CAS 2770450-18-3, Cat. No EN300-51882349
Reagent for homologation and C–H functionalization
This O-alkenyl hydroxamate is a bench-stable, thermally activated amidyl-radical precursor used for highly site-selective C(sp³)–H functionalization1 and homologation of carboxylic acids2. The reagent is a key component in the novel radical-based reagent for the homologation of carboxylic acids via decarboxylative chain extension2. Upon mild heating, N–O bond homolysis generates a bulky tert-butyl amidyl radical that performs selective hydrogen-atom transfer (HAT) at predictable aliphatic positions, followed by efficient radical trapping in a chain process3. Broadly effective for unactivated alkanes, N-alkyl amines, bridged systems, cyclic and acyclic substrates, and late-stage functionalization of complex molecules (terpenoids, steroids, drug-like scaffolds)4. Enables C–H heteroarylation with heteroaryl sulfones and annulative C–H functionalization leading to indole and polycyclic heterocycle formation5. Exhibits high site selectivity in HAT (governed by sterics and electronics), excellent regioselectivity in downstream coupling, and good diastereocontrol in rigid substrates. Competing over-functionalization is minimized by the sterically demanding amidyl radical.
Synonyms: N-(1,1-dimethylethyl)-N-[(1-phenylethenyl)oxy]-3,5-bis(trifluoromethyl)benzamide, N-tert-butyl-N-[(1-phenylethenyl)oxy]-3,5-bis(trifluoromethyl)benzamide
Selected publication
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Divergent Concerted Proton–Electron Transfer (CPET) and Hydrogen Atom Transfer (HAT) Pathways of Amidyl Radical Reactivity Enable Chemoselective Functionalization.
Handlin, A. D.; Leibfarth, F. A.; Alexanian, E. J. Org. Lett. 2025, 27 (43), 12018–12023. DOI: 10.1021/acs.orglett.5c03705
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Homologation of Carboxylic Acids Using a Radical-Polar Conjunctive Reagent.
Gruhin, J. N.; Kim, R.; Vasilopoulos, A.; Voight, E. A.; Alexanian, E. J. J. Am. Chem. Soc. 2024. DOI: 10.1021/jacs.4c13687
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Heteroarylation of Unactivated C-H Bonds Suitable for Late-Stage Functionalization.
Miller, A. S.; Alexanian, E. J. Chem. Sci. 2024, 13 (40), 11878–11882. DOI: 10.1039/d2sc04605a
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Blocky Selective Postpolymerization C–H Functionalization of Polyolefins.
Neidhart, E. K.; Pomatto, M. E.; Vasallo, C.; Crater, E. R.; Alty, J. W.; Angelopoulou, P. P.; Alexanian, E. J.; Kearney, L. T.; Moore, R. B.; Leibfarth, F. A. Angew. Chem. Int. Ed. 2025, 64 (30). DOI: 10.1002/anie.202507687
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General Synthesis of N-Alkylindoles from N,N-Dialkylanilines via [4 + 1] Annulative Double C-H Functionalization.
Zhang, B.; Erb, F. R.; Vasilopoulos, A.; Voight, E. A.; Alexanian, E. J. J. Am. Chem. Soc. 2023, 145 (49), 26540–26544. DOI: 10.1021/jacs.3c10751