Novel applications of microwave-assisted cyclizations promoted by polyphosphoric acid esters PPE and PPSE

LILIANA R. ORELLI; MARÍA CRUZ MOLLO; JIMENA E. DÍAZ; NADIA GRUBER

Oporto

Simposio; Terceiro Simposio Iberoamericano de Quimica Organica; 2016

Faculdade de Ciencias. Universidade do Porto

Presentación oral. NOVEL APPLICATIONS OF MICROWAVE-ASSISTED CYCLIZATIONS PROMOTED BY POLYPHOSPHORIC ACID ESTERS PPE AND PPSE. Orelli LR, Mollo MC, Díaz JE, Gruber N. Universidad de Buenos Aires. CONICET. Departamento de Química Orgánica. Facultad de Farmacia y Bioquímica. Junín 956, (1113) Buenos Aires, Argentina. Email: lorelli@ffyb.uba.ar. Ethyl polyphosphate (PPE) and trimethylsilyl polyphosphate (PPSE) are mild irreversible dehydrating agents of the Lewis acid type. These reagents are stable, non toxic and readily available from inexpensive precursors. They generate water soluble subproducts with no negative environmental impact. PPE and PPSE have been widely used for several synthetically useful transformations, including heterocycles syntheses. Cyclocondensation is one of the most important methods for the synthesis of heterocycles, and microwave heating has found interesting applications in this area.1 In particular, it has enabled the synthesis of the more challenging medium size (7-9 membered) heterocycles by overcoming limitations arising from low reactivity and yields.2 In this context, as part of ongoing research of our group,3 we report here some novel applications of PPE and PPSE to microwave-assisted ring closure reactions leading to 1,3-O,N-, S,N- and N,N- heterocycles. The first group of compounds comprises 2-oxazolines 1 and their 6 and 7-membered homologues 2,3, which were efficiently synthesized by cyclization of omega-hydroxyalkylamides. The second group includes 2-aryl-4,5,6-tetrahydro-1,3-thiazepines 4 and their lower homologues, for which two alternative synthetic approaches were investigated. 1,3-N,N-heterocycles comprise 5 to 7-membered 1-aryl-2-iminoazacycloalkanes 5-7 and 1-aryl-2-substituted-3,4-dihydroquinazolines 8. We discuss the reaction mechanisms and the role of PPA esters in the cyclizations, which varies according to the nature of the acyclic precursors.In all cases, the cyclizations promoted by PPE/PPSE performed under microwave irradiation afforded good to high yields of the desired heterocycles in remarkably short reaction times. The successful results obtained on seven membered heterocycles 3,4,7 are of particular relevance, as no general methods are available for their synthesis. AcknowledgementsThis work was supported by the University of Buenos Aires (Grant 20020130100466). References(1) Van der Eicken E, Kappe C O. Microwave-Assisted Synthesis of Heterocycles; Distribution Center, GmbH, 2006.(2) Sharma A, Prasad A, Van der Eycken E. Chem. Commun. 2012, 48, 1623-1637.(3) Díaz JE, Gruber N, Orelli LR. Tetrahedron Lett. 2011, 52, 6443-6445 and references therein.