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Abstract α‐substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the α‐acetylation of C(sp3)−H substrates R−H with arylmethyl ketones ArC(O)Me to provide α‐alkylated ketones ArC(O)CH2R at RT withtBuOOtBu as oxidant via copper(I) ‐diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α‐substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [CuII](CH2C(O)Ar) that capture alkyl radicals R• to give R−CH2C(O)Ar outcompeting dimerization of the copper(II) enolate to give the 1,4‐diketone ArC(O)CH2CH2C(O)Ar.
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Copper‐Catalyzed C(sp 3 )−H Amidation: Sterically Driven Primary and Secondary C−H Site‐Selectivity
Abstract Undirected C(sp3)−H functionalization reactions often follow site‐selectivity patterns that mirror the corresponding C−H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C−H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C−H bonds over tertiary and benzylic C−H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C−H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N3. Mechanistic and DFT studies indicate that C−H amidation involves H‐atom abstraction from R‐H substrates by nitrene intermediates [Cu](κ2‐N,O‐NC(O)Ar) to provide carbon‐based radicals R.and copper(II)amide intermediates [CuII]‐NHC(O)Ar that subsequently capture radicals R.to form products R‐NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C−H amidation selectivity in the absence of directing groups.
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- Award ID(s):
- 1665348
- PAR ID:
- 10085418
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 58
- Issue:
- 11
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 3421-3425
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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