南京大学王毅Sci. China Chem.:镍催化自由基氟磺酰基-烷基化反应合成不同结构的磺酰氟化合物

摘要：

Sulfonyl fluorides are key components in the fields of Sulfur (VI) fluoride exchange (SuFEx) click chemistry, chemical biology, materials science and drug discovery. A lot of research has recently focused on the synthesis of β-substituted sulfonyl fluorides which can be used as valuable linkers and key intermediates in organic synthesis. However, the synthesis of α-substituted sulfonyl fluoride compounds which can undergo extensive post-functionalization, have received little attention. Existing methods for constructing α-substituted sulfonyl fluoride compounds have primarily focused on the functionalization of α-fluorosulfonyl C(sp2)-X (X = Cl, Br, I…) bonds. The activation of α-fluorosulfonyl C(sp3)-X (X = Cl, Br, I…) bonds, particularly transition-metal-catalyzed cross-coupling reactions involving α-halogen alkyl sulfonyl fluorides to access structurally diverse sulfonyl fluorides is greatly challenging and thus remains unexplored. Along this line, we provide the solutions for nickel-catalyzed radical fluorosulfonyl-alkylation of aryl boronic acids and nickel-catalyzed cascade radical reactions between α-bromo alkyl sulfonyl fluorides and unactivated alkenes, which can obtain structurally diverse sulfonyl fluorides.

研究背景：

图1. 研究背景及本策略（图片来源于Sci. China Chem.）

研究内容：

图2. 条件优化（图片来源于Sci. China Chem.）

图3. 自由基氟磺酰基-烷基化反应底物拓展（图片来源于Sci. China Chem.）

图4. 串联自由基反应合成氟磺酰基官能团化的四氢化萘化合物（图片来源于Sci. China Chem.）

图5. 合成应用和机理研究（图片来源于Sci. China Chem.）

图6. 可能的反应机理（图片来源于Sci. China Chem.）

总结：

In summary, we have developed novel radical fluorosulfonyl-alkylation of aryl boronic acids and the cascade radical reactions involving fluorosulfonylalkyl radicals using nickel catalysis. These new transformations enabled the synthesis of structurally diverse sulfonyl fluorides with high efficiency. The late-stage functionalization of complex bioactive molecules illustrates the potential application value in drug discovery. Mechanistic investigations indicated that a fluorosulfonylalkyl radical is involved in the catalytic cycle. Further study of this technology is underway in our laboratory.

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