Sheng Tao, Zhuang Zhe, Zhao Zhihan, Hoque Md Emdadul, Yu Jin-Quan
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Angew Chem Int Ed Engl. 2025 Jan 21;64(4):e202416634. doi: 10.1002/anie.202416634. Epub 2024 Nov 16.
Despite extensive efforts to develop γ-lactamization reactions for pyrrolidinone synthesis using either cyclometallation, C-H insertion, or radical C-H abstraction strategies, γ-lactamization reactions of aliphatic amides using practical catalysts and common protecting groups remain extremely rare. Herein we report copper-catalyzed γ-C(sp)-H lactamization and iminolactonization of tosyl-protected aliphatic amides using inexpensive Selectfluor as the sole oxidant. A switchable selectivity of γ-lactams or γ-iminolactones can be obtained by using two different sets of reaction conditions. Notably, structurally diverse spiro-, fused-, and bridged-lactams and iminolactones, as well as isoindolinones are accessible by this method. Further derivatization of the γ-lactam products enables the synthesis of a range of biologically important motifs, including γ-amino acids, δ-amino alcohols, and pyrrolidines.
尽管人们付出了巨大努力，利用环金属化、C-H插入或自由基C-H攫取策略来开发用于吡咯烷酮合成的γ-内酰胺化反应，但使用实用催化剂和常见保护基团的脂肪族酰胺的γ-内酰胺化反应仍然极为罕见。在此，我们报道了使用廉价的Selectfluor作为唯一氧化剂，铜催化对甲苯磺酰基保护的脂肪族酰胺进行γ-C(sp)-H内酰胺化和亚胺内酯化反应。通过使用两组不同的反应条件，可以实现γ-内酰胺或γ-亚胺内酯的可切换选择性。值得注意的是，通过该方法可以获得结构多样的螺环、稠环和桥环内酰胺以及亚胺内酯，以及异吲哚啉酮。γ-内酰胺产物的进一步衍生化能够合成一系列具有生物学重要意义的结构单元，包括γ-氨基酸、δ-氨基醇和吡咯烷。
