Pub Date : 2025-11-01DOI: 10.1016/j.jfluchem.2025.110506
Yanbo Yu , Anil Kumar Soda , Christopher Bognar , Gregory G. Gaehle , Stephen M. Moerlein , Michael L. Nickels , Jagan Rajamoni , Joel S. Perlmutter , Zhude Tu
The vesicular acetylcholine transporter (VAChT), primarily located in presynaptic cholinergic nerve terminals, serves as a key target in neuroimaging studies and neuropathological assessments to quantify cholinergic neuron decline. [18F]VAT has been demonstrated as a selective and specific radiotracer to quantify VAChT expression in the brains of patients with neurological diseases. Herein, we report the absolute configuration of the chemical structure and development of a straightforward cGMP protocol to produce[18F]VAT for clinical use. The absolute configuration was unambiguously determined by X-ray crystallography of the VAT phenolic analogue, establishing its (2R,3R) stereochemistry for the first time. The radiotracer production was successfully accomplished using a simple one-pot and one-step approach under cGMP conditions, achieving an average radiochemical yield of 16.9% ± 1.8% (decay-corrected to the end of synthesis), a molar activity of 61.9 ± 19.6% GBq /μmol, with a total synthesis time of approximately 60 min (n = 3). The final product met all established quality control criteria for human use.
囊泡性乙酰胆碱转运蛋白（VAChT）主要位于突触前胆碱能神经末梢，是神经影像学研究和神经病理学评估中量化胆碱能神经元衰退的关键靶点。[18F]VAT已被证明是一种选择性和特异性的放射性示踪剂，可量化神经系统疾病患者大脑中VAChT的表达。在本文中，我们报告了化学结构的绝对构型，并开发了一种简单的cGMP方案来生产用于临床使用的[18F]VAT。用x射线晶体学方法确定了VAT酚类似物的绝对构型，首次建立了它的（2R,3R）立体化学。在cGMP条件下，采用简单的一锅一步法成功地完成了放射性示踪剂的生产，平均放射化学产率为16.9%±1.8%（衰变校正到合成结束），摩尔活性为61.9±19.6% GBq /μmol，总合成时间约为60 min （n = 3）。最终产品符合人类使用的所有既定质量控制标准。
{"title":"Absolute configuration and an improved automated cGMP production of a clinically promising radiotracer for imaging VAChT","authors":"Yanbo Yu , Anil Kumar Soda , Christopher Bognar , Gregory G. Gaehle , Stephen M. Moerlein , Michael L. Nickels , Jagan Rajamoni , Joel S. Perlmutter , Zhude Tu","doi":"10.1016/j.jfluchem.2025.110506","DOIUrl":"10.1016/j.jfluchem.2025.110506","url":null,"abstract":"<div><div>The vesicular acetylcholine transporter (VAChT), primarily located in presynaptic cholinergic nerve terminals, serves as a key target in neuroimaging studies and neuropathological assessments to quantify cholinergic neuron decline. [<sup>18</sup>F]VAT has been demonstrated as a selective and specific radiotracer to quantify VAChT expression in the brains of patients with neurological diseases. Herein, we report the absolute configuration of the chemical structure and development of a straightforward cGMP protocol to produce[<sup>18</sup>F]VAT for clinical use. The absolute configuration was unambiguously determined by X-ray crystallography of the VAT phenolic analogue, establishing its (<em>2R,3R</em>) stereochemistry for the first time. The radiotracer production was successfully accomplished using a simple one-pot and one-step approach under cGMP conditions, achieving an average radiochemical yield of 16.9% ± 1.8% (decay-corrected to the end of synthesis), a molar activity of 61.9 ± 19.6% GBq /μmol, with a total synthesis time of approximately 60 min (<em>n</em> = 3). The final product met all established quality control criteria for human use.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"288 ","pages":"Article 110506"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fluorine gas (F₂) is indispensable in industries ranging from fluoropolymer synthesis to semiconductor fabrication, but its high toxicity, extreme reactivity, and storage hazards limit its applicability. On-demand in situ production could eliminate the need for bulk storage and transport. Here, we demonstrate fluorine generation from CF₄ using a Tesla coil–based 2 MHz cold atmospheric plasma (CAP) device. Plasma was generated with Ar (Case I), Ar + CF₄ (Case II), and Ar + CF₄ + O₂ (Case III). Optical emission spectroscopy (OES) and direct gas sensing used to detect species. Adding O₂ increased F₂ emission while reducing CF, CF₂, and C₂ bands, and simultaneously decreased stainless steel electrode erosion. The oxygen effect is attributed to carbon scavenging and oxide film formation, enhancing F₂ yield while protecting electrodes. These findings establish the feasibility of plasma-based, switch-on/switch-off fluorine production.
{"title":"Feasibility of on-demand fluorine generation using cold atmospheric plasma from benign precursor: An optical emission spectroscopy study","authors":"Rajib Kar , Vishakha Bende , Vanita Sekar , R.L. Bhardwaj , J.P. Nilaya , M.L. Mascarenhas","doi":"10.1016/j.jfluchem.2025.110500","DOIUrl":"10.1016/j.jfluchem.2025.110500","url":null,"abstract":"<div><div>Fluorine gas (F₂) is indispensable in industries ranging from fluoropolymer synthesis to semiconductor fabrication, but its high toxicity, extreme reactivity, and storage hazards limit its applicability. On-demand in situ production could eliminate the need for bulk storage and transport. Here, we demonstrate fluorine generation from CF₄ using a Tesla coil–based 2 MHz cold atmospheric plasma (CAP) device. Plasma was generated with Ar (Case I), Ar + CF₄ (Case II), and Ar + CF₄ + <em>O</em>₂ (Case III). Optical emission spectroscopy (OES) and direct gas sensing used to detect species. Adding O₂ increased F₂ emission while reducing CF, CF₂, and C₂ bands, and simultaneously decreased stainless steel electrode erosion. The oxygen effect is attributed to carbon scavenging and oxide film formation, enhancing F₂ yield while protecting electrodes. These findings establish the feasibility of plasma-based, switch-on/switch-off fluorine production.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"288 ","pages":"Article 110500"},"PeriodicalIF":1.9,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145374605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jfluchem.2025.110485
Sujun Wei, Francisco Caban , Jiayi Xue , Feruza Turobova
4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (aka BODIPY) derivatives are typically air stable, highly fluorescent with high quantum yield, low toxicity and high biocompatibility, which attract strong interest as fluorescent markers and dyes in biological research field. Herein we report a novel synthetic strategy to convert a stable dipyrrole intermediate to a BODIPY dye with a fluorene unit at its meso position. More interestingly the covalent C-C single bond is between BODIPY and fluorene’s sole sp3 hybridized carbon, which provides bulkiness around BODIPY aromatic core to reduce intermolecular π−π stacking. This new BODIPY compound is fully characterized, and its X-ray crystal structure is reported. We also extend this methodology to produce chloro substituted analog.
{"title":"New synthesis of meso-substituted 4,4-Difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) with fluorene","authors":"Sujun Wei, Francisco Caban , Jiayi Xue , Feruza Turobova","doi":"10.1016/j.jfluchem.2025.110485","DOIUrl":"10.1016/j.jfluchem.2025.110485","url":null,"abstract":"<div><div>4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (aka BODIPY) derivatives are typically air stable, highly fluorescent with high quantum yield, low toxicity and high biocompatibility, which attract strong interest as fluorescent markers and dyes in biological research field. Herein we report a novel synthetic strategy to convert a stable dipyrrole intermediate to a BODIPY dye with a fluorene unit at its meso position. More interestingly the covalent C-C single bond is between BODIPY and fluorene’s sole sp<sup>3</sup> hybridized carbon, which provides bulkiness around BODIPY aromatic core to reduce intermolecular π−π stacking. This new BODIPY compound is fully characterized, and its X-ray crystal structure is reported. We also extend this methodology to produce chloro substituted analog.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"287 ","pages":"Article 110485"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jfluchem.2025.110486
Yi Hu , Hao Yan , Jian Liu , Wensheng Chen , Xiaomeng Zhou
Trifluoroiodomethane (CF₃I), due to its environmental friendliness, has emerged as a promising PFAS-Alternative refrigerant. In practical applications, the compatibility between CF₃I and rubber materials is a critical parameter to ensure its long-term and safe operation in refrigeration systems. Therefore, this study systematically investigates the compatibility of CF₃I with two commonly used sealing elastomers in refrigeration systems—chloroprene rubber (CR) and acrylic rubber (ACM)—under conditions of 25 °C and 0.1 MPa. The elastomers were subjected to comprehensive physical and mechanical property evaluations, including weight, volume, hardness, tensile strength, elongation at break, and crosslinking density, as well as surface morphology analysis, elemental and functional group characterization. Additionally, molecular dynamics (MD) simulations were employed to analyze interfacial interactions. Experimental results revealed notable degradation in mechanical performance and microstructural integrity of both CR rubber and ACM rubber upon exposure to CF₃I. This degradation was primarily attributed to CF₃I-induced swelling and the disruption of chain packing due to non-covalent interactions between CF₃I molecules and polymer chains. MD simulations further showed that CF₃I exhibited a higher diffusion coefficient in ACM (16.53 × 10⁻⁶ cm²/s) compared to CR (7.25 × 10⁻⁶ cm²/s). CF₃I predominantly adsorbs onto polar groups in the rubber matrix (such as C–Cl and C = O) via van der Waals interactions, promoting interfacial accumulation and migration, which may compromise material stability. Integrating experimental and simulation findings, the compatibility of CF₃I with both CR and ACM is concluded to be relatively poor.
{"title":"Compatibility study of PFAS-alternative refrigerant CF₃I with common refrigeration elastomers","authors":"Yi Hu , Hao Yan , Jian Liu , Wensheng Chen , Xiaomeng Zhou","doi":"10.1016/j.jfluchem.2025.110486","DOIUrl":"10.1016/j.jfluchem.2025.110486","url":null,"abstract":"<div><div>Trifluoroiodomethane (CF₃I), due to its environmental friendliness, has emerged as a promising PFAS-Alternative refrigerant. In practical applications, the compatibility between CF₃I and rubber materials is a critical parameter to ensure its long-term and safe operation in refrigeration systems. Therefore, this study systematically investigates the compatibility of CF₃I with two commonly used sealing elastomers in refrigeration systems—chloroprene rubber (CR) and acrylic rubber (ACM)—under conditions of 25 °C and 0.1 MPa. The elastomers were subjected to comprehensive physical and mechanical property evaluations, including weight, volume, hardness, tensile strength, elongation at break, and crosslinking density, as well as surface morphology analysis, elemental and functional group characterization. Additionally, molecular dynamics (MD) simulations were employed to analyze interfacial interactions. Experimental results revealed notable degradation in mechanical performance and microstructural integrity of both CR rubber and ACM rubber upon exposure to CF₃I. This degradation was primarily attributed to CF₃I-induced swelling and the disruption of chain packing due to non-covalent interactions between CF₃I molecules and polymer chains. MD simulations further showed that CF₃I exhibited a higher diffusion coefficient in ACM (16.53 × 10⁻⁶ cm²/s) compared to CR (7.25 × 10⁻⁶ cm²/s). CF₃I predominantly adsorbs onto polar groups in the rubber matrix (such as C–Cl and <em>C</em> = <em>O</em>) via van der Waals interactions, promoting interfacial accumulation and migration, which may compromise material stability. Integrating experimental and simulation findings, the compatibility of CF₃I with both CR and ACM is concluded to be relatively poor.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"287 ","pages":"Article 110486"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145332616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jfluchem.2025.110481
Suming Jing , Zhineng Wang , Keyao Li , Qianxiong Chen , Xuesong Zhang , Wei Zhang , Mingwei Liu
The design and synthesis of high-performance melt-cast explosive carriers are of strategic significance for advancing weapon system technologies. In this study, three fluorinated benzene-based melt-cast explosive carriers—3-fluoro-2,4,6-trinitroanisole (FTNAN), 3-fluoro-2,4,6-trinitrotoluene (FTNT), and 1-fluoro-2,4-dinitro-5-(trifluoromethyl)benzene (TFDNT)—were synthesized using benzene rings as the molecular scaffold, with fluorine atoms and nitro groups serving as energetic modifiers. Structural characterization was systematically conducted through Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (¹H/¹³C NMR), elemental analysis, and differential scanning calorimetry (DSC). Single-crystal X-ray diffraction unambiguously confirmed their molecular configurations. Energetic performance evaluation involved computational modeling using Gaussian 09 (heat of formation calculations) and EXPLO5 (detonation parameter predictions). Experimental and theoretical analyses demonstrated that FTNAN and FTNT exhibit superior properties.
{"title":"Synthesis and characterization of fluorinated benzene-based carriers for melt-cast explosives","authors":"Suming Jing , Zhineng Wang , Keyao Li , Qianxiong Chen , Xuesong Zhang , Wei Zhang , Mingwei Liu","doi":"10.1016/j.jfluchem.2025.110481","DOIUrl":"10.1016/j.jfluchem.2025.110481","url":null,"abstract":"<div><div>The design and synthesis of high-performance melt-cast explosive carriers are of strategic significance for advancing weapon system technologies. In this study, three fluorinated benzene-based melt-cast explosive carriers—3-fluoro-2,4,6-trinitroanisole (FTNAN), 3-fluoro-2,4,6-trinitrotoluene (FTNT), and 1-fluoro-2,4-dinitro-5-(trifluoromethyl)benzene (TFDNT)—were synthesized using benzene rings as the molecular scaffold, with fluorine atoms and nitro groups serving as energetic modifiers. Structural characterization was systematically conducted through Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (¹H/¹³C NMR), elemental analysis, and differential scanning calorimetry (DSC). Single-crystal X-ray diffraction unambiguously confirmed their molecular configurations. Energetic performance evaluation involved computational modeling using Gaussian 09 (heat of formation calculations) and EXPLO5 (detonation parameter predictions). Experimental and theoretical analyses demonstrated that FTNAN and FTNT exhibit superior properties.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"287 ","pages":"Article 110481"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jfluchem.2025.110475
Ahmed Aldulaimi , Shakir Mahmood Saeed , Soumya V Menon , Waam Mohammed Taher , Ruya yilmaz saber , Subhashree Ray , Karthikeyan Jayabalan , Aashna Sinha , Mariem Alwan , Renu Sharma
This review gives an overview of the synthesis of difluoromethyl thioethers through the S-difluoromethylation of corresponding aromatic thiols. The review has been classified based on the type of difluoromethyling agents (i.e., organosulfur-based difluoromethylating agents, organosilicon-based difluoromethylating agents, organophosphorus-based difluoromethylating agents) and surveyed the literature up until the end of 2024.
{"title":"Direct S-difluoromethylation of thiols: A facile synthetic route to difluoromethyl thioethers","authors":"Ahmed Aldulaimi , Shakir Mahmood Saeed , Soumya V Menon , Waam Mohammed Taher , Ruya yilmaz saber , Subhashree Ray , Karthikeyan Jayabalan , Aashna Sinha , Mariem Alwan , Renu Sharma","doi":"10.1016/j.jfluchem.2025.110475","DOIUrl":"10.1016/j.jfluchem.2025.110475","url":null,"abstract":"<div><div>This review gives an overview of the synthesis of difluoromethyl thioethers through the <em>S</em>-difluoromethylation of corresponding aromatic thiols. The review has been classified based on the type of difluoromethyling agents (<em>i.e</em>., organosulfur-based difluoromethylating agents, organosilicon-based difluoromethylating agents, organophosphorus-based difluoromethylating agents) and surveyed the literature up until the end of 2024.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"287 ","pages":"Article 110475"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jfluchem.2025.110483
Viktor G. Makotchenko , Alexander M. Panich , Ekaterina D. Grayfer
Fluorinated graphitic materials are widely studied for various applications including energy storage, lubricants, hydrophobic coatings, neutron reflectors, etc. Here, we investigate the F2 gas fluorination of three starting graphitic materials with different thicknesses: graphite, multi-layer graphene, and “graphene paper”. All synthesized products exhibit similar interplanar spacings, FTIR and XPS spectral characteristics, and similar compositions corresponding to graphite monofluoride CF1.12. However, the thickness of the starting compound affects the temperature required for the fluorination and the decomposition temperatures of the resulting fluorides. Fluorinated graphite CF1.12 prepared from graphite is stable up to 600 °C, while the stability drops dramatically for the fluorinated multi-layer graphene, which starts decomposing already at 100 °C. Besides, few-layer CF1.12 forms stable colloidal dispersions in organic media, unlike its thicker counterpart. The obtained results will facilitate structural engineering of fluorinated nanographite materials to optimize their properties for potential applications.
