A team of organic chemists at the University of California Los Angeles (UCLA) has developed a new way to use phosphorus as a catalyst in chemical reactions, a role typically reserved for rare and expensive metals such as platinum and palladium. Their findings, published in Nature, could lead to lower production costs in the pharmaceutical industry.
The researchers discovered that by using a light-reactive molecule, or photocatalyst, they could activate an inexpensive phosphorus compound to join nitrogen-containing compounds with carbon-carbon double bonds. This process, called hydroamination, is commonly used to create more complex molecular structures needed for drug development.
“Carbon-nitrogen bonds are some of the most important kinds of bonds for drug discovery and manufacturing. Almost all medicines have nitrogen in them, but fixing that nitrogen into molecules is difficult, which is why we use precious transition metal catalysts,” said Abigail Doyle, UCLA chemistry professor and corresponding author on the study.
Transition metals like gold, silver, copper, iridium, platinum and palladium are valued for their ability to speed up chemical reactions. These metals are widely used not only in industrial applications such as catalytic converters in car engines but also in producing materials ranging from textiles to pharmaceuticals. However, due to their cost and scarcity, there is ongoing interest in finding alternatives—either less expensive transition metals or elements from other groups on the periodic table that can perform similar functions.
“These metals are used in catalytic converters in car engines, and to make a vast variety of materials, from components of denim jeans to medicines,” Doyle explained. “However, they can be very expensive to use, so there’s a lot of interest in either finding less expensive transition metals to replace these, such as copper, nickel or iron, or to find a catalyst from a different block in the periodic table that is both abundant and can also react the way that metals do.”
Phosphorus is already known as an essential element for life and has widespread use in organic chemistry. Phosphines—molecules containing one phosphorus atom bonded with three carbon atoms—have previously served as catalysts.
“But we’ve discovered a new reactivity mode for phosphorus that mimics a mode that transition metals like palladium and iridium commonly perform in catalysis,” Doyle added.
First author Flora Fan noted the unexpected nature of their results: “We were surprised to see high reactivity for a completely different product than what we expected. It was definitely a puzzle to try to figure out what was going on.” Further investigation revealed that phosphorus was behaving similarly to metal catalysts during these reactions.
The process works through an unstable form of phosphorus capable of reacting with carbon-carbon double bonds much like traditional metal catalysts do—but via different mechanisms. Unlike typical transition metal catalysts that involve transferring two electrons at once during reactions, phosphine can transfer either one or two electrons depending on its state. This opens possibilities for new types of hydroamination reactions using diverse nitrogen-containing compounds.
Doyle’s group hopes this work will inspire more research into phosphorus-based catalysts for designing future chemical processes. “We’re excited about trying to understand how far we can take this chemistry,” said Fan. “Hopefully it will open doors to more versatile methods for making drug compounds and other value-added chemicals.”
Other authors on the paper include UCLA doctoral student Alexander Maertens and Princeton Ph.D. Kassandra Sedillo. The project received funding support from the National Institutes of Health.
UCLA has gained recognition nationally and internationally through achievements by Nobel laureates and MacArthur Fellows according to its official website. The university also maintains excellence across scholarship fields including arts and athletics while supporting research activities on its 419-acre campus within the University of California system (source). UCLA encourages diversity through academic programs designed around inclusive environments (source).
