Polymer-supported reactions heterocyclizations

Abstract An overview on the microwave-enhanced synthesis and decoration of the 2(lH)-pyrazinone system is presented. Scaffold decoration using microwave-enhanced transition-metal-catalyzed reactions for generating structural diversity, as well as the conversion of the 2(lH)-pyrazinone skeleton applying Diels-Alder reactions to generate novel heterocyclic moieties are discussed. The transfer of the solution phase to polymer-supported chemistry (SPOS) is also described in detail. 

The best results in the imidazole synthesis were obtained by microwave-assisted reaction of an eightfold excess of the polymer-supported isonitrile suspended in 1,2-dimethoxyethane (DME) with the appropriate amines. Cleavage with 50% trifluoroacetic acid in dichloromethane afforded the desired heterocyclic scaffolds in moderate yields. 

Steel PG, Teasdale CWT. Polymer supported palladium A-heterocyclic carbene complexes long lived recyclable catalysts for cross coupling reactions. Tetrahedron Lett 2004 45 8977-8980. 

The chemo- and regiospecific palladium-catalyzed four-component reaction of aryl iodides followed by incorporation of carbon monoxide, a polymer-supported allene, and a range of secondary cyclic amines has been reported as a short and high-yielding route to complex heterocycles with three points of diversity, such as 7 <2000CC2241>. 

Xu, W. Mohan, R. Morrissey, M. M. Polymer Supported Bases in Solution-Phase Synthesis. 2. A Convenient Method for /V-Alkylation Reactions of Weakly Acidic Heterocycles, Bioorg. Med. Chem. Lett. 1998, 8, 1089. 

This may imply that the intermolecular coupling of various aryl halides with other heteroaromatic compounds may proceed. Indeed, it is now known that not only the special heteroaromatic halides but also usual aryl halides can react with a variety of five-membered aromatic heterocycles, including furans, thiophenes, and azole compounds such as M-substituted imidazoles, oxazoles, and thiazoles [133-137]. The arylation of azoles can be carried out using iodobenzoate immobilized on an insoluble polymer support [138]. Related intermolecular reactions of indole [139] and imidazole [140] derivatives have also been reported. 

The bond between carbon and rhodium is extremely stable, thus allowing mono- or biphasic hydroformylations without any excess of ligands. Due to this stability, for the first time ever an anchoring to a polymer support seems possible without leaching. These N-heterocyclic carbenes appear to be excellent ligands to stabilize catalytically active metals even under harsh temperature conditions, e. g. Heck C-C-coupling reactions at 130 °C [152 b]. 

Fu and Shuttleworth (03TL3843) (Scheme 14) set out to develop conditions for A -acylating 5-aminopyrazol-3-ones used in previous years as building blocks in the construction of 6,5-fused heterocycles. The simple reaction of 5-aminopyrazol-3-one 51 with 2-thiophenecarbonyl chloride 52 in DMF in the presence of polymer-supported Hunig s base 53, however, turn out to be extremely capricious. Under... 

Preparation. - A range of 1,3-dithianylphosphonium salts (218) has been prepared in the course of further studies of sulfur lone pair anomeric effects in these systems.Conventional quatemization reactions have been used in the synthesis of the salt (219) and a range of polymer-supported phosphonium salts (220). A new efficient route to salts of the type (221) has been developed. The of>-azolylalkylphosphonium salts (222) are readily accessible from the reactions of the corresponding a>-bromoalkylphosphonium salts and azoles. Routes to vinylphosphonium salts, e.g., (223), continue to be explored, and their reactivity utilised in the synthesis of phosphonium salts bearing heterocyclic substituents, e.g., (224). The betaine (225) has been... 

Microwave-assisted solid-phase synthesis of purines on an acid-sensitive meth-oxybenzaldehyde (AMEBA)-linked polystyrene has been reported [50]. The heterocyclic scaffold was first attached to the polymer support via an aromatic nucleophilic substitution reaction by conventional heating in l-methyl-2-pyrrolidinone (NMP) in the presence of N,N-diisopropylethylamine. The key aromatic nucleophilic substitution of the iodine with primary and secondary amines was conducted by microwave heating for 30 min at 200 °C in l-methyl-2-pyrrolidone (Scheme 16.28). After reaction the products were cleaved from the solid support by use of trifluoroacetic acid-water at 60 °C. 

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