Mechanical‐Force‐Induced Non‐spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst

• Published in: Angewandte Chemie Vol. 136; no. 28
• Main Authors: Qu, Ruiling, Wan, Shan, Zhang, Xuemei, Wang, Xiaohong, Xue, Li, Wang, Qingqing, Cheng, Gui‐Juan, Dai, Lunzhi, Lian, Zhong
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 08.07.2024
• Subjects: Analytical chemistry; Ball milling; Biological activity; Catalysts; Chemical synthesis; dehalogenative deuteration; deuterated drugs; Deuteration; Deuterium; Iodides; Ipriflavone; Labeling; Mechanical properties; mechanochemistry; non-spontaneous reaction; Osteoclastogenesis; Piezoelectricity; Reducing agents
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202400645

The development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid‐phase system under ball‐milling conditions. This non‐spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D‐ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro. We have developed a catalytic, non‐spontaneous dehalogenation process for the deuteration of aryl iodides using BaTiO3 as a catalyst. This method achieves high levels of deuterium incorporation using only 2.0 equivalents of D2O, which additionally acts as an electron donor. Furthermore, deuteration enhances the biological activity of D‐ipriflavone, markedly inhibiting osteoclast differentiation.