Spiro-fused heterocycles

Reaction of strong CH-acidic such as Meldrum s acid or barbituric acid derivatives, with aldehydes and urea was studied by Shaabani et al. this led to an efficient sol-vent-free synthesis of spiro-fused heterocycles by use of microwave irradiation [158]. 

The classic BigineUi three-component condensation [45,46] of aldehyde, urea or thiourea, and a dicarbonyl compound generating 3,4-dihydropyrimidin 2(lH)-one has been accomplished under solventless conditions to synthesize spiro-fused heterocycles in higher yields with shortened reaction time of a few minutes (Scheme 2.2-11) [47]. Purification was achieved by adding crushed ice to the reaction mixture, separating the solid via filtration and washing with cold water, followed by... 

The recent discovery of different types of biological activity in spiro-fused heterocyclic compounds has generated considerable interest among synthetic and medicinal organic chemists [124], The synthesis and chemistry of spiro-fused P-lactams have also developed steadily. Most of the methods apphcable to the synthesis of monocychc fS-lactams are apphcable with certain hmitations to the synthesis of spiro-fused 2-azetidinones [125]. The literature survey reveals the synthesis of several natural products inspired spiro-2-azetidinones having antimicrobial activity, cholesterol absorption inhibition activity, antiviral activity, and fS-lactamase inhibition activity [126]. 

The complex spiro-fused heterocycle (551) was obtained from the three components (548)-(550) via a domino process that involved the Michael addition and Diels-Alder cycloaddition. ... 

A domino total synthesis of spirotryprostatin B (2) and three of its isomers has been published by Overman and Rosen, who apply two sequential palladium-catalyzed reactions (one-pot) to assemble the two spiro-fused rings [10] (Scheme 3). This work again makes it clear that complex heterocyclic systems may represent a harder challenge to synthetic... 

We have studied the reaction of similar cyclic -substituted enaminones which yielded indolones when the reaction was carried out in acetic acid and the quinones had lower oxidation potential, thus preventing prior oxidation of the enaminones. Secondary aminomethylene derivatives of cyclopentanone, cyclohexanone and cycloheptanone reacted with the quinones to presumably form intermediate spiro compounds, as a consequence of normal enaminone chemistry. However, this was unexpectedly followed by rearrangement with ring expansion to indolones (equation 158). In this way carba-zoles, cycloheptindoles and cyclooctindoles can be obtained by a simple entry to this class of indoles, although partially in low yields222-224. Due to their bifunction-ality the produced indol-2-ones are versatile synthons for fused heterocycles (e.g. triazepino- and pyrazino-carbazoles) which become easily accessible225,226. 

In an attempted synthesis of the spiro compounds 123 from the cyclic 1,1-enediamines 122 derived from cyclic ketones, in contrast to the expectation, the cyclic ketone ring is cleaved under mild reaction conditions and fused heterocyclic compounds 124 are obtained in good yields from 122 and ethyl propiolate (equation 43)58,122. 

The rearrangements of some quinoline-4-spiro heterocycles to fused heterocycles have been reported, as has the thermal rearrangement of 4-alkoxy-3 -alkylthio-3,4 -diquinolinyl sulfides to 1-alkyl-1,4-dihydro-4-oxo-3 -aIkylthio-3,4 -diquinolinyl sulfides. It has been established that aqueous 6-hydroxyquinoline in the first excited singlet state undergoes protonation of the amine group first, then deprotonation firom the enol group, and finally rearrangement to the quinoid form. 

Syntheses and biological properties of isoquinolines spiro-fused at the 4-position with carbo- and heterocycles 02KGS1475. 

This account provides a summary of a chapter on Microwave Irradiation for Accelerating Organic Reactions in Advances in Heterocyclic Chemistry, volume 90, Part II Six, Seven-membered, Spiro and Fused Heterocycles by E. S. H. El Ashry, A. A. Kassem and E. Ramadan. Microwave irradiation (MWI) has been used extensively in organic synthesis. Application of MWI leads to many advantages, like the use of non-corrosive and inexpensive reagents, in addition to the eco-friendly "green chemistry" economical and environmental impacts. 

