Ma Panpan, Guo Ting, Lu Hongjian
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Normal University, Wuhu, Anhui, China.
Nat Commun. 2024 Nov 24;15(1):10190. doi: 10.1038/s41467-024-54599-y.
While selective defunctionalizations are valuable in organic synthesis, hydrodeamination of primary amines poses challenges. Deuterodeamination, analogous to hydrodeamination, presents even greater difficulties due to its frequently slower deuteration rate, interference by hydrogenation and constraints in deuterated sources. This study introduces a reliable, robust, and scalable hydro- and deuterodeamination method capable of handling various primary amines. Defined by its mild reaction conditions, rapid completion, simplified purification facilitated by water-soluble byproducts, the method leverages deuterium oxide as a deuterium source and employs commercialized O-diphenylphosphinylhydroxylamine for deamination. Applied to a diverse range of biologically active molecules, it has consistently achieved high yields and efficient deuterium incorporation. By synergizing with site-selective C-H functionalization of primary aliphatic amines, our method reveals synthetic strategies utilizing nitrogen atom as a traceless directing group, encompassing deaminative alkylation, 1,1-deuteroalkylation, 1,1-dialkylation, 1,1,1-deuterodialkylation, C-H arylation, and 1,3-deuteroarylation. Emphasizing this innovation, the processes of deaminative degree-controlled deuteration have been developed.
虽然选择性去功能化在有机合成中很有价值，但伯胺的加氢脱氨面临挑战。与加氢脱氨类似，氘代脱氨由于其氘代速率通常较慢、氢化干扰以及氘代源的限制而面临更大困难。本研究介绍了一种可靠、稳健且可扩展的加氢和氘代脱氨方法，该方法能够处理各种伯胺。该方法以温和的反应条件、快速完成反应、水溶性副产物便于简化纯化过程为特点，利用氧化氘作为氘源，并采用商业化的O-二苯基膦酰基羟胺进行脱氨反应。应用于各种生物活性分子时，该方法始终能实现高产率和高效的氘掺入。通过与伯脂肪胺的位点选择性C-H官能化协同作用，我们的方法揭示了利用氮原子作为无痕导向基团的合成策略，包括脱氨基烷基化、1,1-氘代烷基化、1,1-二烷基化、1,1,1-氘代二烷基化、C-H芳基化和1,3-氘代芳基化。强调这一创新，已开发出脱氨基程度可控的氘代过程。
