Scheidt Felix, Thiehoff Christian, Yilmaz Gülay, Meyer Stephanie, Daniliuc Constantin G, Kehr Gerald, Gilmour Ryan
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany.
Beilstein J Org Chem. 2018 May 9;14:1021-1027. doi: 10.3762/bjoc.14.88. eCollection 2018.
Herein, we describe a catalytic fluorooxygenation of readily accessible -allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp)-F bond of the mono-fluoromethyl unit and the C(sp)-O bond of the ring are aligned in a relationship thereby engaging in stabilising hyperconjugative interactions with , electron-rich σ-bonds (σ→σ* and σ→σ*). This manifestation of the stereoelectronic effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.
在此，我们描述了一种通过I(I)/I(III)体系对易于获得的烯丙基羧酰胺进行催化氟氧化反应，以生成含氟甲基的2-恶唑啉。催化作用取决于Selectfluor的氧化能力，而HF既作为氟源又作为布朗斯特酸活化剂。单氟甲基单元的C(sp)-F键和环的C(sp)-O键呈特定关系排列，从而与富电子的σ键（σ→σ和σ→σ）形成稳定的超共轭相互作用。通过对一个代表性实例的X射线晶体学分析确定了这种立体电子效应的表现。鉴于氟在药物发现中的重要性、其调节构象的能力以及自然界中2-恶唑啉骨架的普遍性，该策略为快速进入一类重要的生物电子等排体提供了途径。
