2026-04-13T05:42:15Zhttps://recercat.cat/oai/request
oai:recercat.cat:10256/250822026-02-24T07:11:29Zcom_2072_452955com_2072_2054col_2072_453073
RECERCAT author Chan, Siu-Chung author Palone, Andrea author Bietti, Massimo author Costas Salgueiro, Miquel 2024-07-08 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 architecturesEconomic 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 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Catàlisi homogènia Homogeneous catalysis Catalitzadors de manganès Manganese catalysts Grups funcionals Functional groups tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C−H Bonds info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed