Monofluoromethylation of acyl chlorides and chloroformates employing fluorobis(phenylsulfonyl)methane. Synthesis of monofluoromethyl ketones via selective zinc-mediated reductive desulfonylation†‡

IF 4.7 1区化学 Q1 CHEMISTRY, ORGANIC Organic Chemistry Frontiers Pub Date : 2025-04-14 DOI:10.1039/D5QO00451A

Alexander Knieb, Thomas Saal, Prabodh Rao, Xanath Ispizua-Rodriguez and G. K. Surya Prakash

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Abstract

A high yielding protocol for the synthesis of valuable monofluoromethyl ketones (MFMK) utilizing fluorobis(phenylsulfonyl)methane (FBSM) is presented. The protocol allows the incorporation of the biologically relevant monofluoromethyl group under mild reaction conditions and in short reaction times. The obtained fluorobis(phenylsulfonyl)methyl ketones can subsequently be selectively reduced to the fluoro(phenylsulfonyl)methyl- and subsequently to monofluoromethyl ketones via zinc-mediated reductive desulfonylation. Furthermore, weak intramolecular van der Waals interactions were observed in fluorobis(phenylsulfonyl)methyl ketones and they were further investigated using nuclear magnetic resonance spectroscopy and single crystal X-ray diffraction analysis. An improved method for the assessment of lipophilic properties of these fluorinated small molecules has been developed and correlated to theoretical log P values.

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利用含氟（苯基磺酰）甲烷对酰氯和氯甲酸盐进行单氟甲基化。选择性锌介导的还原性脱硫法合成单氟甲基酮

介绍了一种利用氟（苯基磺酰）甲烷（FBSM）合成有价单氟甲基酮（MFMK）的高产方案。该议定书允许在温和的反应条件和较短的反应时间内掺入具有生物学意义的单氟甲基。所得的含氟（苯磺酰基）甲基酮随后可通过锌介导的还原性脱硫选择性还原为含氟（苯磺酰基）甲基酮，随后又可选择性还原为单氟甲基酮。此外，在含氟（苯基磺酰基）甲基酮中观察到弱分子内范德华相互作用，并利用核磁共振波谱和单晶x射线衍射分析对其进行了进一步研究。开发了一种改进的方法来评估这些氟化小分子的亲脂性，并与理论对数P值相关联。

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来源期刊

Organic Chemistry Frontiers CHEMISTRY, ORGANIC-

CiteScore

7.90

自引率

11.10%

发文量

686

审稿时长

1 months

期刊介绍： Organic Chemistry Frontiers is an esteemed journal that publishes high-quality research across the field of organic chemistry. It places a significant emphasis on studies that contribute substantially to the field by introducing new or significantly improved protocols and methodologies. The journal covers a wide array of topics which include, but are not limited to, organic synthesis, the development of synthetic methodologies, catalysis, natural products, functional organic materials, supramolecular and macromolecular chemistry, as well as physical and computational organic chemistry.