000131685 001__ 131685
000131685 005__ 20241125101139.0
000131685 0247_ $$2doi$$a10.1021/jacs.3c10863
000131685 0248_ $$2sideral$$a137106
000131685 037__ $$aART-2023-137106
000131685 041__ $$aeng
000131685 100__ $$aMatador, Esteban
000131685 245__ $$aA Photochemical Strategy for the Conversion of Nitroarenes into Rigidified Pyrrolidine Analogues
000131685 260__ $$c2023
000131685 5203_ $$aBicyclic amines are important motifs for the preparation of bioactive materials. These species have well-defined exit vectors that enable accurate disposition of substituents toward specific areas of chemical space. Of all possible skeletons, the 2-azabicyclo[3.2.0]heptane framework is virtually absent from MedChem libraries due to a paucity of synthetic methods for its preparation. Here, we report a modular synthetic strategy that utilizes nitroarenes as flat and easy-to-functionalize feedstocks for the assembly of these sp3-rich materials. Mechanistically, this approach exploits two concomitant photochemical processes that sequentially ring-expand the nitroarene into an azepine and then fold it into a rigid bicycle pyrroline by means of singlet nitrene-mediated nitrogen insertion and excited-state-4π electrocyclization. A following hydrogenolysis provides, with full diastereocontrol, the desired bicyclic amine derivatives whereby the aromatic substitution pattern has been translated into the one of the three-dimensional heterocycle. These molecules can be considered rigid pyrrolidine analogues with a well-defined orientation of their substituents. Furthermore, unsupervised clustering of an expansive virtual database of saturated N-heterocycles revealed these derivatives as effective isosteres of rigidified piperidines. Overall, this platform enables the conversion of nitroarene feedstocks into complex sp3-rich heterocycles of potential interest to drug development.
000131685 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000131685 590__ $$a14.5$$b2023
000131685 592__ $$a5.489$$b2023
000131685 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b18 / 231 = 0.078$$c2023$$dQ1$$eT1
000131685 593__ $$aBiochemistry$$c2023$$dQ1
000131685 593__ $$aColloid and Surface Chemistry$$c2023$$dQ1
000131685 593__ $$aChemistry (miscellaneous)$$c2023$$dQ1
000131685 593__ $$aCatalysis$$c2023$$dQ1
000131685 594__ $$a24.4$$b2023
000131685 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131685 700__ $$aTilby, Michael J.
000131685 700__ $$aSaridakis, Iakovos
000131685 700__ $$0(orcid)0000-0003-4249-6748$$aPedrón, Manuel$$uUniversidad de Zaragoza
000131685 700__ $$aTomczak, Dawid
000131685 700__ $$aLlaveria, Josep
000131685 700__ $$aAtodiresei, Iuliana
000131685 700__ $$0(orcid)0000-0002-2202-3460$$aMerino, Pedro$$uUniversidad de Zaragoza
000131685 700__ $$aRuffoni, Alessandro
000131685 700__ $$aLeonori, Daniele
000131685 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000131685 773__ $$g145, 50 (2023), 27810-27820$$pJ. Am. Chem. Soc.$$tJournal of the American Chemical Society$$x0002-7863
000131685 8564_ $$s5437372$$uhttps://zaguan.unizar.es/record/131685/files/texto_completo.pdf$$yVersión publicada
000131685 8564_ $$s3066497$$uhttps://zaguan.unizar.es/record/131685/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131685 909CO $$ooai:zaguan.unizar.es:131685$$particulos$$pdriver
000131685 951__ $$a2024-11-22-12:01:56
000131685 980__ $$aARTICLE