Abstract：
The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging and attractive to explore. Herein, the first Brønsted-base catalyzed enantioselective (3+2) annulation of donor-acceptor cyclopropanes with aldehydes and ketones affording enantioenriched 2,3,5-substituted tetrahydrofurans is reported. The reaction concept is based on activation of racemic β-cyclopropyl ketones by a chiral bifunctional Brønsted base which catalyzes the (3+2) annulation for a range of aldehydes and ketones. For aldehydes, the annulation furnished tetrahydrofurans in excellent yield, good diastereoselectivity and with excellent enantioselectivity up to >99% ee. Surprisingly, aromatic aldehydes afforded the cis-2,5-substituted tetrahydrofurans as the major diastereoisomer, while for aliphatic aldehydes the trans-cycloadduct was favored. The reaction also proceeds well for ketones affording spiro tetrahydrofurans in excellent yields and enantioselectivities (up to 99% ee). Hammett studies have been conducted to elucidate the influence of the electronic nature of benzaldehydes on the stereoselectivity. Based on the diastereochemical outcome for the aldehydes, two reaction paths for aromatic and aliphatic aldehydes are proposed. Finally, two diastereoselective synthetic transformations have been conducted to demonstrate the synthetic potential of the obtained products.
摘要：
取代的四氢呋喃核心是许多生物活性和天然化合物中的结构基序。然而,对映体选择性方法的缺乏对其合成的发展使得该领域具有挑战性和有吸引力的探索。在这里，据报道，供体-受体环丙烷与醛和酮的第一个布朗斯台德碱催化的对映选择性（32）环化，得到对映富集的2,3,5-取代的四氢呋喃。该反应概念基于手性双官能布朗斯台德碱对外消旋β-环丙基酮的活化，该碱催化一系列醛和酮的（32）环化。对于醛，环化以优异的收率提供四氢呋喃，良好的非对映选择性和优异的对映选择性>99%ee。令人惊讶的是,芳香醛提供顺式-2,5-取代的四氢呋喃作为主要的非对映异构体，而对于脂肪醛，反式-环加合物是有利的。对于酮,反应也进行得很好,以优异的产率和对映选择性(高达99%ee)得到螺四氢呋喃。已经进行了Hammett研究以阐明苯甲醛的电子性质对立体选择性的影响。根据醛的非对映化学结果，提出了芳香族醛和脂肪醛的两种反应路径。最后,已经进行了两次非对映选择性合成转化以证明所得产物的合成潜力。