Keywords Microwave irradiation, green chemistry, organic synthesis, six and seven-membered heterocycles, spiro and fused heterocycles... 

The nucleophilic property of the thiocarbonyl group in enaminothiones give rise to a different manner of reaction with bifunctional groups. For example, a-bromoketones lead to thienoazepines with spiro-heterocycles as isolable intermediates. The reaction also takes place with benzo-fused heterocycles (equation 262). 

General reviews Tierney, J. R. and Lidstrom, R. (Eds), Microwave-Assisted Synthesis , Blackwell, 2005 Microwave irradiation for accelerating organic reactions. Rart I Three-, four- and five-membered heterocycles , El Ashry, E. S. H., Ramadan, E., Kassem, A. A. and Hagar, M., A v. Het-erocycl. Chem., 2005, 88,1 Rart II Six-, seven-membered, spiro, and fused heterocycles , El Ashry, E. S. H., Ramadan, E. and Kassem, A. K,Adv. Heterocycl. Chem., 2006, 90, 1. 

Microwave Irradiation for Accelerating Organic Reactions - Part II Six-, Seven-Membered, Spiro, and Fused Heterocycles... 

El Ashry, E. S. H., Kassem, A. A., Ramadan, E., Microwave Irradiation for Accelerating Organic Reactions - Part II Six-, Seven-Membered, Spiro, and Fused Heterocycles, 90, 1. 

Volume 90 of Advances in Heterocyclic Chemistry contains four chapters and the indexes. The book commences with Part II of Applications of Microwave Irradiation for Accelerating Reactions in Heterocycles. This continues Part I, which was published in Volume 88 of Advances in Heterocyclic Chemistry in 2005. Whereas Part I dealt with 3-, 4- and 5-membered heterocycles, the present Part II deals with 6-and 7-membered and spiro and fused heterocycles. Parts I and II have both been contributed by E. S. H. El Ashry, A. A. Kassem and E. Ramadan of Alexandria University, Egypt, and make available the large amount of recent work in this expanding area. 

Additionally, in what is termed a zipper cascade process, palladium-catalyzed reaction of 2-iodo-Af-tosylaniline (115), allenc and 2-iodothiophcne (116) provided the intermediate 117, which after cyclization was treated with boronic acids as capture reagents to provide the indolines 118 <01TL8677>. A similar approach was employed for the synthesis of spiro- and fused heterocycles <01CC964>. 

Microwave acceleration of reactions of six-, seven-membered, spiro and fused heterocycles 06AHC(90)1. 

A number of interesting A-ring-fused heterocycles have been synthesized from steroidaI-2,3-aziridines including thiazolines and imidazo[2,l-6]thiazo-lines, and a typical synthesis of the latter type from (280) is outlined in Scheme J2 225 spontaneous elimination of HCl from the intermediate (281) is noteworthy since the equivalent regioisomeric intermediate obtained from the 2a,3 -epimers of (280) is quite stable. A number of 17-spiro-oxazolidinones... 

In 2001, Grigg and co-workers reported a communication on the palladium-catalyzed cascade intramolecular cyclization of 2-iodobenzamides. ° The corresponding spiro- or linear fused heterocycles were produced in good yields (Scheme 3.14). The transformation involved the generation of a (7t-allyl)paHadium intermediate from the allene moiety. 

In the past decade, the chemistry of j0-lactam carbenes has proved successful for the construction of complex spiro- or fused heterocyclic scaffolds of medicinal relevance. To that purpose, their synthetic potential has been further explored with a study on their reactivity towards 3,6-di(2-pyrimidinyl)tetrazine (28). Diversely substituted / -lactam carbenes have been found to smoothly react with (28) to furnish the two novel heterocyclic scaffolds (29) or (30) depending solely on the reaction temperature (i.e., 100 and 140 °C, respectively) (Scheme 4). 

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