Article
Chemistry, Organic
Lin Zhu, Jie Huang, Fanling Meng, Ziyun Tan, Xiao Meng, Yang Xiao, Lanlan Zhang, Wenyi Li, Chao Wang
Summary: A NiH-catalyzed migratory and non-migratory gem-difluoroallylation reaction of alkenyl amines with trifluoromethyl alkenes has been developed. This reaction offers high selectivity and diversity for the synthesis of fluoro-containing amines, which is beneficial for drug discovery.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Bin Wang, Cui-Tian Wang, Xue-Song Li, Xue-Yuan Liu, Yong-Min Liang
Summary: Here, we report a novel and efficient photoredox catalytic radical addition/defluoroalkylation coupling reaction between primary amines and trifluoromethyl-substituted alkenes. A series of gem-difluoroalkenes were synthesized through C-N bond cleavage of α-3°, α-2°, and α-1° amines under visible light irradiation. This reaction exhibits a broad substrate scope and excellent functional group tolerance.
Article
Chemistry, Multidisciplinary
Bin Zhao, Zichen Pan, Jiayu Pan, Hongping Deng, Xiaoli Bu, Mengtao Ma, Fei Xue
Summary: We report a regiodivergent defluorinative carboxylation of gem-difluorocyclopropanes achieved by subtly modulating the electrochemical conditions. This method allows for the selective synthesis of branched and linear monofluoroalkene carboxylic acids in moderate to high yields and with exclusive regioselectivities. The protocol is green, using atmospheric CO2 as the C1 source and not requiring transition metals, and can be scaled up and applied to late-stage functionalization of complex compounds.
Article
Chemistry, Organic
Andrew J. Intelli, Ryan T. Lee, Ryan A. Altman
Summary: The installation of fluorine and fluorinated functional groups into drug-like scaffolds can greatly affect the properties of compounds. However, current synthetic methods are limited in their ability to incorporate certain potentially useful fluorinated substructures, such as the α,α-difluorophosphine oxide. This study presents a new approach using peroxide-initiated hydrophosphinylation reactions to prepare a wide range of α,α-difluorophosphine oxides and functions, utilizing readily available reagents and green solvents.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Grace A. Lutovsky, Samuel N. Gockel, Mark W. Bundesmann, Scott W. Bagley, Tehshik P. Yoon
Summary: In this study, a direct decarboxylative cross-coupling of native carboxylic acids with nucleophilic coupling partners mediated by inexpensive and non-toxic Fe(III) salts was reported. This method involves an initial photochemical decarboxylation followed by radical-polar crossover, enabling the construction of diverse carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds with remarkable generality.
Article
Chemistry, Multidisciplinary
Jie Xu, Jiangjun Liu, Gang Chen, Baojian Xiong, Xuemei Zhang, Zhong Lian
Summary: An efficient method for accessing gem-difluoro-2-trifluromethyl styrene derivatives via palladium catalysis has been presented. This method offers mild reaction conditions, broad substrate scope, and good product yields. Additionally, gram-scale reactions have demonstrated the robustness and potential of this method. Control experiments have shown that the -CF3 group is essential for the success of this transformation. Finally, the practicality of this method has been successfully proven through three synthetic applications.
