The study of calcium-based Grignard reagents (R-CaX) has historically been limited due to the challenges in their synthesis. However, calcium’s biocompatibility and distinct chemical properties make it a highly promising candidate for organic synthesis applications. Unlike their magnesium-based counterparts (R-MgX), calcium-based reagents exhibit stronger polarity and a higher degree of ionic character in the carbon-metal bond. This increased ionic nature can result in unique reactivity, offering advantages in specific transformations where magnesium-based reagents may be less effective. Traditional methods for synthesizing calcium-based Grignard reagents are cumbersome, requiring the pre-activation of metallic calcium through processes involving toxic materials such as liquid ammonia or highly reactive lithium. These harsh conditions not only present safety concerns but also limit the reagents' practicality, particularly in industrial applications where scalability and safety are crucial. In recent years, mechanochemistry has emerged as a sustainable alternative to conventional methods, providing opportunities to improve reaction efficiency and reduce the use of solvents. The mechanical energy generated by ball milling has been shown to disrupt the inert surface layer of metallic calcium, allowing for in situ activation. This enables the calcium to react with organohalides, forming calcium-based Grignard reagents without the need for toxic reagents or complex pre-activation steps. Once formed, these reagents can act as carbon nucleophiles, reacting with pinacolborane (HBpin) to form organoboron compounds, which are valuable intermediates in organic synthesis. This study demonstrates that by utilizing the continuous mechanical energy of ball milling, a variety of boronated products can be synthesized efficiently and with high yields. The method also shows broad substrate compatibility, particularly excelling in reactions involving poorly soluble aryl bromides, where traditional solution-based systems often fail. In conclusion, this work marks the first successful application of calcium-based Grignard reagents in borylation reactions via mechanochemical methods, offering a novel and efficient approach that addresses the limitations of conventional techniques.

Key words: Calcium-based heavy Grignard reagents, mechanochemistry, borylation reaction, green chemistry, solvent-free