Aqueous Route Eases Synthesis

Sept. 10, 2014
Next step: Broaden the scope of such reactions and increase the efficiency.

Researchers at McGill University, Montreal, have discovered a simple water-based route for direct metal-mediated arylation of aldehydes. Chao-Jun Li, Canada Research Chair in Green Chemistry, and Feng Zhou, a postdoctoral fellow in the school’s department of chemistry, say their route avoids challenges posed by conventional two-step organic-solvent-based synthesis, such as the need to exclude air and moisture. “It thereby creates a safer, more convenient and more environmentally benign strategy to access the diarylmethanols and aryl alkyl alcohols, ubiquitous skeletons found in fine chemicals, biologically active molecules, and pharmaceuticals,” they note.


Figure 1. Feng Zhou of McGill University co-discovered water-based route. Source: Haining Wang.

The researchers claim they are the first to succeed in a direct Barbier-Grignard-type arylation of aldehydes with simple unactivated aryl iodides in water. They used a rhodium catalyst together with zinc as a mediator, and achieved yields of 75% under optimized conditions. More details appear in a recent article in Nature Communications. The key point of that paper is not the yields that were achieved but the creation of a synthesis route not possible via classical chemistry, says Zhou.“The next step is to broaden the scope of such reactions, increase the efficiency, and functionalize naturally occurring substrates and biological compounds such as sugar directly. This may take years to complete as new catalysts might be required,” he adds.“The key challenge remaining to be addressed is to further improve the yield, achieve asymmetric synthesis, as well as broaden the substrate scope,” notes Zhou.At this point, the researchers have no plans for trying the reaction on a pilot-plant scale. However, they might do such piloting if there’s a specific industrial need for a particular product.