Mechanochemical C–H bond activation: rapid and regioselective double cyclopalladation monitored by in situ Raman spectroscopy

Abstract

COMMUNICATIONThe first direct mechanochemical transition-metal-mediated activation of strong phenyl C-H bonds is reported. Mechanochemical procedure, resulting in cyclopalladated complexes, is quantitative and significantly faster than solution synthesis and allows highly regioselective activation of two C-H bonds by palladium(II) acetate in asymmetrically substituted azobenzene. Milling is monitored by in situ solidstate Raman spectroscopy and in combination with quantumchemical calculations enabled characterization of involved reaction species, direct insight into the dynamics and reaction pathways, as well as the optimization of a milling process.Cyclometalation via the transition-metal-mediated activation of carbon-hydrogen (C-H) bond is the simplest and the most common method for the formation of a metal-carbon (M-C) σ bond. 1 After the first reports in the middle 1960s, 2 the C-H activation process remains the most straightforward method for preparation of cyclometalated compounds which are widely used in organic synthetic chemistry for the insertion of various functionalities into hydrocarbons. 3 Among them, cyclopalladated compounds have been studied most extensively not only for their wide application in organic synthesis and catalysis, but also due to their mesogenic, bioactive and photoluminescent properties. 1a,1c,4 The synthesis of all known metalacycles relies exclusively on solvent-based techniques which may require elevated temperatures, toxic solvents (benzene, toluene, chloroform) and are often time-consuming. 1a,1c,4 During the last decade mechanochemical reactions emerged as a viable and environmentally-friendly alternative to solvent-based techniques. 5 Apart from the processing of inorganic materials, 6 mechanosynthesis has been recognized as a rapid, selective and atom-and energy-efficient pathway to various classes of compounds Ruđer Bošković Institute, Bijenička 54, HR-10000 Zagreb, Croatia E-mail: curic@irb.hr †Electronic Supplementary Information (ESI) available: Experimental and computational details. CCDC 1005635-1005636 For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc04423a ‡ These authors contributed equally to this work.ranging from organic molecules 7 and cocrystals 8 up to metal-organic coordination compounds. 9 Despite its wide application in different areas of chemistry, solid-state synthesis of organometallic compounds by direct formation of a M-C σ bond has not been reported yet.Here we describe the first example of palladium-mediated solidstate C-H bond activation in asymmetrically substituted azobenzene 1, achieved by mechanochemical milling process (Scheme 1). The palladation of 1 proved to be regioselective, producing regioisomer 1A in higher yield and much faster than the analogous reaction in solution, with the reduction of solvent volume more than 10000 times. Further reaction of 1A with palladium(II) acetate (Pd(OAc) 2 ) leads to the second C-H bond activation forming in a quantitative yield the doubly palladated complex 1...

Mechanism of Mechanochemical C−H Bond Activation in an Azobenzene Substrate by PdII Catalysts

“…The ball‐milling procedures proved more advantageous than solution techniques due to much shorter reaction times and achievement of double C−H bond activation, producing dipalladated compounds not available from solution. Therein, in situ Raman monitoring has shown that palladation of azobenzene by [Pd(OAc) 2 ] 3 occurs regioselectively, first on the phenyl ring with the electron‐donating substituent …”

Mechanochemically Activated Oxidative Coupling of Indoles with Acrylates through C–H Activation: Synthesis of 3-Vinylindoles and β,β-Diindolyl Propionates and Study of the Mechanism

“…Firstly, several oxidants were tested, and the yield were elevated to 61% by using MnO 2 ( Table 1, entries [1][2][3][4][5].…”

“…Continuously, another two Figure 2b). Similar homo-coupling product appeared again, and was supposed as the reductive elimination product from [Pd 2 (1a-H) 3 OAc] + (m/z at 662.6). Additionally, samples without LAG were examined carefully, implicating the reaction underwent similar pathway.…”

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp2 C–H bond activation in ball mills

“…A few mechanochemical ortho -C–H bond activation reactions under the catalysis of rhodium and palladium salts have been reported [29–38]. Hernández and Bolm reported the rhodium-catalyzed bromination and iodination of 2-phenylpyridine using N -bromosuccinimide (NBS) and N -iodosuccinimide (NIS), respectively, as the halogen source [30].…”