectively. Treatment of5 b with benzaldehyde in presence of zinc chloride gave the styryl derivative6. 1 reacted with sodium azide to give the azido derivative4 d, which upon treatment with phenylhydrazine or sodium borohydride yielded the 4-amino derivative4 3. Moreover,1 was treated with phenylhydrazine to give4 f, which cyclized in 10% sodium hydroxide solution to the corresponding v-triazolo[4,5-c]quinoline 3-oxide derivative7. When however4 f was treated with dilute hydrochloric acid, the corresponding phenylpyrazolo[3,4,5-de]quinoline derivative8 was obtained.

Base induced cyclization of some quinolines. formation of fused nitrogen heterocyclic ring system

Mannich reaction of 1,3-indandione-1-phenylhydrazone (1) or 1,3-diphenylhydrazone(5) with morpholine or piperazine gave the Mannich base-phenylhydrazone 2 and 3 or the diphenylhydrazone 6 and 7, respectively. Whereas, such reaction with 1 or 5 using primary amines afforded the indeno [2,1-f]-1,2,4-triazepin-6(2H)-one (4) or its 6-phenylhydrazone (8), respectively. Treatment of 5 with ammonium acetate and formalin afforded 9. The indeno [1,2-f]-1,2,4,5-tetrazepin-10(2H)-one (11) was obtained from the 1,2-diphenylhydrazone 10 and formaldehyde

Hanafi H. Zoorob

Papers

An Efficient Approach for the Synthesis and Antitumor Evaluation of Novel Azo‐ and Anil‐Linked with 3‐Aminopyrazolo[3,4‐b]pyridine

Base induced cyclization of some quinolines. formation of fused nitrogen heterocyclic ring system

Mannich Reaction with 1,3-Indandione Phenylhydrazones.

Introduction of Some Pharmaceutically Active Heterocycles into the Benzylic Moiety of 2-Benzyl-1,3-indandione.

Synthesis and Characterization via Molecular Quantum Parameters of 2H‐Thiazolo[3,2‐a]pyrimidine‐3,5,7(6H)‐trione (III).