Mechanistic Comparison between Pd-Catalyzed Ligand-Directed C−H Chlorination and C−H Acetoxylation

Abstract

This communication describes detailed investigations of the mechanism of the Pd-catalyzed C-H chlorination and acetoxylation of 2-ortho-tolylpyridine. Under the conditions examined, both reactions proceed via rate limiting cyclopalladation. However, substrate and catalyst order as well as Hammett data indicate that the intimate mechanism of cyclopalladation differs significantly between PdCl2-catalyzed chlorination and Pd(OAc)2-catalyzed acetoxylation.

Transition-metal-catalyzed acetoxylation of heterocycles: all that glitters is not palladium

“…Thus, electron-rich indoles readily underwent acetoxylation, whereas electron-deficient indoles required increased amounts of PhI(OAc) 2 (up to 2.5 equiv) and prolonged reaction times to achieve synthetically useful yields; (iii) the acetoxylation of C-2 or C-3 unsubstituted indoles occurred regioselectively at the C-3 position*. These observations together with the commonly accepted mechanism for Pd-catalyzed C-H activation/acetoxylation of benzene rings [5][6][7] led authors to propose that the first step of the catalytic cycle is electrophilic palladation of indole [2,3]. In fact, it has been demonstrated earlier that electrophilic metallation of indoles with Pd(II) species occurs regioselectively at the more electron-rich C-3 position rather than at C-2 [8].…”

The Halogenation of Aliphatic C-H Bonds with Peracetic Acid and Halide Salts

“…Proton and carbon 13 nuclear magnetic resonance ( 1 H NMR, 13 C NMR) spectra were collected on either a 400 MHz or a 250 MHz Bruker AV spectrometer. All NMR spectra were referenced to internal standards.…”

“…[12][13][14][15][16][17][18] Less advancement has been made in the development of mild reactions capable of halogenating aliphatic C-H bonds. 9,12,19 The procedure used most commonly in industry is free-radical halogenation, in which either Cl 2 or Br 2 serve as both terminal oxidant and halogen source.…”

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

“…Fluorination of arene C-H bonds with redoxactive transition metal catalysts can potentially proceed via direct C-H metalation, followed by oxidation of the metal center with an electrophilic fluorinating reagent. Depending on the reaction conditions, oxidation can result in the formation of a monometallic high-valent intermediate [115,168,169] or a high-valent multimetallic complex [117,118,165,170].…”