有机三价碘不对称催化合成手性含氟化合物的研究进展

doi:10.6023/cjoc202606029

摘要/Abstract

含氟有机分子在药物和农药等领域有着广泛应用,但自然界中天然存在的有机氟化物极为稀少. 碳-氟键的构建本身也面临诸多挑战. 有机三价碘催化通过极性反转策略,将廉价亲核氟源转化为亲电性有机三价碘氟物种,为温和条件下不对称合成手性含氟化合物提供了独特路径. 本文系统梳理了2014年至今有机三价碘催化不对称合成手性含氟化合物的研究进展,以手性单氟化合物、双氟化合物和多氟化合物的合成为框架,依次讨论了羰基α-氟化、烯烃氟环化、苯酚去芳构化氟化、联烯氟化、1,2-二氟化、偕二氟化、1,3-二氟化以及基于含三氟甲基烯烃的氟化反应等转化类型,分析了代表性体系的催化剂设计、对映选择性控制因素和催化机制,总结了该领域在催化剂发展、氧化还原循环和机理认知等方面的现状与挑战,并对未来发展方向进行了展望.

关键词: 有机三价碘, 不对称催化, 亲核氟化, 手性含氟化合物, 极性反转

Organofluorine compounds are widely applied in pharmaceuticals and agrochemicals, yet naturally occurring organic fluorides are extremely rare. Notably, the construction of carbon-fluorine bonds poses considerable challenges. Hypervalent iodine(III) catalysis offers a distinct approach to the asymmetric synthesis of chiral organofluorine compounds under mild conditions by reversing the polarity of inexpensive nucleophilic fluoride sources to generate electrophilic hypervalent iodine(III) fluoride species. This Review systematically summarizes the progress in hypervalent iodine(III)-catalyzed asymmetric synthesis of chiral organofluorine compounds from 2014 to the present, covering the construction of chiral monofluorinated, difluorinated, and polyfluorinated molecules. Representative transformations discussed include carbonyl α-fluorination, olefin fluorocyclization, fluorinative dearomatization of phenols, fluorination of allenes, 1,2-difluorination, gem-difluorination, 1,3-difluorination, and fluorination of CF₃-substituted alkenes. Key aspects of the reported systems, including catalyst design, enantioselectivity control and catalytic mechanisms, are discussed. Finally, current challenges and future directions are highlighted.

Key words: hypervalent iodine(III), asymmetric catalysis, nucleophilic fluorination, chiral organofluorine compounds, umpolung

引用此文

钟晟昱, 史雷. 有机三价碘不对称催化合成手性含氟化合物的研究进展[J]. 有机化学, doi: 10.6023/cjoc202606029.

Zhong Shengyu, Shi Lei. Advances in Asymmetric Synthesis of Chiral Organofluorine Compounds via Hypervalent Iodine Catalysis[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202606029.

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