38936-00-4Relevant academic research and scientific papers
Regio- and Stereoselective Alkenylation of Allenoates with gem-Difluoroalkenes: Facile Access to Fluorinated 1,4-Enynes Bearing an All-Carbon Quaternary Center
Zhang, Qi-Qi,Chen, Shi-Yong,Lin,Wang, Honggen,Li, Qingjiang
, p. 3123 - 3126 (2019)
A regio- and stereoselective synthesis of fluorinated 1,4-enynes bearing an all-carbon quaternary center at the propargylic position is developed. The synthesis starts from readily available allenoates and gem-difluoroalkenes and proceeds via a key alkyny
Stereoselective formation of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem?difluoroalkenes with lithium organoborates
Huang, Weichen,Shen, Qilong,Xiao, Yisa
supporting information, (2022/02/02)
A method for stereoselective construction of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem?difluoroalkenes in mild conditions was described. The combination of lithium organoborate and ZnBr2 generated in situ lithium ar
Asymmetric Synthesis of 2,2-Difluorotetrahydrofurans through Palladium-Catalyzed Formal [3+2] Cycloaddition
Liu, Jun,Yu, Longhui,Zhao, Gang,Zheng, Changwu
supporting information, p. 23641 - 23645 (2021/10/05)
The asymmetric synthesis of 2,2-difluorinated tetrahydrofurans was accomplished via enantioselective formal [3+2] cycloaddition catalyzed by palladium. The asymmetric reaction between gem-difluoroalkenes and racemic vinyl epoxides or vinylethylene carbonates resulted in the formation of enantioenriched 2,2-difluorotetrahydrofurans with an enantioselectivity up to 98 %. Notably, the reaction used the readily available (R)-BINAP as the ligand at a low loading and yielded a wide variety of difluorinated products in moderate to high yields. Both chiral diastereomers could be obtained in a single sequence.
Acid-Catalyzed Hydrothiolation of gem-Difluorostyrenes to Access α,α-Difluoroalkylthioethers
Sorrentino, Jacob P.,Orsi, Douglas L.,Altman, Ryan A.
, p. 2297 - 2311 (2021/02/06)
The substitution of hydrogen atoms with fluorine in bioactive molecules can greatly impact physicochemical, pharmacokinetic, and pharmacodynamic properties. However, current synthetic methods cannot readily access many fluorinated motifs, which impedes utilization of these groups. Thus, the development of new methods to introduce fluorinated functional groups is critical for developing the next generation of biological probes and therapeutic agents. The synthesis of one such substructure, the α,α-difluoroalkylthioether, typically requires specialized conditions that necessitate early-stage installation. A late-stage and convergent approach to access α,α-difluoroalkylthioethers could involve nucleophilic addition of thiols across gem-difluorostyrenes. Unfortunately, under basic conditions, nucleophilic addition to gem-difluorostyrenes generates an anionic intermediate that can undergo facile elimination of fluoride to generate α-fluorovinylthioethers. To overcome this decomposition, we herein exploit an acid-based catalyst system to facilitate simultaneous nucleophilic addition and protonation of the unstable intermediate. Ultimately, the optimized mild conditions afford the desired α,α-difluoroalkylthioethers in high selectivity and moderate to excellent yields. These α,α-difluoroalkylthioethers are less nucleophilic and more oxidatively stable relative to nonfluorinated thioethers, suggesting the potential application of this unexplored functional group in biological probes and therapeutic agents.
Design and Synthesis of TY-Phos and Application in Palladium-Catalyzed Enantioselective Fluoroarylation of gem-Difluoroalkenes
Li, Zhiming,Lin, Tao-Yan,Liu, Yu,Pan, Zhangjin,Tu, Youshao,Wu, Hai-Hong,Zhang, Junliang,Zhu, Shuai
supporting information, p. 22957 - 22962 (2020/10/19)
The first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine (Sadphos) type ligand TY-Phos. N-Me-TY-Phos can be easily synthesized on a gram scale from readily available starting materials in three steps. Salient features of this work including readily available starting materials, good yields, high enantioselectivities as well as broad substrate scope make this approach very practical and attractive. Notably, the asymmetric synthesis of an analogue of a biologically active molecule is also reported.
