Tsuji Taro, Fukumoto Isora, Hario Takara, Hayashi Mikihiro, Osawa Ayumi, Ohshima Takashi, Yazaki Ryo
Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan.
Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho Showa-ku Nagoya-city, Aichi, Japan.
Nat Commun. 2025 Jul 7;16(1):6266. doi: 10.1038/s41467-025-61662-9.
Primary amines are highly ubiquitous functional groups found in diverse natural products and building blocks. Despite their widespread application as nucleophiles, the potential for facile deaminative functionalization utilizing primary amines, particularly sterically hindered α-tertiary amines, has remained less explored. Herein, we report catalytic direct synthesis of aliphatic diazenes from sterically hindered α-tertiary amines. The catalytic diazene synthetic method exhibits wide functional group tolerance, allowing for expeditious access to a wide array of hitherto-inaccessible, highly congested diazenes in a short time. Noteworthy is that the present catalytic method enables the synthesis of various hetero-diazenes using distinct α-tertiary amines in just one step for the first time. The catalytic process could also be readily incorporated into Fmoc solid-phase peptide synthesis, enabling the synthesis of elastin-derived diazene, which contains 12 amino acid residues. The catalytic diazene synthetic method enables efficient deaminative transformation of C-N bonds into C-halogen, C-H, C-O, C-S, C-Se, and C-C bonds through carbon-centered radical formation.
伯胺是存在于多种天然产物和结构单元中的高度普遍存在的官能团。尽管它们作为亲核试剂有广泛应用，但利用伯胺，特别是空间位阻较大的α-叔胺进行简便的脱氨基官能化的潜力仍未得到充分探索。在此，我们报道了从空间位阻较大的α-叔胺催化直接合成脂肪族重氮化合物。这种催化重氮化合物合成方法具有广泛的官能团耐受性，能够在短时间内快速获得一系列迄今无法获得的、高度拥挤的重氮化合物。值得注意的是，本催化方法首次能够仅通过一步反应，使用不同的α-叔胺合成各种杂重氮化合物。该催化过程还可以很容易地纳入Fmoc固相肽合成中，从而能够合成含有12个氨基酸残基的弹性蛋白衍生重氮化合物。这种催化重氮化合物合成方法能够通过形成碳中心自由基，将C-N键高效地脱氨基转化为C-卤素、C-H、C-O、C-S、C-Se和C-C键。
