Divalent samarium (Sm) compounds play a vital role as reagents in reductive transformations within organic chemistry. However, the typical processes require substantial quantities of this reagent and often involve the use of toxic chemicals. To tackle this challenge, researchers have crafted a visible-light-antenna ligand that bonds with stable trivalent samarium compounds. When exposed to visible light, these compounds are converted into divalent samarium, which allows for milder reaction conditions and less samarium usage.
Samarium (Sm), a rare earth element, holds significance for organic chemists due to its divalent compounds’ effectiveness in executing single-electron transfer reductions. Samarium iodide (SmI2) boasts moderate stability and can function under gentle conditions at room temperature, making it a valuable resource in the production of pharmaceuticals and biologically active substances. However, many reactions necessitate SmI2 in quantities at least equal to the stoichiometric requirement, along with the use of hazardous chemicals, rendering these procedures resource-intensive and costly.
Various strategies have been explored to minimize the required amounts of Sm reagents to catalytic levels. Unfortunately, most existing methods demand harsh conditions and highly reactive reducing agents while still requiring significant Sm amounts, often ranging from 10-20% of the raw materials. Given the high cost of Sm, an efficient catalytic system that employs minimal Sm under gentler conditions is in high demand.
In a recent advancement, a research team from Chiba University in Japan, led by Assistant Professor Takahito Kuribara from the Institute for Advanced Academic Research and the Graduate School of Pharmaceutical Sciences, has introduced a novel approach that significantly cuts down on Sm usage. They developed a bidentate phosphine oxide ligand, substituted with 9,10-diphenyl anthracene (DPA), which coordinates with trivalent samarium, allowing the exploitation of visible light for Sm-catalyzed reductive transformations. This ligand is referred to as a visible-light antenna. Assistant Professor Kuribara shares, “Antenna ligands are recognized for their ability to energize lanthanoid metals like Sm. Previously, we demonstrated a DPA-substituted secondary phosphine oxide ligand capable of facilitating reduction-oxidation reactions under visible light. Based on this success, we designed a new DPA-substituted bidentate phosphine oxide ligand that harnesses visible light to reduce the required Sm to a catalytic amount.”
The research team included Ayahito Kaneki, Yu Matsuda, and Tetsuhiro Nemoto from the Graduate School of Pharmaceutical Sciences at Chiba University. Their findings were published online on July 20, 2024, and appeared in Volume 146, Issue 30 of the Journal of the American Chemical Society on July 31, 2024.
Through various experiments, the research team demonstrated that using the Sm catalyst in combination with DPA-1 under blue-light exposure resulted in high yields—up to 98%—in pinacol coupling reactions involving aldehydes and ketones, which are frequently utilized in pharmaceuticals. Impressively, these reactions could occur with only 1-2 mol% of the Sm catalyst, marking a considerable reduction compared to the typical stoichiometric amounts needed. Additionally, reactions could proceed using mild organic reducing agents like amines, contrasting with the highly reactive agents previously required.
Results indicated that a small addition of water enhanced yields, while excessive water hampered the reaction. In comparison, ligands DPA-2 and DPA, despite having similar structures to DPA-1, resulted in poor performance.
To grasp why DPA-1 was so effective, the researchers investigated the emission properties of the Sm catalyst when combined with DPA-1. They discovered that DPA-1 acts as a multifunctional ligand that binds with Sm, selectively absorbs blue light, and efficiently transfers electrons from the antenna to Sm.
The researchers successfully employed the Sm catalyst alongside DPA-1 in a range of molecular transformation reactions, including carbon-carbon bond formations and cleavings, which are essential for drug development. Furthermore, using visible light as an energy source allowed for molecular transformations that integrated Sm-based reductions with photo-oxidation.
“Our new visible-light antenna ligand has reduced the amount of Sm needed to just 1-2 mol%, a significant decrease from the previous stoichiometric requirements, by utilizing low-energy visible light,” states Assistant Professor Kuribara. He further adds, “Importantly, we were able to start with trivalent Sm, which is more stable and easier to manage compared to divalent Sm.”
This study provides crucial insights for the continued development and design of Sm-based catalysts, representing a major advancement in organic chemistry by enabling efficient Sm-catalyzed reductive transformations under mild conditions with diminished Sm requirements.