Autocatalytic Synthesis of Thioesters via Thiocarbonylation of gem-Difluoroalkenes
Jiang, Xinpeng,Wang, Guan,Zheng, Zicong,Yu, Xiaohui,Hong, Ye,Xia, Haoqi,Yu, Chuanming
supporting information, p. 9762 - 9766 (2020/12/21)
Herein, we report a new method for the synthesis of acyethanethioates via thiocarbonylation of gem-difluoroalkenes with thiols. This reaction provides a new pathway to prepare thioesters under mild conditions without the use of any additives. Mechanistic
Cobalt-Catalyzed Selective Unsymmetrical Dioxidation of gem-Difluoroalkenes
Altman, Ryan A.,Douglas, Justin T.,Orsi, Douglas L.,Sorrentino, Jacob P.
, p. 10451 - 10465 (2020/09/23)
gem-Difluoroalkenes represent valuable synthetic handles for organofluorine chemistry; however, most reactions of this substructure proceed through reactive intermediates prone to eliminate a fluorine atom and generate monofluorinated products. Taking advantage of the distinct reactivity of gem-difluoroalkenes, we present a cobalt-catalyzed regioselective unsymmetrical dioxygenation of gem-difluoroalkenes using phenols and molecular oxygen, which retains both fluorine atoms and provides β-phenoxy-β,β-difluorobenzyl alcohols. Mechanistic studies suggest that the reaction operates through a radical chain process initiated by Co(II)/O2/phenol and quenched by the Co-based catalyst. This mechanism enables the retention of both fluorine atoms, which contrasts most transition-metal-catalyzed reactions of gem-difluoroalkenes that typically involve defluorination.
Photoredox-Coupled F-Nucleophilic Addition: Allylation of gem-Difluoroalkenes
Liu, Haidong,Ge, Liang,Wang, Ding-Xing,Chen, Nan,Feng, Chao
supporting information, p. 3918 - 3922 (2019/02/19)
A novel strategy for the expedient construction of CF3-embeded tertiary/quarternary carbon centers was developed by taking advantage of photoredox catalysis. Thanks to a key step of single-electron oxidation, electron-rich gem-difluoroalkenes, which otherwise are essentially reluctant towards F-nucleoplilic addition, now readily participate in this fluoroallylation reaction. Furthermore, this strategy provides an elegant example for the generation, as well as functionalization, of α-CF3-substituted benzylic radical intermediates using cheap and readily available starting materials.
Organocatalytic Nucleophilic Substitution Reaction of gem-Difluoroalkenes with Ketene Silyl Acetals
Kondoh, Azusa,Koda, Kazumi,Terada, Masahiro
supporting information, p. 2277 - 2280 (2019/03/26)
An organocatalytic nucleophilic substitution reaction of gem-difluoroalkenes with ketene silyl acetals was developed. Phosphazene P4-tBu effectively catalyzed the reaction under mild conditions to provide monofluoroalkenes possessing an alkoxycarbonylmethyl group in high yields with high Z selectivities.
Trifluoromethylation and Monofluoroalkenylation of Alkenes through Radical–Radical Cross-Coupling
Wang, Qiang,Qu, Yi,Tian, Hao,Liu, Yuxiu,Song, Hongjian,Wang, Qingmin
supporting information, p. 8686 - 8690 (2019/06/17)
The first visible-light-induced trifluoromethylation and monofluoroalkenylation of simple alkenes via a challenging radical–radical cross-coupling step was achieved. This method provided a mild, step-economical and redox-neutral route to privileged two different fluorinated difunctionalized allyl compounds. The utility of this method is illustrated by late-stage modification of medically important molecules.
