2025-10-24 九州大学
図1. 本研究の合成スキーム：触媒的かつ穏和な条件でアミドとエステルの重水素化を達成。ルイス酸と塩基が付加体を形成せず、互いに独立かつ協奏的に機能することで従来は触媒的活性化が困難であったアミドおよびエステルを、穏和な条件下で活性化することに成功した。
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1309/
- https://www.kyushu-u.ac.jp/f/63727/25_1024_03.pdf
- https://www.nature.com/articles/s41929-025-01420-8
シリコンフラストレートルイス対はアミドおよびエステルのα重水素化を触媒する Silicon frustrated Lewis pairs catalyse α-deuteration of amides and esters
Y. Koga,I. Fukumoto,K. Masui,T. Tanaka,Y. Naganawa,M. Hayashi,T. Ohshima & R. Yazaki
Nature Catalysis Published:24 October 2025
DOI:https://doi.org/10.1038/s41929-025-01420-8
Abstract
Deuterium-labelled compounds play a crucial role in drug discovery as both diagnostic tools and deuterated pharmaceuticals. While hydrogen isotope exchange is well established for activated substrates, the catalytic deuteration of unactivated amides and esters remains underdeveloped, particularly under mild conditions suitable for sensitive pharmaceuticals and polymers. This limitation hampers the late-stage modification of pharmaceutical molecules and functional materials. Here we report a catalytic hydrogen isotope exchange method using cooperative catalysts—a silicon Lewis acid and a tertiary amine base—functioning as a frustrated Lewis pair. This approach enables highly selective deuteration under mild conditions. Our method achieves high deuterium incorporation in various functionalized pharmaceuticals and polyesters, including those typically unstable under basic conditions, demonstrating its broad applicability.
