Stereodivergent Construction of Tertiary Fluorides in Vicinal Stereogenic Pairs by Allylic Substitution with Iridium and Copper Catalysts
Stereodivergent Construction of Tertiary Fluorides in Vicinal Stereogenic Pairs by Allylic Substitution with Iridium and Copper Catalysts
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DOI：
10.1021/jacs.9b04440
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发表时间：
2019-08-21
影响因子：
15
通讯作者：
Hartwig, John F.
中科院分区：
文献类型：
--
作者：
He, Zhi-Tao;Jiang, Xingyu;Hartwig, John F.
尽管已经在叔烷基氟化物的对映选择性合成上花费了很多努力，但是在立体中心阵列（特别是两个邻位立体中心）内含有这种立体中心的化合物的合成仍然是合成挑战，并且没有报道独立地控制每个立体中心的构型的方法。我们描述了一种策略，以实现这样的立体分散合成的邻位立体中心，一个含有氟原子，通过形成连接的碳-碳键与催化剂系统，包括铱络合物，控制在亲电碳的配置和铜催化剂，控制在亲核含氟碳的配置。这些反应与烷基和芳基取代的烯丙基酯和氮杂芳基酮、酯和酰胺的不稳定烯醇化物以高产率、非对映选择性和对映选择性（通常>90%产率，>20：1 dr，97- 99%ee）发生。获得产品的所有四种立体异构体证明了对两种构型的独立精确控制。该方法以类似的高产率和选择性延伸到邻位四级和三级立体中心的立体分散构建。DFT计算揭示了烯丙基取代反应中烯醇化铜立体选择性的起源。
Although much effort has been spent on the enantioselective synthesis of tertiary alkyl fluorides, the synthesis of compounds containing such a stereogenic center within an array of stereocenters, particularly two vicinal ones, remains a synthetic challenge, and no method to control the configuration of each stereogenic center independently has been reported. We describe a strategy to achieve such a stereodivergent synthesis of vicinal stereogenic centers, one containing a fluorine atom, by forming the connecting carbon-carbon bond with a catalyst system comprising an iridium complex that controls the configuration at the electrophilic carbon and a copper catalyst that controls the configuration at the nucleophilic fluorine-containing carbon. These reactions occur with alkyl-and aryl-substituted allylic esters and the unstabilized enolates of azaaryl ketones, esters, and amides in high yield, diastereoselectivity, and enantioselectivity (generally >90% yield, >20:1 dr, 97-99% ee). Access to all four stereoisomers of products demonstrates the precise control of the two configurations independently. This methodology extends to the stereodivergent construction of vicinal quaternary and tertiary stereocenters in similarly high yield and selectivity. DFT calculations uncover the origin of stereoselectivity of copper enolate in allylic substitution.