Copper-Catalyzed C(sp3)-H α-Acetylation: Generation of Quaternary Centers

被引：2

作者：

Okoromoba, Otome E. ^{[1
]}

Chen, Ting-An ^{[1
,2
]}

Jang, Eun Sil ^{[1
]}

McMullin, Claire L. ^{[3
]}

Cundari, Thomas R. ^{[4
]}

Warren, Timothy H. ^{[1
,2
]}

机构：

[1] Georgetown Univ, Dept Chem, Box 571227, Washington, DC 20057 USA

[2] Michigan State Univ, Dept Chem, 578 S Shaw Lane, E Lansing, MI 48824 USA

[3] Univ Bath, Dept Chem, Bath BA27AY, Avon, England

[4] Univ North Texas, Dept Chem, Ctr Adv Sci Comp & Modeling CASCaM, Denton, TX 76203 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2025年 / 64卷 / 05期

关键词：

Acetylation; Copper; Ketones; C-H Functionalization; Catalysis; C-C BOND; TRANSITION-METAL; ALKYLATION; KETONES; ALCOHOLS; OLEFINS; CARBON;

D O I：

10.1002/anie.202418692

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

a-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the a-acetylation of C(sp(3)) H substrates R H with arylmethyl ketones ArC(O)Me to provide aalkylated ketones ArC(O)CH2R at RT with (BuOOBu)-Bu-t-Bu-t as oxidant via copper(I) beta-diketiminato catalysts. Proceeding via alkyl radicals R center dot, this method enables asubstitution 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.

引用

页数：5

共 38 条

[1] Copper catalyzed allylic oxidation with peresters [J].

Andrus, MB ;

Lashley, JC .

TETRAHEDRON, 2002, 58 (05) :845-866

[2] Revisiting the Synthesis and Nucleophilic Reactivity of an Anionic Copper Superoxide Complex [J].

Bailey, Wilson D. ;

Gagnon, Nicole L. ;

Elwell, Courtney E. ;

Cramblit, Anna C. ;

Bouchey, Caitlin J. ;

Tolman, William B. .

INORGANIC CHEMISTRY, 2019, 58 (08) :4706-4711

[3] Three-Coordinate Copper(II) Alkynyl Complex in C-C Bond Formation: The Sesquicentennial of the Glaser Coupling [J].

Bakhoda, Abolghasem ;

Okoromoba, Otome E. ;

Greene, Christine ;

Boroujeni, Mandi Raghibi ;

Bertke, Jeffery A. ;

Warren, Timothy H. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2020, 142 (43) :18483-18490

[4] ALKYLATION OF ENOLATES WITH TRIFLATES [J].

BATES, RB ;

TAYLOR, SR .

JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (16) :4469-4470

[5] Copper-catalyzed oxidative coupling of benzylic C-H bonds with 1,3-dicarbonyl compounds [J].

Borduas, Nadine ;

Powell, David A. .

JOURNAL OF ORGANIC CHEMISTRY, 2008, 73 (19) :7822-7825

[6] Palladium-catalyzed addition of ketones to alkylidenecyclopropanes [J].

Camacho, DH ;

Nakamura, I ;

Oh, BH ;

Saito, S ;

Yamamoto, Y .

TETRAHEDRON LETTERS, 2002, 43 (16) :2903-2907

[7] Copper catalyzed benzylic sp3 C-H alkenylation [J].

Chen, Ting-An ;

Staples, Richard J. ;

Warren, Timothy H. .

CHEMICAL SCIENCE, 2024, 15 (42) :17685-17690

[8] Ruthenium-catalyzed regioselective α-alkylation of ketones with primary alcohols [J].

Cho, CS ;

Kim, BT ;

Kim, TJ ;

Shim, SC .

TETRAHEDRON LETTERS, 2002, 43 (44) :7987-7989

[9] Catalytic asymmetric synthesis of all-carbon quaternary stereocenters [J].

Douglas, CJ ;

Overman, LE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (15) :5363-5367

[10] Copper-Catalyzed C(sp3)-H Methylation via Radical Relay [J].

Figula, Bryan C. ;

Chen, Ting-An ;

Bertke, Jeffery A. ;

Warren, Timothy H. .

ACS CATALYSIS, 2022, 12 (19) :11854-11859

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