Aida Kazuhiro, Hirao Marina, Saitoh Tsuyoshi, Yamamoto Takashi, Einaga Yasuaki, Ota Eisuke, Yamaguchi Junichiro
Department of Applied Chemistry, Waseda University, 513 Wasedatsurumakicho, Shinjuku, Tokyo 162-0041, Japan.
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
J Am Chem Soc. 2024 Nov 6;146(44):30698-30707. doi: 10.1021/jacs.4c13210. Epub 2024 Oct 23.
Cleavage of inert C-N bonds in unstrained azacycles such as pyrrolidine remains a formidable challenge in synthetic chemistry. To address this, we introduce an effective strategy for the reductive cleavage of the C-N bond in -benzoyl pyrrolidine, leveraging a combination of Lewis acid and photoredox catalysis. This method involves single-electron transfer to the amide, followed by site-selective cleavage at the C2-N bond. Cyclic voltammetry and NMR studies demonstrated that the Lewis acid is crucial for promoting the single-electron transfer from the photoredox catalyst to the amide carbonyl group. This protocol is widely applicable to various pyrrolidine-containing molecules and enables inert C-N bond cleavage including C-C bond formation via intermolecular radical addition. Furthermore, the current protocol successfully converts pyrrolidines to aziridines, γ-lactones, and tetrahydrofurans, showcasing its potential of the inert C-N bond cleavage for expanding synthetic strategies.
在合成化学中，诸如吡咯烷等无张力氮杂环中惰性碳-氮键的裂解仍然是一项艰巨的挑战。为了解决这一问题，我们引入了一种有效的策略，利用路易斯酸和光氧化还原催化相结合的方法，实现对N-苯甲酰基吡咯烷中碳-氮键的还原裂解。该方法涉及单电子转移至酰胺，随后在C2-N键处进行位点选择性裂解。循环伏安法和核磁共振研究表明，路易斯酸对于促进光氧化还原催化剂向酰胺羰基的单电子转移至关重要。该方案广泛适用于各种含吡咯烷的分子，并能够实现惰性碳-氮键的裂解，包括通过分子间自由基加成形成碳-碳键。此外，当前方案成功地将吡咯烷转化为氮丙啶、γ-内酯和四氢呋喃，展示了其在扩展合成策略方面惰性碳-氮键裂解的潜力。
