Catalytic Enantioselective Synthesis of Cyclobutenes from Alkynes and Alkenyl Derivatives
Catalytic Enantioselective Synthesis of Cyclobutenes from Alkynes and Alkenyl Derivatives
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DOI：
10.1021/jacs.9b07885
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发表时间：
2019-09-25
影响因子：
15
通讯作者：
RajanBabu, T., V
中科院分区：
文献类型：
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作者：
Parsutkar, Mahesh M.;Pagar, Vinayak Vishnu;RajanBabu, T., V
手性化合物的设计、合成以及最终规模化生产将对手性化合物的设计、合成和最终规模化生产产生重大影响。功能化的环丁烷和环丁烯是许多生物活性天然产物和与药物相关的小分子中的重要结构基元。它们也是其他类型的有机化合物的有用的前体，如其他环烷烃衍生物、杂环化合物、立体定义的1，3-二烯和用于催化不对称合成的配体。合成环丁烯的最简单的方法是通过炔烃和烯基衍生物之间的不对称[2+2]-环加成反应，这个反应有很长的历史。然而，已知的这类给出可接受的对映选择性的反应范围非常窄，并且严格限制在活化炔和高活性烯烃中。在这里，我们公开了一种广泛适用的对映体选择性[2+2]-烯烃和烯基衍生物之间的环加成反应，这是两类最丰富的有机前体。关键的环加成反应使用的催化剂来自于容易合成的配体和富含稀土的金属钴。记录了50多种不同的环丁烯，对映体选择性在86-97%ee的范围内。由于这些化合物中存在不同的官能团，因此很容易设想进一步的非对映选择性转化来合成高度官能化的环丁烷和环丁烯。在这些研究中所做的一些新的观察，包括阳离子Co(I)的关键作用-中间体、配体和反离子对反应的影响，可以预期在均相催化中具有广泛的意义，而不仅仅是通过这一路线可以获得的高价值的合成中间体。
Discovery of enantioselective catalytic reactions for the preparation of chiral compounds from readily available precursors, using scalable and environmentally benign chemistry, can greatly impact their design, synthesis, and eventually manufacture on scale. Functionalized cyclobutanes and cyclobutenes are important structural motifs seen in many bioactive natural products and pharmaceutically relevant small molecules. They are also useful precursors for other classes of organic compounds such as other cycloalkane derivatives, heterocyclic compounds, stereodefined 1,3-dienes, and ligands for catalytic asymmetric synthesis. The simplest approach to make cyclobutenes is through an enantioselective [2 + 2]-cycloaddition between an alkyne and an alkenyl derivative, a reaction which has a long history. Yet known reactions of this class that give acceptable enantioselectivities are of very narrow scope and are strictly limited to activated alkynes and highly reactive alkenes. Here, we disclose a broadly applicable enantioselective [2 + 2]-cycloaddition between wide variety of alkynes and alkenyl derivatives, two of the most abundant classes of organic precursors. The key cycloaddition reaction employs catalysts derived from readily synthesized ligands and an earth-abundant metal, cobalt. Over 50 different cyclobutenes with enantioselectivities in the range of 86-97% ee are documented. With the diverse functional groups present in these compounds, further diastereoselective transformations are easily envisaged for synthesis of highly functionalized cyclobutanes and cyclobutenes. Some of the novel observations made during these studies including a key role of a cationic Co(I)-intermediate, ligand and counterion effects on the reactions, can be expected to have broad implications in homogeneous catalysis beyond the highly valuable synthetic intermediates that are accessible by this route.