Enantioselective Synthesis of Cyclobutane Derivatives via Cascade Asymmetric Allylic Etherification/[2 + 2] Photocycloaddition

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.手性环丁烷（chiral cyclobutane）是天然产物与生物活性分子中常见的结构基序，其衍生物已被广泛用作有机合成中的关键合成子。本文报道了一种制备对映富集型环丁烷衍生物的高效合成方法。该反应以级联路径进行，涉及铱（Ir）催化的不对称烯丙基醚化反应与可见光诱导的[2+2]环加成反应。该方法以易得的支链烯丙基乙酸酯与肉桂醇为底物，在温和反应条件下直接开展反应，可得到一系列结构多样的手性环丁烷产物，且产物兼具良好收率与优异的非对映选择性和对映选择性（最高可达12:1的非对映选择性比（dr），对映体过量值（ee）>99%）。值得注意的是，该策略无需分步操作，可将所有底物与催化剂同时加入反应体系。克级规模反应的实现以及产物的多样衍生化进一步提升了该方法的应用价值。