Article
Chemistry, Organic
Chen-Lin Cao, Guang-Xu Zhang, Fei Xue, Hong-Ping Deng
Summary: A new method for the mild monofluoroalkenylation of C-H bonds using gem-difluoroalkenes was developed by synergistic merger of photoredox and bromine-based hydrogen atom transfer catalysis. This approach allows for the efficient synthesis of multisubstituted monofluoroalkenes from a wide range of C-H patterns and can be accelerated in a continuous-flow protocol, demonstrating the ability to access valuable complex molecules selectively. Preliminary mechanistic experiments suggest a radical-radical cross-coupling mechanism in the reaction.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Xiao-Yu Lu, Ang Gao, Meng-Yuan Ge, Ze-Jie Xia, Qi-Le Liu, Ting-Hua Tao, Xiao-Mei Sun
Summary: A new strategy for synthesizing monofluoroalkenes using α-fluoroacrylic acids and N-hydroxyphthalimide (NHPI) redox-active esters as coupling partners is developed. This decarboxylative reaction enables the formation of C(sp2)-C(sp3) bonds, providing a practical and efficient approach for constructing various monofluoroalkenes with excellent functional group compatibility and Z-stereoselectivity. Furthermore, this work also serves as a platform for modifying complex biologically active molecules containing carboxylic acids.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Wan-Qiang Yuan, Yu-Tao Liu, Yu-Qing Ni, Yong-Ze Liu, Fei Pan
Summary: An efficient and transition-metal-free photocatalytic trifluoromethylation-gem-difluoroallylation reaction of unactivated alkenes has been developed. This protocol utilizes manageable Langlois' reagent as the CF3 radical source and alpha-trifluoromethyl alkene as the gem-difluoroalkenyl source in the presence of Fukuzumi acridinium salts as a photocatalyst. The reaction proceeds under mild conditions and provides diverse trifluoromethyl-substituted gem-difluoroalkenes in moderate to good yields.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Linzi Wen, Boao Li, Ziyan Zou, Naifu Zhou, Chengbo Sun, Pengju Feng, Hongsheng Li
Summary: In this study, a direct electrolysis protocol was demonstrated for the chemo- and regio-selective difluorination, azo-fluorination, and fluoro-alkoxylation of gem-difluorostyrenes under mild conditions. The reaction allowed for the selective synthesis of a distinct type of long-chain perfluoroalkyl aromatics involving Et3N3HF as the fluorine source with/without other nucleophiles. The reaction exhibited good functional group tolerance and was amenable to gram-scale synthesis. Moreover, an electrochemical reduction of the benzyl C-F bond was also achieved.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Zichen Pan, Xiuqi Wang, Shuaishuai Zhao, Hongping Deng, Mengtao Ma, Fei Xue
Summary: We have successfully developed a convergent paired electrolysis strategy for defluorinative thiolation using thiols and gem-difluoroalkenes as precursors. This protocol shows excellent tolerance towards a wide range of functional groups, demonstrated by successful late-stage defluorothiolation of complex molecules. Additionally, this strategy enables gram-scale synthesis by efficiently utilizing both anodic oxidation and cathodic reduction processes.
Article
Chemistry, Organic
Xiao-Yu Lu, Meng-Yuan Ge, Ting-Hua Tao, Xiao-Mei Sun, Meng-Ting Gao, Shu-Ting Bao, Qi-Le Liu, Ze-Jie Xia, Jing Xia
Summary: This study presents a novel and practical strategy for constructing monofluoroalkenes from aliphatic aldehydes, which are key functional groups in synthetic transformations in pharmaceutical and agrochemical sciences. The reaction showed excellent Z-stereoselectivity with moderate to high yields using alpha-fluoro cinnamic acids and aliphatic aldehydes as substrates.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Wei Tang, Pei Fan
Summary: A nickel-catalyzed regioselective cross-electrophilic ring opening reaction of sulfonyl-protected aziridines with trifluoromethyl-substituted alkenes has been reported, providing a new and efficient entry to prepare gem-difluorobishomoallylic sulfonamides. Moreover, the scaffold of 6-fluoro-1,2,3,4-tetrahydropyridine can be constructed starting from the ring opening products via NaH-mediated intramolecular defluorinative nucleophilic vinylic substitution.
Article
Chemistry, Physical
Baojian Xiong, Xuemeng Chen, Jiangjun Liu, Xuemei Zhang, Ying Xia, Zhong Lian
Summary: A cross-electrophile coupling between gem-difluorinated cyclopropanes and 2,2-difluorovinyl tosylate is achieved via dual Ni/Pd cooperative catalysis, leading to structurally unique organofluorine compounds with high (Z)-selectivity and good yields. The practical utility of this method is demonstrated by the late-stage modification of a series of complex bioactive molecules.
Article
Chemistry, Organic
Qing Wang, Ling Yue, Yanyang Bao, Yanan Wang, Danni Kang, Yan Gao, Zheliang Yuan
Summary: In this work, a photoredox-catalyzed gem-difluoroallylation was reported for the construction of all-carbon quaternary centers using oxalates as activating groups for tertiary alcohols. Efficient tertiary radical addition to alpha-trifluoromethyl alkenes enabled the formation of these challenging structures. The method showed good functional group tolerance for both alpha-trifluoromethyl alkenes and oxalates, and was successfully applied to the synthesis of monofluoralkenes.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
