title: Prins Cyclization Catalyzed by a Fe(III) /Trimethylsilyl Halide System: The Oxocarbenium Ion Pathway versus the [2+2] Cycloaddition.
abstract: The different factors that control the alkene Prins cyclization catalyzed by iron(III) salts have been explored by means of a joint experimental-computational study. The iron(III) salt/trimethylsilyl halide system has proved to be an excellent promoter in the synthesis of crossed all-cis disubstituted tetrahydropyrans, minimizing the formation of products derived from side-chain exchange. In this iron(III)-catalyzed Prins cyclization reaction between homoallylic alcohols and non-activated alkenes, two mechanistic pathways can be envisaged, namely the classical oxocarbenium route and the alternative [2+2] cycloaddition-based pathway. It is found that the [2+2] pathway is disfavored for those alcohols having non-activated and non-substituted alkenes. In these cases, the classical pathway, via the key oxocarbenium ion, is preferred. In addition, the final product distribution strongly depends upon the nature of the substituent adjacent to the hydroxy group in the homoallylic alcohol, which can favor or hamper a side 2-oxonia-Cope rearrangement.
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, C/Francisco Sánchez 2, 38206 La Laguna, Tenerife (Spain), Fax: (+34) 922318571.
authors.forename: Sixto J
authors.initials: SJ
authors.lastname: Pérez
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, C/Francisco Sánchez 2, 38206 La Laguna, Tenerife (Spain), Fax: (+34) 922318571.
authors.forename: Martín
authors.initials: M
authors.lastname: Purino
authors.affiliation: Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (CSIC), C/Francisco Sánchez 3, 38206 La Laguna, Tenerife (Spain), Fax: (+34) 922260135.
authors.forename: Pedro O
authors.initials: PO
authors.lastname: Miranda
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, C/Francisco Sánchez 2, 38206 La Laguna, Tenerife (Spain), Fax: (+34) 922318571. vmartin@ull.es.
authors.forename: Víctor S
authors.initials: VS
authors.lastname: Martín
authors.affiliation: Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid (Spain). israel@quim.ucm.es.
authors.forename: Israel
authors.initials: I
authors.lastname: Fernández
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, C/Francisco Sánchez 2, 38206 La Laguna, Tenerife (Spain), Fax: (+34) 922318571. jipadron@ipna.csic.es.|Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (CSIC), C/Francisco Sánchez 3, 38206 La Laguna, Tenerife (Spain), Fax: (+34) 922260135. jipadron@ipna.csic.es.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Padrón
keywords: Lewis acids; cyclization; density functional calculations; heterocycles; iron