More cross-coupling with less metal

Cross-coupling has been one of the most popular types of reactions in organic chemistry for decades. The pharma and agrochemical industries use these methods on a large scale to forge bonds between aromatic rings. One downside of these classic reactions is that they require one of the coupling partners to be fitted with an organometallic group before the coupling step. Methods that let chemists bypass that premetalation step in favor of directly stitching together two aryl halides have been gaining momentum. Such methods could shorten syntheses and cut waste. But they often still require a reductant such as zinc or manganese for the catalytic cycle to work, which can pose safety problems on scale-up. “These are useful reactions at the discovery level, but they’re a little challenging to deploy on scale” because metal reductants can plate onto reactors and cause a fire hazard, says Michael J. Krische of the University