Oxidative β-C–H Sulfonylation of Cyclic Amines
R. J. Griffiths, W. C. Kong, S. A. Richards, G. A. Burley, M. C. Willis, E. P. A. Talbot*
GlaxoSmithKline Medicines Research, University of Strathclyde, University of Oxford
—Chem.Sci. 9, 2295–2300 (2018).
Recommended by Ying Zhang_MOC
KEY WORDS: C–H bond functionalization; β-sulfonylation; metal-free; cyclic amines
ABSTRACT: A transition metal-free strategy for the dehydrogenative β-sulfonylation of tertiary cyclic amines is described. N-iodosuccinimide facilitates regioselective oxidative sulfonylation at C–H bonds positioned β to the nitrogen atom of tertiary amines, installing enaminyl sulfone functionality in cyclic systems. Mild reaction conditions, broad functional group tolerance and a wide substrate scope are demonstrated. The nucleophilic character of the enaminyl sulfone is harnessed, demonstrating potential application for scaffold diversification.
Cyclic enaminyl sulfones as templates for synthesis. Tol = para-tolyl.
Summary and Comments:
In conclusion, the authors have developed a straightforward process for the β-C–H functionalization of piperidines. The reactions combine piperidines and sodium sulfinates, under the action of NIS, to provide enaminyl sulfone products. The process is achieved under mild conditions, and shows good functional group tolerance. The authors also establish that the resultant cyclic enaminyl sulfones are versatile templates for further elaboration. The authors envisage that this approach will expedite the generation of diverse compound libraries for use in drug discovery.
作者為哌啶的β-C–H官能化開發了一種簡單的方法。在NIS的作用下將哌啶和亞硫酸鈉混合，以提供烯氨碸產物。該過程在溫和的條件下完成，並顯示出良好的官能團耐受性。可以將所得的環狀烯胺碸作為通用的模板，用於進一步修飾。這種方法將加快用於藥物發現的各種化合物庫的生成。