Coaxing Saturated Aldehydes And Ketones To React In An Unexpected Manner

When chemists pick out reactive hot spots on aldehydes and ketones, they generally focus on the electrophilic carbonyl carbon or the α-carbon next door. The α-carbon can easily shed a proton and become nucleophilic thanks to its relationship with the carbonyl. Such neighborliness doesn’t typically extend to the β-carbon just one atom further along, which generally is regarded as being too unreactive in saturated systems. To do anything at the β-position, most chemists aim to install a double bond between it and the α-carbon. David W. C. MacMillan and his team at Princeton University have now found a way to directly arylate the β-position of saturated aldehydes and ketones, opening up an easy path to more elaborate molecules (Science, DOI: 10.1126/science.1232993). The chemists use an iridium-based photoredox catalyst in combination with an organocatalyst containing an amine. The latter forms an enamine with the aldehyde or ketone, which then reacts with the photoredox catalyst to generate a radical. This species reacts with a cyano aryl group, which then eliminates cyanide. Hydrolysis of the amine catalyst finally generates a β-arylated aldehyde or ketone product. MacMillan’s group demonstrated the versatility of the reaction by using a broad range of aldehydes, ketones, and aryl groups (one shown).