Pd couples together pairs of C–H bonds

Using a commonly available oxidant and making water as the only by-product, chemists at Scripps Research have figured out a way to take pairs of carbon-hydrogen bonds and directly couple them to make carbon-carbon bonds. With a palladium catalyst and sodium percarbonate, Jin-Quan Yu and coworkers brought together aryl and aliphatic carboxylic acids to make a variety of compounds commonly used in pharmaceuticals (ChemRxiv 2020, DOI: 10.26434/chemrxiv.13250294.v1). The study has not been peer-reviewed. To show how well the reaction works, the researchers used it to shorten the total synthesis of (±)-russujaponol F from 13 to 4 steps in 28% overall yield, using readily available starting materials (shown). “So basically we have four C–H bonds coupled together in one pot, to make a structured natural product,” Yu says. The oxidant forms H₂O₂ in solution, which industrial chemists already use, making this reaction potentially scalable, he says. Aliphatic carboxylic acids are readily available and usually cheap, and they can stand in as a preinstalled directing group for the reaction. The yields ranged from 52 to 78% for more reactive compounds and from 35 to 65% for less-reactive starting materials.