{"title":"Effect of graphene stack thickness on gaseous fluorination of graphitic materials","authors":"Viktor G. Makotchenko , Alexander M. Panich , Ekaterina D. Grayfer","doi":"10.1016/j.jfluchem.2025.110483","DOIUrl":"10.1016/j.jfluchem.2025.110483","url":null,"abstract":"<div><div>Fluorinated graphitic materials are widely studied for various applications including energy storage, lubricants, hydrophobic coatings, neutron reflectors, etc. Here, we investigate the F<sub>2</sub> gas fluorination of three starting graphitic materials with different thicknesses: graphite, multi-layer graphene, and “graphene paper”. All synthesized products exhibit similar interplanar spacings, FTIR and XPS spectral characteristics, and similar compositions corresponding to graphite monofluoride CF<sub>1.12</sub>. However, the thickness of the starting compound affects the temperature required for the fluorination and the decomposition temperatures of the resulting fluorides. Fluorinated graphite CF<sub>1.12</sub> prepared from graphite is stable up to 600 °C, while the stability drops dramatically for the fluorinated multi-layer graphene, which starts decomposing already at 100 °C. Besides, few-layer CF<sub>1.12</sub> forms stable colloidal dispersions in organic media, unlike its thicker counterpart. The obtained results will facilitate structural engineering of fluorinated nanographite materials to optimize their properties for potential applications.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"287 ","pages":"Article 110483"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jfluchem.2025.110484
Olena Voloshyna , Bohdan Moroz , Kostiantyn P. Melnykov , Serhii Holovach , Dmytro Lesyk , Yuliia Holota , Petro Borysko , Andrey A. Filatov , Oleksandr O. Grygorenko
An expedient gram-scale synthesis of stereochemically pure exo- and endo-5,5-difluorooctahydropentalen-2-amines – valuable building blocks for medicinal chemistry – is described. The method commenced from the commercially available Weiss diketone. The compound’s stereochemistry was controlled using diastereoselective NaBH4-mediated reduction and Mitsunobu reaction at the corresponding steps. To install the gem‑difluorinated moiety, classical DAST-mediated deoxofluorination was employed. Physicochemical properties of the synthesized compounds (pKa and LogP) demonstrated their potential for applications in drug discovery as cyclohexane replacements.
{"title":"Gram-scale synthesis and physicochemical properties of exo- and endo-5,5-difluorooctahydropentalen-2-amines","authors":"Olena Voloshyna , Bohdan Moroz , Kostiantyn P. Melnykov , Serhii Holovach , Dmytro Lesyk , Yuliia Holota , Petro Borysko , Andrey A. Filatov , Oleksandr O. Grygorenko","doi":"10.1016/j.jfluchem.2025.110484","DOIUrl":"10.1016/j.jfluchem.2025.110484","url":null,"abstract":"<div><div>An expedient gram-scale synthesis of stereochemically pure exo- and endo-5,5-difluorooctahydropentalen-2-amines – valuable building blocks for medicinal chemistry – is described. The method commenced from the commercially available Weiss diketone. The compound’s stereochemistry was controlled using diastereoselective NaBH<sub>4</sub>-mediated reduction and Mitsunobu reaction at the corresponding steps. To install the gem‑difluorinated moiety, classical DAST-mediated deoxofluorination was employed. Physicochemical properties of the synthesized compounds (pK<sub>a</sub> and LogP) demonstrated their potential for applications in drug discovery as cyclohexane replacements.</div></div>","PeriodicalId":357,"journal":{"name":"Journal of Fluorine Chemistry","volume":"287 ","pages":"Article 110484"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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