Access to relatively high energy azetidines in enantioenriched form via a function- and diversity-oriented approach is highly desired in the field of drug-discovery. Although the demands for α-trifluoromethyl azetidines with great biological potential exist, effective strategies for catalytic asymmetric synthesis of these chemical entities with structural diversity remain elusive. To conquer this frontier, we, herein, report the development of a building block protocol for the facile assembly of enantioenriched α-trifluoromethyl azetidines via peptide-mimic phosphonium salt-catalyzed asymmetric [2 + 2] cycloadditions of tethered trifluoromethyl ketimines and allenes. Of note, this methodology could allow for the enantioselective synthesis of a diverse set of six-membered ring-fused α-trifluoromethyl azetidines bearing two densely functionalized carbon stereocenters in high yields with excellent diastereo- and enantioselectivities. Besides the fundamental appeal of this strategy, scale-up experiment and representative transformations could engender its prompt application in synthetic chemistry.

中文翻译：

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有机催化对映选择性 [2 + 2] 针对手性熔融 -三氟甲基氮杂替胺的环加成反应


在药物发现领域，非常需要通过面向功能和多样性的方法以对映体富集形式获得相对高能量的氮杂替丁。尽管存在对具有巨大生物学潜力的 α-三氟甲基氮杂环胺的需求，但催化不对称合成这些具有结构多样性的化学实体的有效策略仍然难以捉摸。为了征服这一前沿领域，我们在此报告了一种构建块方案的开发，用于通过肽模拟鏻盐催化的不对称 [2 + 2] 束缚三氟甲基酮胺和等位化合物的对映体富集 α-三氟甲基氮杂替胺的简单组装。值得注意的是，这种方法可以允许对映选择性合成一组多样化的六元环熔 α-三氟甲基氮杂代丁，这些氮杂乙胺带有两个致密官能化的碳立体中心，产率高，具有出色的非对映和对映选择性。除了该策略的基本吸引力外，放大实验和代表性转化还可以使其在合成化学中迅速应用。