Heterocycles polymer-supported reagents

Synthesis of Heterocycles Using Polymer-Supported Reagents under Microwave Irradiation... 

Scheme 3 Selected syntheses of heterocycles using polymer-supported reagents...

Heterocyclic compounds are of great interest to the pharmaceutical industry, as they make up most of the known pharmacophores. As a result, a number of libraries of various heterocycles have been prepared using polymer-supported reagents. While an exhaustive list of all the heterocychc cores that have been prepared using PSRs is beyond the scope of this chapter, some selected examples are depicted in Scheme 3. 

From a medicinal chemist s point of view, oxadiazoles are among the most important heterocycles as they are one of the most commonly used bioisosters for amide and ester groups [67]. As such it is hardly surprising that the two regioisomeric oxadiazole scaffolds received the most interest in the field of microwave-assisted synthesis using polymer-supported reagents. 

Crosignani S, Linclau B (2006) Synthesis of Heterocycles Using Polymer-Supported Reagents under Microwave Irradiation. I 129-154... 

Scheme 2.56 Polymer-supported reagents for heterocycle formation.

A number of N-brominated and N-chlorinated heterocycles also provide sources of electrophilic bromine. Examples include 1-chlorobenzotriazole (82JOC4895 87JOC173 88CHE36) and various HBr and Br2 adducts of pyridines, or pyridine perbromides [84SC939 85JAP(K)60/87264], Polymer-supported reagents of this type include 1-cyclohexylpyridinium perbromide linked to polystyrene, effective for the bromination of 1-methylindole, benzo[fc]furan, and benzo[6]thiophene (89T7869). 

Parlow, J. J. Mischke, D. A. Woodard, S. S. Utility of Complementary Molecular Reactivity and Molecular Recognition (CMR/R) Technology and Polymer-Supported Reagents in the Solution-Phase Synthesis of Heterocyclic Carboxamides, /. Org. Chem. 1997,62, 5908. 

JJ Parlow, DA Mischke, SS Woodard. Utility of complementary molecular reactivity and molecular recognition (CMR/R) technology and polymer-supported reagents in the solution-phase synthesis of heterocyclic carboxamides. J Org Chem 62 5908-5919, 1997. 

In related work, rapid synthesis of 1,2,4-oxadiazoles was achieved on polymer-supported reagents [109]. Two independent pathways were used to prepare these heterocycles from carboxylic acids and amidoximes under the action of microwave irradiation. In accordance with the conventional method using HBTU and N,N-diisopropylethylamine (DIEA) for synthesis of this heterocycle, a method utilizing polymer-supported bases was employed. The use of PS-BEMP in the presence of HBTU proved to be beneficial in the microwave procedure. Heating for 15 min in acetonitrile at 160 °C furnished high yields for a series of substrates. 1,2,4-Oxadiazoles can also be synthesized from carboxylic acid chlorides. Because these... 

Baxendale, I.R., Davidson, T.D., Ley, S.V. and Pemi, R.H. (2003) Enantioselective synthesis of the tetrahydrobenzylisoquinoline alkaloid (—)-norarmepavine using polymer supported reagents. Heterocycles, 60, 2707-2715. 

---