Department of Chemistry, Yale University, 225 Prospect St., New Haven, CT, 06520, USA.
Angew Chem Int Ed Engl. 2017 Jul 24;56(31):9183-9187. doi: 10.1002/anie.201703967. Epub 2017 Jul 5.
The first syntheses of privileged [5,6]-bicyclic heterocycles, with ring-junction nitrogen atoms, by transition metal catalyzed C-H functionalization of C-alkenyl azoles is disclosed. Several reactions are applied to alkenyl imidazoles, pyrazoles, and triazoles to provide products with nitrogen incorporated at different sites. Alkyne and diazoketone coupling partners give azolopyridines with various substitution patterns. In addition, 1,4,2-dioxazolone coupling partners yield azolopyrimidines. Furthermore, the mechanisms for the reactions are discussed and the utility of the developed approach is demonstrated by iterative application of C-H functionalization for the rapid synthesis of a patented drug candidate.
首次通过过渡金属催化的 C-烯基唑的 C-H 功能化，合成具有环连接氮原子的稠合[5,6]-双环杂环。几种反应应用于烯基咪唑、吡唑和三唑，以提供在不同位置掺入氮的产物。炔烃和重氮酮偶联试剂提供具有各种取代模式的唑吡啶。此外，1,4,2-二恶唑酮偶联试剂生成唑嘧啶。此外，还讨论了反应的机理，并通过迭代应用 C-H 功能化快速合成专利候选药物，证明了所开发方法的实用性。
