Phosphenium Catalysis

Dihydropyridines (DHP) are a class of chemicals with important pharmaceutical applications, including drugs for treating hypertension, as well as serving important functions in basic biological processes. The research group of Rei Kinjo at Nanyang Technological University, Singapore, has recently discovered a groundbreaking procedure for synthesizing DHP that is cheap, efficient, and non-toxic. Their work was published in the Journal of the American Chemical Society in January 2018.

DHP is structurally very similar to pyridines, organic compounds that are cheap and easy to synthesize. However, previous methods for converting pyridines to DHP have all been uneconomical, due to requiring dangerous and expensive chemicals, with the result that DHP compounds have been manufactured from completely different starting materials instead. In recent years, researchers have developed catalysts for converting pydridines to DHP, but these catalysts contained toxic heavy metals such as rhodium or ruthenium, which cannot be used in manufacturing pharmaceuticals.

Professor Kinjo and his group have now developed a metal-free catalyst for converting pyridines into various DHP compounds. The new catalyst, called 1,3,2-Diazaphosphenium Triflate (NHP-OTf), functions at room temperature and is chemically straightforward to use. This discovery is significant because it opens up an economical and environmentally-friendly route for synthesizing numerous important drugs.

The new catalyst, NHP-OTf, is noteworthy not only for its potential applications, but also for its scientific novelty. “In the whole history of phosphorus chemistry, nobody has utilized this particular chemical group — dicoordinated phosphorus cations — for catalysis before,” says Professor Kinjo. “This is really the first example, and it might be the start of a whole new field of phosphenium catalysis.”

Reference:

B. Rao, C. C. Chong, and R. Kinjo, Metal-Free Regio- and Chemoselective Hydroboration of Pyridines Catalyzed by 1,3,2-Diazaphosphenium Triflate, Journal of the American Chemical Society 140, 652 (2018).