Development and Mechanistic Investigations of a Base-Free Suzuki-Miyaura Cross-Coupling of α,α-Difluoroacetamides via C-N Bond Cleavage

被引:33
|
作者
Reina, Antonio [1 ]
Krachko, Tetiana [1 ]
Onida, Killian [1 ]
Bouyssi, Didier [1 ]
Jeanneau, Erwann [3 ]
Monteiro, Nuno [1 ]
Amgoune, Abderrahmane [1 ,2 ]
机构
[1] Univ Lyon 1, CNRS, UMR 5246, Inst Chim & Biochim Mol & Supramol, F-69100 Villeurbanne, France
[2] IUF, F-75005 Paris, France
[3] Univ Lyon 1, Ctr Diffractometrie Henri Longchambon, F-69100 Villeurbanne, France
关键词
cross-coupling; palladium catalysis; mechanism; transmetallation; synthetic method; difluoroketone; BORONIC ACIDS; ALPHA-ARYLATION; PALLADIUM; AMIDES; FLUORINE; ARYL; COMPLEXES; PHARMACEUTICALS; DISCOVERY; BROMIDES;
D O I
10.1021/acscatal.9b05159
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
This study describes the development and understanding of a palladium-catalyzed cross-coupling of fluoroacetamides with boronic acids, under base-free conditions, to selectively give valuable alpha,alpha-difluoroketone derivatives. Detailed mechanistic studies were conducted to assess the feasibility of each elementary step, that is, C(acyl)-N bond oxidative addition, followed by base free transmetallation and reductive elimination. These investigations allowed the structural characterization of palladium(II)-fluoroacyl intermediates derived from C-N bond oxidative addition of an amide electrophile. They also revealed the high reactivity of these intermediates for transmetallation with boronic acids without exogenous base. The mechanistic studies also provided a platform to design a practical catalytic protocol for the synthesis of a diversity of alpha,alpha-difluoroketones, including CF2H-ketones. Finally, the synthetic potential of this fluoroacylation methodology is highlighted in sequential, orthogonal C-Br and C-N bond functionalization of an alpha-bromo-alpha,alpha-difluoroacetamide with a focus on compounds of potential biological relevance.
引用
收藏
页码:2189 / 2197
页数:17
相关论文
共 50 条
  • [31] Computational characterization of the role of the base in the Suzuki-Miyaura cross-coupling reaction
    Braga, AAC
    Morgon, NH
    Ujaque, G
    Maseras, F
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (25) : 9298 - 9307
  • [32] Density Functional Theory Mechanistic Insight into the Base-Free Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Acid Fluoride: Concerted versus Stepwise Transmetalation
    Zhang, Chaoshen
    Zhao, Ruihua
    Dagnaw, Wasihun Menberu
    Liu, Zheyuan
    Lu, Yu
    Wang, Zhi-Xiang
    JOURNAL OF ORGANIC CHEMISTRY, 2019, 84 (21): : 13983 - 13991
  • [33] Mechanistic Aspects of the Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction
    D'Alterio, Massimo C.
    Casals-Cruanas, Eric
    Tzouras, Nikolaos V.
    Talarico, Giovanni
    Nolan, Steven P.
    Poater, Albert
    CHEMISTRY-A EUROPEAN JOURNAL, 2021, 27 (54) : 13481 - 13493
  • [34] Suzuki-Miyaura Cross-Coupling under Solvent-Free Conditions
    Asachenko, Andrey F.
    Sorochkina, Kristina R.
    Dzhevakov, Pavel B.
    Topchiy, Maxim A.
    Nechaev, Mikhail S.
    ADVANCED SYNTHESIS & CATALYSIS, 2013, 355 (18) : 3553 - 3557
  • [35] Recent Development of Constructing Porphyrin Arrays via Suzuki-Miyaura Cross-Coupling Reaction
    Chen Maolong
    Yin Bangshao
    Song Jianxin
    PROGRESS IN CHEMISTRY, 2015, 27 (06) : 641 - 654
  • [36] Palladium-free Suzuki-Miyaura cross-coupling at elevated pressures
    Guo, Yanhe
    Young, David J.
    Hor, T. S. Andy
    TETRAHEDRON LETTERS, 2008, 49 (39) : 5620 - 5621
  • [37] Postsynthetic Modification of Peptoids via the Suzuki-Miyaura Cross-Coupling Reaction
    Nam, Ho Yeon
    Seo, Jiwon
    BIOPOLYMERS, 2016, 106 (01) : 82 - 88
  • [38] Synthesis of 5-arylhistidines via a Suzuki-Miyaura cross-coupling
    Cerezo, Vanessa
    Afonso, Ana
    Planas, Marta
    Feliu, Lidia
    TETRAHEDRON, 2007, 63 (42) : 10445 - 10453
  • [39] Facile Synthesis of Phenanthridinone Alkaloids via Suzuki-Miyaura Cross-coupling
    Kuwata, Yoshiyuki
    Sonoda, Motohiro
    Tanimori, Shinji
    JOURNAL OF HETEROCYCLIC CHEMISTRY, 2017, 54 (02) : 1645 - 1651
  • [40] N-heterocyclic carbene palladium(II)-catalyzed Suzuki-Miyaura cross coupling of N-acylsuccinimides by C-N cleavage
    Wang, Tao
    Guo, Jiarui
    Wang, Hengjin
    Guo, Han
    Jia, Dingli
    Zhang, Wen
    Liu, Lantao
    JOURNAL OF ORGANOMETALLIC CHEMISTRY, 2018, 877 : 80 - 84