Synthesis of Vinyl Azetidines and β‑Lactams from Allenamides via Energy-Transfer Relay

Azetidines and β-lactams are useful and versatile building blocks with ample synthetic applications and pharmaceutical uses. However, few catalytic methods provide densely functionalized monocyclic derivatives, and none could easily afford both azetidines and β-lactams. Herein, we solved this issue with allenamides. The challenging substrates were activated by energy transfer combining a tailor-made Ir(III) complex and a binaphthyl cocatalyst, which acts as a triplet-state relay and stabilizes intermediates via dispersion interactions. A triplet intermediate with a vinyl-radical character gives the strained heterocycles upon 1,5 hydrogen atom transfer. Products have a congested all-carbon quaternary center and a useful allylamine unit and are prepared at room temperature with complete atom economy. The utility of the method is shown by further downstream derivatization.氮杂环丁烷(azetidines)与β-内酰胺类(β-lactams)是一类多功能且极具应用价值的合成砌块，具备丰富的合成应用潜力与药用用途。然而目前鲜有催化合成策略能够制备高官能团化的单环衍生物，且尚无方法可同时便捷地合成这两类化合物。本研究以联烯酰胺(allenamides)为底物，解决了上述难题。反应中，具有挑战性的底物通过能量转移策略实现活化：体系采用定制化铱(III)配合物(Ir(III) complex)与联萘助催化剂(binaphthyl cocatalyst)，其中联萘助催化剂可充当三重态中继器(triplet-state relay)，并通过色散相互作用稳定反应中间体。带有乙烯基自由基特征的三重态中间体经1,5-氢原子转移(1,5 hydrogen atom transfer)后，即可生成具有环张力的杂环产物。所得产物兼具拥挤的全碳季碳中心与实用的烯丙胺结构单元，且可在室温条件下以完全原子经济性实现合成。该方法的合成实用性可通过进一步的下游衍生化反应得到验证。