tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C-H Bonds.

Autor: Chan SC; Institut de Química Computacional i Catàlisi (IQCC), Departament de Química, Universitat de Girona, Campus Montilivi, Girona, E-17071, Catalonia, Spain., Palone A; Institut de Química Computacional i Catàlisi (IQCC), Departament de Química, Universitat de Girona, Campus Montilivi, Girona, E-17071, Catalonia, Spain., Bietti M; Dipartimento di Scienze e Tecnologie Chimiche, Università 'Tor Vergata'; Via della Ricerca Scientifica, 1, I-00133, Rome, Italy., Costas M; Institut de Química Computacional i Catàlisi (IQCC), Departament de Química, Universitat de Girona, Campus Montilivi, Girona, E-17071, Catalonia, Spain.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Jul 08; Vol. 63 (28), pp. e202402858. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1002/anie.202402858
Abstrakt: 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( CF3 bpeb)(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.
(© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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