Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, China.
Key Laboratory of Computational Catalytic Chemistry of Guizhou Province, Department of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun, 558000, China.
Nat Commun. 2022 May 2;13(1):2393. doi: 10.1038/s41467-022-29985-z.
Derivatization of azaarenes can create molecules of biological importance, but reductive functionalization of weakly reactive azaarenes remains a challenge. Here the authors show a dearomative, diastereoselective annulation of azaarenes, via ruthenium(II) reductive catalysis, proceeding with excellent selectivity, mild conditions, and broad substrate and functional group compatibility. Mechanistic studies reveal that the products are formed via hydride transfer-initiated β-aminomethylation and α-arylation of the pyridyl core in the azaarenes, and that paraformaldehyde serves as both the C1-building block and reductant precursor, and the use of Mg(OMe) base plays a critical role in determining the reaction chemo-selectivity by lowering the hydrogen transfer rate. The present work opens a door to further develop valuable reductive functionalization of unsaturated systems by taking profit of formaldehyde-endowed two functions.
氮杂芳烃的衍生化可以创造出具有生物重要性的分子，但弱反应性氮杂芳烃的还原官能化仍然是一个挑战。在这里，作者通过钌（II）还原催化展示了氮杂芳烃的 dearomative、非对映选择性环化，具有极好的选择性、温和的条件以及广泛的底物和官能团兼容性。机理研究表明，产物是通过氮杂芳烃中吡啶核的氢化物转移引发的β-氨甲基化和α-芳基化形成的，多聚甲醛既是 C1 构建块又是还原剂前体，使用 Mg(OMe) 碱通过降低氢转移速率在确定反应化学选择性方面起着关键作用。本工作为进一步开发利用甲醛赋予的两种功能对不饱和体系进行有价值的还原官能化开辟了道路。
