2026-04-18T04:29:06Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/250822026-02-24T07:11:29Zcom_2072_452955com_2072_2054col_2072_453073

tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C−H Bonds Chan, Siu-Chung Palone, Andrea Bietti, Massimo Costas Salgueiro, Miquel European Commission Agencia Estatal de Investigación Catàlisi homogènia Homogeneous catalysis Catalitzadors de manganès Manganese catalysts Grups funcionals Functional groups The tert-butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol−1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert-butyl C−H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro-tert-butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese-oxo species that effectively oxidizes tert-butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site-selective and product chemoselective hydroxylation of the tert-butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late-stage hydroxylation at tert-butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert-butyl as a potential functional group in strategic synthetic planning for complex molecular architectures Economic support from European Research Council, (AdvG 883922 to M. C.) Spain Ministry of Science, (MINECO, PID2021-129036NB-I00 to M. C.), (MINECO, PRE2019-090149 to A. P.). Generalitat de Catalunya, (2021 SGR 00475) Open Access funding provided thanks to the CRUE-CSIC agreement with Wiley 2024-07-08 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed http://hdl.handle.net/10256/25082 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/anie.202402858 info:eu-repo/semantics/altIdentifier/issn/1433-7851 info:eu-repo/semantics/altIdentifier/eissn/1521-3773 PID2021-129036NB-I00 info:eu-repo/grantAgreement/EC/H2020/883922/EU/Enantioselective C-H Oxidation Guided by Rational Catalyst Design/ECHO-GRACADE info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-129036NB-I00/ES/CATALIZADORES MOLECULARES BIOINSPIRADOS PARA LA FUNCIONALIZACION ESTEREOSELECTIVA DE ENLACES SP2 Y SP3 C-H/ Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Wiley Angewandte Chemie International Edition, 2024, vol. 63, núm. 28, p. e202402858 Articles publicats (D-Q)