Copper(I)-catalyzed diastereo- and enantio-selective construction of optically pure exocyclic allenes
Copper(I)-catalyzed diastereo- and enantio-selective construction of optically pure exocyclic allenes
复制标题
铜(I)催化的光学纯环外联烯的非对映和对映选择性构建
DOI：
10.1038/s41467-020-18136-x
复制
发表时间：
2020-08-27
影响因子：
16.6
通讯作者：
Lin, Guo-Qiang
中科院分区：
文献类型：
--
作者：
He, Cheng-Yu;Tan, Yun-Xuan;Lin, Guo-Qiang
在约150种已鉴定的丙二烯类天然产物中，环外丙二烯是一个主要的亚类。人们在轴向手性联烯的构建方面付出了巨大的努力，但制备手性环外联烯的策略仍然很少。在此，我们提出了一种有效的策略，通过铜（I）催化的不对称分子内还原偶联的1，3-烯炔环己二烯酮的手性环外联烯的不对称合成的同时控制轴向和中心手性。该串联反应具有良好的官能团相容性，得到了相应的光学纯的环外联烯化合物，这些化合物具有顺式氢苯并呋喃、顺式氢吲哚和顺式氢茚骨架，产率高达99%，非对映选择性一般大于20：1dr，对映选择性大多大于99%ee.此外，还介绍了一个克级实验和几种手性环外联烯的合成转化。尽管人们在轴向手性联烯的构建方面做了大量的工作，但手性环外联烯的制备策略还不多见。本工作描述了一种同时控制轴手性和中心手性的铜催化环外联烯的不对称合成方法。
Among about 150 identified allenic natural products, the exocyclic allenes constitute a major subclass. Substantial efforts are devoted to the construction of axially chiral allenes, however, the strategies to prepare chiral exocyclic allenes are still rare. Herein, we show an efficient strategy for the asymmetric synthesis of chiral exocyclic allenes with the simultaneous control of axial and central chirality through copper(I)-catalyzed asymmetric intramolecular reductive coupling of 1,3-enynes to cyclohexadienones. This tandem reaction exhibits good functional group compatibility and the corresponding optically pure exocyclic allenes bearing cis-hydrobenzofuran, cis-hydroindole, and cis-hydroindene frameworks, are obtained with high yields (up to 99% yield), excellent diastereoselectivities (generally >20:1dr) and enantioselectivities (mostly >99%ee). Furthermore, a gram-scale experiment and several synthetic transformations of the chiral exocyclic allenes are also presented. Substantial efforts have been devoted to the construction of axially chiral allenes, however, the strategies to prepare chiral exocyclic allenes are still rare. This work describes a copper-catalyzed asymmetric synthesis of exocyclic allenes by simultaneous control of axial and central chirality.