{ "dc.contributor.author": "Call Quintana, Arnau" , "dc.contributor.author": "Cianfanelli, Marco" , "dc.contributor.author": "Besalú Sala, Pau" , "dc.contributor.author": "Olivo, Giorgio" , "dc.contributor.author": "Palone, Andrea" , "dc.contributor.author": "Vicens Serra, Laia" , "dc.contributor.author": "Ribas, Xavi" , "dc.contributor.author": "Luis Luis, Josep Maria" , "dc.contributor.author": "Bietti, Massimo" , "dc.contributor.author": "Costas Salgueiro, Miquel" , "dc.date.accessioned": "2022-11-07T13:45:33Z" , "dc.date.available": "2022-11-07T13:45:33Z" , "dc.date.issued": "2022-10-13" , "dc.identifier.issn": "0002-7863" , "dc.identifier.uri": "http://hdl.handle.net/10256/22010" , "dc.description.abstract": "Reactions that enable selective functionalization of strong aliphatic C-H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific C-H bond by catalyst control. Herein we describe the catalytic site- and stereoselective γ-lactonization of unactivated primary C-H bonds in carboxylic acid substrates. The system relies on a chiral Mn catalyst that activates aqueous hydrogen peroxide to promote intramolecular lactonization under mild conditions, via carboxylate binding to the metal center. The system exhibits high site-selectivity and enables the oxidation of unactivated primary γ-C-H bonds even in the presence of intrinsically weaker and a priori more reactive secondary and tertiary ones at α- and β-carbons. With substrates bearing nonequivalent γ-C-H bonds, the factors governing site-selectivity have been uncovered. Most remarkably, by manipulating the absolute chirality of the catalyst, γ-lactonization at methyl groups in gem-dimethyl structural units of rigid cyclic and bicyclic carboxylic acids can be achieved with unprecedented levels of diastereoselectivity. Such control has been successfully exploited in the late-stage lactonization of natural products such as camphoric, camphanic, ketopinic, and isoketopinic acids. DFT analysis points toward a rebound type mechanism initiated by intramolecular 1,7-HAT from a primary γ-C-H bond of the bound substrate to a highly reactive MnIV-oxyl intermediate, to deliver a carbon radical that rapidly lactonizes through carboxylate transfer. Intramolecular kinetic deuterium isotope effect and 18O labeling experiments provide strong support to this mechanistic picture" , "dc.description.sponsorship": "This work was supported by the Spanish Ministry of Science, Innovation, and Universities (PGC2018-101737-B-I00 to M.C., PGC2018-098212-B-C22 to J.M.L., IJC2020-046115-I to A.C.; and PhD grants FPU16/04231 to L.V., FPU17/02058 to P.B.-S., and PRE2019-090149 to A.P.), the University of Rome “Tor Vergata” (Project E84I20000250005), the European Research Council, (AdvG 883922 to M.C.), and Generalitat de Catalunya (ICREA Academia Award and 2017-SGR00264 to M.C. and X.R., and 2017SGR39 to J.M.L.)" , "dc.format.mimetype": "application/pdf" , "dc.language.iso": "eng" , "dc.publisher": "American Chemical Society (ACS)" , "dc.relation": "PGC2018-101737-B-I00" , "dc.relation": "PGC2018-098212-B-C22" , "dc.relation.isformatof": "Reproducció digital del document publicat a: https://doi.org/10.1021/jacs.2c08620" , "dc.relation.ispartof": "Journal of the American Chemical Society, 2022, vol.144, núm. 42, p. 19542-19558" , "dc.relation.ispartofseries": "Articles publicats (D-Q)" , "dc.rights": "Attribution 4.0 International" , "dc.rights.uri": "http://creativecommons.org/licenses/by/4.0/" , "dc.subject": "Catàlisi" , "dc.subject": "Catalysis" , "dc.subject": "Àcids carboxílics" , "dc.subject": "Carboxylic acids" , "dc.title": "Carboxylic Acid Directed γ-Lactonization of Unactivated Primary C-H Bonds Catalyzed by Mn Complexes: Application to Stereoselective Natural Product Diversification" , "dc.type": "info:eu-repo/semantics/article" , "dc.rights.accessRights": "info:eu-repo/semantics/openAccess" , "dc.relation.projectID": "info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-101737-B-I00/ES/CATALISIS DE OXIDACION BIOINSPIRADA MEDIANTE DISEÑO RACIONAL DE CATALIZADORES/" , "dc.relation.projectID": "info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-098212-B-C22/ES/DESCOMPOSICION EN EL ESPACIO REAL DE PROPIEDADES OPTICAS NO LINEALES PARA EL DISEÑO RACIONAL DE MATERIALES OPTOELECTRONICOS/" , "dc.relation.projectID": "info:eu-repo/grantAgreement/EC/H2020/883922/EU/Enantioselective C-H Oxidation Guided by Rational Catalyst Design/ECHO-GRACADE" , "dc.type.version": "info:eu-repo/semantics/publishedVersion" , "dc.identifier.doi": "https://doi.org/10.1021/jacs.2c08620" , "dc.identifier.idgrec": "036681" , "dc.contributor.funder": "Agencia Estatal de Investigación" , "dc.contributor.funder": "European Commission" , "dc.type.peerreviewed": "peer-reviewed" , "dc.relation.FundingProgramme": "Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020" , "dc.relation.FundingProgramme": "H2020" , "dc.relation.ProjectAcronym": "CATALISIS DE OXIDACION BIOINSPIRADA MEDIANTE DISEÑO RACIONAL DE CATALIZADORES" , "dc.relation.ProjectAcronym": "DESCOMPOSICION EN EL ESPACIO REAL DE PROPIEDADES OPTICAS NO LINEALES PARA EL DISEÑO RACIONAL DE MATERIALES OPTOELECTRONICOS" , "dc.relation.ProjectAcronym": "ECHO-GRACADE" , "dc.identifier.eissn": "1520-5126" }