I have been intrigued by a series of papers from the lab of Professor Xiao of SIOC. The latest one just appeared in JOC and followed the Nat. Comm. report, which came out earlier this year. The reaction described in the JOC paper offers a route to difluoroethylated alcohols and amines. While it is easy to see why difluoroethylated molecules might be of interest in drug discovery programs, I am particularly intrigued by the mechanistic underpinnings of the Xiao process. Positively charged phosphonium cation is the source of the nucleophilic difluoroethyl group. The reaction appears to involve carbonate addition to phosphorous, at which points the “baton” is passed to the thermodynamics of the phosphorus-oxygen bond. This strong link is the reason why a nucleophile emerges from what is originally an electrophilic phosphorus component. By the way, this gives me an opportunity to lament, once again, on the ultimate origin of some common chemicals we take for granted. Take the venerable triphenylphosphine. Out of curiosity, I peeked into the Encyclopedia of Industrial Chemicals only to find out that this molecule is still produced from chlorobenene, sodium, and phosphorus tricholoride under intensive cooling. The corresponding oxide, which is made in almost all applications of triphenylphosphine in organic chemistry, is recycled by the likes of BASF using phosgene to first generate the Ph3PCl2 derivative, which is then reduced with aluminum. Wow. Talk about tracing common chemicals to their metallic origins (see my previous post).