Department of Chemistry, The University of Utah, Salt Lake City, UT, USA.
Department of Chemistry, University of California, Berkeley, CA, USA.
Nat Chem. 2019 Aug;11(8):710-715. doi: 10.1038/s41557-019-0289-7. Epub 2019 Jul 15.
The carbon-fluorine bond engenders distinctive physicochemical properties and significant changes to general reactivity. The development of catalytic, enantioselective methods to set stereocentres that contain a benzylic C-F bond is a rapidly evolving goal in synthetic chemistry. Although there have been notable advances that enable the construction of secondary stereocentres that contain both a C-F and a C-H bond on the same carbon, significantly fewer strategies are defined to access stereocentres that incorporate a tertiary C-F bond, especially those remote from pre-existing activating groups. Here we report a general method that establishes C-F tertiary benzylic stereocentres by forging a C-C bond via a Pd-catalysed enantioselective Heck reaction of acyclic alkenyl fluorides with arylboronic acids. This method provides a platform to rapidly incorporate significant functionality about the benzylic tertiary fluoride by virtue of the diversity of both reaction partners, as well as the ability to install the stereocentres remotely from pre-existing functional groups.
碳氟键赋予了独特的物理化学性质和显著的反应性变化。开发催化、对映选择性的方法来构建含有苄基 C-F 键的立体中心是合成化学中一个快速发展的目标。尽管已经有了显著的进展，可以构建同时含有 C-F 和 C-H 键的次级立体中心，但定义的方法很少能够获得包含三级 C-F 键的立体中心，特别是那些远离现有活化基团的立体中心。在这里，我们报告了一种通过钯催化的非环烯基氟化物与芳基硼酸的对映选择性 Heck 反应形成 C-C 键来建立 C-F 三级苄基立体中心的通用方法。该方法通过反应伙伴的多样性以及从现有官能团远程安装立体中心的能力，为在苄基三级氟化物上快速引入重要官能团提供了一个平台。
