Millán, RamónRodríguez, JaimeSarandeses, Luis A.Gómez Bengoa, EnriquePérez Sestelo, José2021-10-292021-10-292021-06-25Millán, R. E.; Rodríguez, J.; Sarandeses, L. A.; Gómez-Bengoa, E.; Sestelo, J. P. J. Org. Chem. 2021, 86, 9515. https://doi.org/10.1021/acs.joc.1c008250022-32631520-6904http://hdl.handle.net/2183/28771Financiado para publicación en acceso aberto: Universidade da Coruña/CISUGThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.1c00825 (https://pubs.acs.org/doi/suppl/10.1021/acs.joc.1c00825/suppl_file/jo1c00825_si_001.pdf)[Abstract] The indium(III)-catalyzed cascade cycloisomerization reaction of 1,5-enynes with pendant aryl nucleophiles is reported. The reaction proceeds in cascade under mild reaction conditions, using InI₃ (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene (E and Z isomers) and with terminal and internal alkynes. Using 1-bromo-1,5-enynes, a one-pot sequential indium-catalyzed cycloisomerization and palladium-catalyzed cross-coupling with triorganoindium reagents were developed. The double cyclization is stereospecific and operates via a biomimetic cascade cation-olefin through 1,5-enyne cyclization (6-endo-dig) and subsequent C–C hydroarylation or C–O phenoxycyclization. Density functional theory (DFT) computational studies on 1,5-enynyl aryl ethers support a two-step mechanism where the first stereoselective 1,5-enyne cyclization produces a nonclassical carbocation intermediate that evolves to the tricyclic reaction product through a SᴇAr mechanism. Using this approach, a variety of tricyclic heterocycles such as benzo[b]chromenes, phenanthridines, xanthenes, and spiroheterocyclic compounds are efficiently synthesized with high atom economy.engAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/journal articleopen access