Current Organic Chemistry - Volume 9, Issue 13, 2005

Organic chemistry promoted by indium metal and indium salts is of considerable current interest and a few reviews are available. In these reviews, however, applications to the field of heterocyclic chemistry is only scantily covered and the review "Indium Reagents in Heterocylic chemistry" by Dr. Subodh Kumar from the Department of Chemistry, Guru Nanok Dev University, Amritsar, India will, no doubt, be timely and useful. Ethyl ethoxymethylenecyanoacetate, EMCA, and diethyl ethoxymethylenemalonate, DEEM, are two useful reagents for the construction of heterocycles, for instance conversion of a monocyclic heterocycle to a bicyclic heterocycle. This chemistry has now been reviewed by Dr. Agnieska Kaczor from the Medical University of Lublin, Poland. Prof. Geza Stajer and Dr. Ferenc Csende from the Institute of Pharmaceutical Chemistry, University of Szeged, Hungary, have contributed the final two chapters dealing with synthetic approaches to isoindoles as well as 3-substituted isoindole-1-ones.

Indium due to its moderate heterophilicity and recyclability plays significant role in indium catalyzed / mediated reactions of heterocycles. The co-ordination of hetero atom of the heterocycle with indium and the electronic contributions of heteroatoms in the ring provide more versatility in comparison to acyclic and carbocyclic systems. Here, the applications of indium reagents in heterocyclic chemistry have been reviewed. The review discusses the applications of indium salts - both inorganic and organometallics in the transformations of three, four, five and six membered heterocycles; synthesis of heterocycles through cycloaddition, cyclocondensation reactions, intramolecular cyclization, cascade reaction and heterocyclic modifications on the ring or on the appendage etc.

This paper reviews on application of two Michael reagents - ethyl ethoxymethylenecyanoacetate (EMCA) and diethyl ethoxymethylenemalonate (DEEM, abbreviated also as DEMM, EMME or DEEMM) - in organic synthesis, especially in synthesis of biologically active compounds. The Michael reaction and its mechanism is tersely summarized, followed by examples of diversity of traditional and novel Michael donors and acceptors. Methods of synthesis of EMCA and DEEM are briefly described. Broad range of EMCA and DEEM use in synthesis of chain, cyclic, heterocyclic and fused heterocyclic structures is presented, focusing on the last ten years achievements. The chain derivatives are classified according to the type of atom (nitrogen, carbon, sulfur) which directly reacts with Michael reagent and adducts on the nitrogen atom are discussed with full particulars. Furthermore, possibilities of formation of cyclic compounds via cyanic or ester group are depicted and laboratory conditions for such reactions (especially for EMCA having both groups) are in each case given. Some attempts to generalize experimental results are made as they are supposed to facilitate prediction of the new processes products. The application of DEEM in preparation of registered drugs (quinolones, Rimazolium sulfate) is also recapitulated, because this reagent, as opposed to EMCA, is constantly used in contemporary pharmaceutical industry. Finally, our own results on reactions of 1-aryl-2-aminoimidazolines-2 with these two Michael reagents are reviewed with special emphasis on possibilities of isomeric enamine formation and ways of cyclization as well as on potential pharmacological activity of obtained compounds. Some computer modeling approaches to explain differentiated reactivity of DEEM and EMCA are also mentioned and critically discussed.

The development of novel synthetic methods for the preparation of condensed aromatic and saturated isoindolones containing one or more heteroatoms is described and several new types of related ring systems are presented. The frequently applied N-acyliminium ion cyclization, the cyclocondensation of dicarbonyl compounds (e.g. γ-oxoacids) with amines and the photoinduced intramolecular ring-closure of N-substituted phthalimides are utilized in the syntheses. The enantioselective and diastereoselective procedures with the ratios of the isomers obtained are also discussed.

Both direct and multistep reactions, involving the application of carbonyl compounds, e. g. oxoacids, phthalimides, 2-iodobenzamides or acylhalides, have been developed as novel synthetic routes for the preparation of 3- substituted 2,3-dihydro-1H-isoindol-1-ones, which are reviewed here. Alternatively, reductive or acid-catalyzed rearrangements of certain heterocycles lead to the formation of 3-substituted isoindolones. Asymmetric syntheses too have been described.