Chemical reactions are a vital process in the synthesis of products for a diversity of purposes. For the most part, these reactions are carried out in the liquid phase, by dissolving the reactants in a solvent. The starting materials required for the synthesis of many cutting-edge organic materials, such as organic semiconductors and luminescent materials, are often poorly soluble, leading to problems in solution-based synthesis. Therefore, the development of a solvent-independent synthetic approach to overcome these long-standing solubility issues in organic synthesis is highly desired to synthesize new valuable organic molecules.
Researchers from Hokkaido University have developed a rapid, efficient, solvent-free protocol for Suzuki-Miyaura cross-coupling reaction of insoluble aryl halides. Cross-coupling reactions have been employed for the synthesis of a wide range of valuable molecules, but insoluble aryl halides are not suitable substrates because Suzuki-Miyaura cross-coupling reactions have primarily been carried out in solution. Given this limitation, the research team focused on the development of an efficient solid-state Suzuki-Miyaura cross-coupling of numerous extremely unreactive insoluble aryl halides. The key equipment comprised a ball mill, for mixing reactants; a heat gun, to increase the temperature at which the reactions took place; and a catalytic system, composed of palladium acetate, SPhos, and 1,5-cyclooctadiene. The study was published in the Journal of the American Chemical Society.
"The high-temperature ball-milling technique and our catalytic system are essential for these cross-coupling reactions of insoluble aryl halides, and the protocol we have developed expands the diversity of organic molecules derived from insoluble starting materials," said associated professor and study co-author Koji Kubota.
Photo: Insoluble reactants are hardly reactive in solution but may react in solvent-free systems using ball milling to drive chemical reactions in the solid state. Credit: Tamae Seo, et al. Journal of the American Chemical Society. March 30, 2021.