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Palladium-Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand-Assisted Halide Exchange.

ABSTRACT: We report an efficient and broadly applicable palladium-catalyzed iodination of inexpensive and abundant aryl and vinyl carboxylic acids via in situ activation to the acid chloride and formation of a phosphonium salt. The use of 1-iodobutane as iodide source in combination with a base and a deoxychlorinating reagent gives access to a wide range of aryl and vinyl iodides under Pd/Xantphos catalysis, including complex drug-like scaffolds. Stoichiometric experiments and kinetic analysis suggest a unique mechanism involving C-P reductive elimination to form the Xantphos phosphonium chloride, which subsequently initiates an unusual halogen exchange by outer sphere nucleophilic substitution.

SUBMITTER: Boehm P

PROVIDER: S-EPMC8362116 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Palladium-Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand-Assisted Halide Exchange.

Boehm Philip P Martini Tristano T Lee Yong Ho YH Cacherat Bastien B Morandi Bill B

Angewandte Chemie (International ed. in English) 20210626 31

We report an efficient and broadly applicable palladium-catalyzed iodination of inexpensive and abundant aryl and vinyl carboxylic acids via in situ activation to the acid chloride and formation of a phosphonium salt. The use of 1-iodobutane as iodide source in combination with a base and a deoxychlorinating reagent gives access to a wide range of aryl and vinyl iodides under Pd/Xantphos catalysis, including complex drug-like scaffolds. Stoichiometric experiments and kinetic analysis suggest a u ...[more]

PMID: 34013616

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