Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds

• Published in: Nature communications Vol. 13; no. 1; pp. 4224 - 8
• Main Authors: Li, Nian, Li, Jinhang, Qin, Mingzhe, Li, Jiajun, Han, Jie, Zhu, Chengjian, Li, Weipeng, Xie, Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.07.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/439/890; Amides; Catalysis; Chemical bonds; Chemistry; Deuteration; Deuterium; Exchanging; Humanities and Social Sciences; Hydrogen; Hydrogen atoms; Hydrogen bonds; Hydrogen-deuterium exchange; multidisciplinary; Pharmaceuticals; Photocatalysis; Radicals; Science; Science (multidisciplinary); Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31956-3

Selective deuteration of unactivated C(sp 3 )-H bonds is a highly attractive but challenging subject of research in pharmaceutical chemistry, material science and synthetic chemistry. Reported herein is a practical, highly selective and economical efficient hydrogen/deuterium (H/D) exchange of unactivated C(sp 3 )-H bonds by synergistic photocatalysis and hydrogen atom transfer (HAT) catalysis. With the easily prepared PMP-substituted amides as nitrogen-centered radical precursors, a wide range of structurally diverse amides can undergo predictable radical H/D exchange smoothly with inexpensive D 2 O as the sole deuterium source, giving rise to the distal tertiary, secondary and primary C(sp 3 )-H bonds selectively deuterated products in yields of up to 99% and excellent D-incorporations. In addition to precise monodeuteration, this strategy can also achieve multideuteration of the substrates contain more than one remote C(sp 3 )-H bond, which opens a method to address multi-functionalization of distal unactivated C(sp 3 )–H bonds. Deuteration of unactivated C(sp3)̵̵̵̵̵̵̵̵–H bonds is a simple route to deuterated compounds, of use in pharmaceutical chemistry, material science, and synthetic chemistry. Here, the authors describe a hydrogen/deuterium (H/D) exchange of remote unactivated C(sp3)̵̵̵̵̵̵̵̵–H bonds via photocatalysis, proceeding through hydrogen atom transfer.