摘要：Otome E. Okoromoba,[a]Ting-An Chen,[a,b]Eun Sil Jang,[a]Claire L. McMullin,[c]Thomas R. Cundari,[d]*and Timothy H. Warren[a,b]*

转自：康龙化成

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

Otome E. Okoromoba,[a] Ting-An Chen,[a,b] Eun Sil Jang,[a] Claire L. McMullin,[c] Thomas R. Cundari,[d]* and Timothy H. Warren[a,b]*

Department of Chemistry, Georgetown University Box571227, Washington, DC 20057-1227 (USA)

Department of Chemistry, Michigan StateUniversity 578 S. Shaw Lane, East Lansing, MI 48824 (USA)

Department of Chemistry, University ofBath Bath, BA27AY (UK)

Department of Chemistry, Center forAdvanced Scientific Computing and Modeling (CASCaM), University of North Texas

—Angew. Chem. Int. Ed., 2024, DOI: 10.1002/anie.202418692

Recommended by Yuquan Liu_PT

KEYWORDS:Copper catalysis, a-acetylation (反应类型),C(sp3)-C(sp3)(成键类型),arylmethyl ketones (原料), α- alkylated ketones (产物), QuaternaryCenters (其他)

ABSTRACT: a-substitutedketones are important chemical targets as synthetic intermediates as well asfunctionalities in natural products and pharmaceuticals. We report thea-acetylation of C(sp3)-H substrates R-H with arylmethylketones ArC(O)Meto provide α- alkylated ketones ArC(O)CH2R at RT with tBuOOtBu asoxidant via copper(I) 𝛽-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituentswithout competing elimination that occurs in more traditional alkylationreactions between enolates and alkyl electrophiles. DFT studies

suggestthe intermediacy of copper(II) enolates [CuII](CH2C(O)Ar)that capture alkyl radicals R• to give R-CH2C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH2CH2C(O)Ar.

Catalytic sp3 C-H acetylation with acetophenone

C-Hacetylation of ketones with ethylbenzene

Quaternary carbon formation via sp3C-H acetylation

Proposed mechanism: Catalytic C-Hfunctionalization via radical relay

Summary and Comments

Prof. Thomas R. Cundariet al havedeveloped anovel intermolecular copper catalyzed sp3 C-H a-acetylation for the construction of C-C bonds via copper catalyzed C-Hfunctionalization of benzylic and allylic substrates with acetophenones. Thisapproach that features readily available sp3 C-H substrates and alkyl aryl ketones, as well as acetoneoffers a complementary catalytic Csp3−Csp3 disconnection strategy to prepare smallmolecules that may be building blocks for the assembly of biologically activeand/or other synthetically useful products.

来源：新浪财经