Zeoly, Lucas A.Acconcia, Lais V.Rodrigues, Jr., Manoel T.Santos, HugoCormanich, Rodrigo A.Paniagua, Juan CarlosMoyano i Baldoire, AlbertCoelho, Fernando2023-07-142023-07-142023-04-141477-0520https://hdl.handle.net/2445/200659Indolizines and their saturated derivatives are important structural motifs present in several biologically active compounds of both natural and synthetic origin. We describe herein a one-pot approach for the synthesis of tricyclic indolizines catalyzed by a bicyclic imidazole-alcohol. The protocol is based on an aqueous Morita-Baylis-Hillman reaction between pyridine-2-carboxaldehydes and six- or seven-membered cyclic enones, followed by sequential intramolecular cyclization and dehydration. So, in a single operational step two new bonds (C-C and C-N) are formed in an organocatalyzed process that takes place in simple conditions (stirring in water at 60 °C for 12 h) and with great atom economy (water as the sole byproduct), affording the purified compounds in yields ranging from 19 to 70%. The facility of the cyclization strongly depends on the size of the cycloalkenone ring: while MBH adducts derived from six-, seven- or eight-membered cycloenones are readily transformed into the corresponding indolizines, cyclopentenone-derived MBH adducts do not cyclize. A competition experiment revealed that cycloheptenone- derived MBH adducts cyclize faster than cyclohexenone-derived adducts. Model DFT calculations have been performed to rationalize these reactivity trends.15 p.application/pdfengcc-by (c) Zeoly, Lucas A. et al., 2023http://creativecommons.org/licenses/by/3.0/es/CatàlisiQuímica de l'aiguaIsomeritzacióCatalysisWater chemistryIsomerizationinfo:eu-repo/semantics/article7376542023-07-14info:eu-repo/semantics/openAccess