The pyridyldiisopropylsilyl group: A masked functionality and directing group for monoselective ortho-Acyloxylation and ortho-Halogenation reactions of arenes

Chunhui Huang, Natalia Chernyak, Alexander S. Dudnik, Vladimir Gevorgyan

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Abstract

A novel, easily removable and modifiable silicon-tethered pyridyldiisopropylsilyl directing group for C-H functionalizations of arenes has been developed. The installation of the pyridyldiisopropylsilyl group can efficiently be achieved via two complementary routes using easily available 2-(diisopropylsilyl)pyridine (5). The first strategy features a nucleophilic hydride substitution at the silicon atom in 5 with aryllithium reagents generated in situ from the corresponding aryl bromides or iodides. The second milder route exploits a highly efficient room-temperature rhodium(I)-catalyzed cross-coupling reaction between 5 and aryl iodides. The latter approach can be applied to the preparation of a wide range of pyridyldiisopropylsilyl- substituted arenes possessing a variety of functional groups, including those incompatible with organometallic reagents. The pyridyldiisopropylsilyl directing group allows for a highly efficient, regioselective palladium(II)-catalyzed mono-ortho-acyloxylation and ortho-halogenation of various aromatic compounds. Most importantly, the silicon-tethered directing group in both acyloxylated and halogenated products can easily be removed or efficiently converted into an array of other valuable functionalities. These transformations include protio-, deuterio-, halo-, boro-, and alkynyldesilylations, as well as a conversion of the directing group into the hydroxy functionality. In addition, the construction of aryl-aryl bonds via the Hiyama-Denmark cross-coupling reaction is feasible for the acetoxylated products. Moreover, the ortho-halogenated pyridyldiisopropylsilylarenes, bearing both nucleophilic pyridyldiisopropylsilyl and electrophilic aryl halide moieties, represent synthetically attractive 1,2-ambiphiles. A unique reactivity of these ambiphiles has been demonstrated in efficient syntheses of arylenediyne and benzosilole derivatives, as well as in a facile generation of benzyne. In addition, preliminary mechanistic studies of the acyloxylation and halogenation reactions have been performed. A trinuclear palladacycle intermediate has been isolated from a stoichiometric reaction between diisopropyl(phenyl)pyrid-2-ylsilane (3a) and palladium acetate. Furthermore, both C-H functionalization reactions exhibited equally high values of the intramolecular primary kinetic isotope effect (kH/k D=6.7). Based on these observations, a general mechanism involving the formation of a palladacycle via a C-H activation process as the rate-determining step has been proposed.

Original languageEnglish (US)
Pages (from-to)1285-1305
Number of pages21
JournalAdvanced Synthesis and Catalysis
Volume353
Issue number8
DOIs
StatePublished - May 1 2011

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Keywords

  • C-H activation
  • acyloxylation
  • catalysis
  • halogenation
  • palladium
  • silicon

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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