Department of Chemistry, Columbia University, New York, New York 10027, United States.
J Am Chem Soc. 2020 Oct 28;142(43):18310-18316. doi: 10.1021/jacs.0c08595. Epub 2020 Oct 15.
Primary amines are often cheap, naturally occurring, and chemically diverse starting materials. For these reasons, deaminative functionalization of amines has emerged as an important area of research. Recent advances in C-N activation transform simple α-1° and α-2° amines into alkylating reagents via Katritzky pyridinium salts. We report a complementary method that activates sterically encumbered α-3° primary amines through visible light photoredox catalysis. By condensing α-3° primary amines with electron-rich aryl aldehyde, we enable an oxidation and deprotonation event, which generates a key imidoyl radical intermediate. A subsequent β-scission event liberates alkyl radicals for coupling with electron-deficient olefins for the generation of unnatural γ-quaternary amino acids and other valuable synthetic targets.
伯胺通常是廉价的、天然存在的、化学结构多样的起始原料。由于这些原因，胺的脱氨官能化已成为一个重要的研究领域。最近 C-N 活化的进展通过 Katritzky 吡啶鎓盐将简单的α-1°和α-2°胺转化为烷基化试剂。我们报告了一种互补的方法，通过可见光光氧化还原催化激活空间位阻较大的α-3°伯胺。通过缩合α-3°伯胺与富电子芳醛，我们可以实现氧化和去质子化反应，生成关键的酰基自由基中间体。随后的β-断裂事件释放出烷基自由基，与缺电子烯烃进行偶联，生成非天然的γ-季铵氨基酸和其他有价值的合成目标。
