Palladium-Catalyzed meta-C–H Allylation of Arenes: A Unique Combination of a Pyrimidine-Based Template and Hexafluoroisopropanol

• Published in: Journal of the American Chemical Society Vol. 142; no. 28; pp. 12453 - 12466
• Main Authors: Bag, Sukdev, K, Surya, Mondal, Arup, Jayarajan, Ramasamy, Dutta, Uttam, Porey, Sandip, Sunoj, Raghavan B, Maiti, Debabrata
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.07.2020; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; REARRANGEMENT; LIGAND; MECHANISM; MOLECULAR-ORBITAL THEORY; BOND FUNCTIONALIZATIONS; ACTIVATION STRAIN MODEL
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c05223

Controlling remote selectivity and delivering novel functionalities at distal positions in arenes are an important endeavor in contemporary organic synthesis. In this vein, template engineering and mechanistic understanding of new functionalization strategies are essential for enhancing the scope of such methods. Herein, meta-C–H allylation of arenes has been achieved with the aid of a palladium catalyst, pyrimidine-based auxiliary, and allyl phosphate. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) was found as a critical solvent in this transformation. The role of HFIP throughout the catalytic cycle has been systematically studied. A broad substrate scope with phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl ester, phenylacetic acid, hydrocinnamic acid, and 2-phenylbenzoic acid derivatives has been demonstrated. Interestingly, conformationally flexible arenes have also been selectively allylated at the meta-position using allyl phosphate. A combination of 1H NMR, 31P NMR, ESI-MS, kinetic experiments, and density functional theory (DFT) computations suggested that reaction proceeds through a ligand-assisted meta-C–H activation, allyl addition forming a Pd-π-allyl complex which is then followed by a turnover determining the C–C bond formation step leading to the meta-allylated product.