立体选择性
化学
部分
有机催化
立体化学
烯烃
催化作用
戒指(化学)
布朗斯特德-洛瑞酸碱理论
组合化学
对映选择合成
有机化学
作者
Keith Livingstone,Kathrin Siebold,Stephanie Meyer,Víctor Martín‐Heras,Constantin G. Daniliuc,Ryan Gilmour
出处
期刊:ACS Catalysis
日期:2022-11-10
卷期号:12 (23): 14507-14516
被引量:24
标识
DOI:10.1021/acscatal.2c04511
摘要
The clinical success of α,α-difluorocyclopropanes, combined with limitations in the existing synthesis portfolio, inspired the development of an operationally simple, organocatalysis-based strategy to access cis-configured derivatives with high levels of stereoselectivity (up to >20:1 cis:trans). Leveraging an I(I)/I(III)-catalysis platform in the presence of an inexpensive HF source, it has been possible to exploit disubstituted bicyclobutanes (BCBs) as masked cyclobutene equivalents for this purpose. In situ generation of this strained alkene, enabled by Brønsted acid activation, facilitates an unprecedented 4 → 3 fluorinative ring contraction, to furnish cis-α,α-difluorinated cyclopropanes in a highly stereoselective manner (up to 88% yield). Mechanistic studies are disclosed together with conformational analysis (X-ray crystallography and NMR) to validate cis-α,α-difluorocyclopropanes as isosteres of the 1,4-dicarbonyl moiety. Given the importance of this unit in biology and the foundational no → π* interactions that manifest themselves in this conformation (e.g., collagen), it is envisaged that the title motif will find application in focused molecular design.
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