28321-09-7Relevant articles and documents
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
-Annulation of gem-Difluoroalkenes and Pyridinium Ylides: Access to Functionalized 2-Fluoroindolizines
Zhang, Jun-Qi,Hu, Dandan,Song, Jinyu,Ren, Hongjun
, p. 4646 - 4660 (2021/04/06)
A [3 + 2]-annulation of gem-difluoroalkenes and pyridinium ylides was developed employing ambient air as the sole oxidant in an open-vessel manner, affording a series of multifunctionalized 2-fluoroindolizines in moderate to good yields. In this reaction, gem-difluoroalkene acts as a C2 synthon and entirely avoids the competitive addition-elimination process, which provides facile access to 2-fluoroindolizines.
Dehalogenative Cross-Coupling of gem-Difluoroalkenes with Alkyl Halides via a Silyl Radical-Mediated Process
Tian, Hao,Yang, Shaoxiang,Wang, Xiaochen,Xu, Wentao,Liu, Yuxiu,Li, Yongqiang,Wang, Qingmin
supporting information, p. 12772 - 12782 (2021/09/13)
Herein, we describe a convenient general protocol for monofluoroalkenylation reactions of alkyl bromides involving cooperative visible-light photoredox catalysis and halogen abstraction. Mechanistic experiments showed that the products were generated by selective cross-coupling of aliphatic radicals with fluoroalkenyl radicals. Silyl radical-mediated halogen abstraction enabled the protocol to be used for the monofluoroalkenylation of a broad range of alkyl and heteroaryl halides. The protocol could be carried out on a gram scale and was applied to cholesterol, indicating its utility for late-stage monofluoroalkenylation reactions.
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
Pd-Catalyzed Selective Carbonylation of gem-Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters
Liu, Jiawang,Yang, Ji,Ferretti, Francesco,Jackstell, Ralf,Beller, Matthias
supporting information, p. 4690 - 4694 (2019/03/13)
The first catalyst for the alkoxycarbonylation of gem-difluoroalkenes is described. This novel catalytic transformation proceeds in the presence of Pd(acac)2/1,2-bis((di-tert-butylphosphan-yl)methyl)benzene (btbpx) (L4) and allows for an efficient and straightforward access to a range of difluoromethylated esters in high yields and regioselectivities. The synthetic utility of the protocol is showcased in the practical synthesis of a Cyclandelate analogue using this methodology as the key step.
Rhodium-Catalyzed Defluorinative Vinylation of gem-Difluoroalkenes for the Synthesis of 2-Fluoro-1,3-dienes
Song, Shengjin,Liu, Huan,Wang, Lu,Zhu, Chuan,Loh, Teck-Peng,Feng, Chao
supporting information, p. 1036 - 1040 (2019/09/16)
Herein, we present a strategy for the formation of 2-fluoro-1,3-diene derivatives via rhodium-catalyzed direct C(sp2)—C(sp2) cross-coupling of gem-difluoroalkenes and acrylamides. By merging Rh(III)-catalyzed C(sp2)–H bond activation and nucleophilic addition/F-elimination of gem-difluoroalkene, an efficient defluorinative vinylation reaction is uncovered, which leads to the generation of 2-fluoro-1,3-dienes in moderate to good yields with excellent stereoselectivity under mild conditions. Preliminary mechanistic study suggests unique effects of fluorine substituents which allow the reactivity profile not observed with the congeners bearing heavier halides.
Coupling of Trifluoroacetaldehyde N-Triftosylhydrazone with Organoboronic Acids for the Synthesis of gem-Difluoroalkenes
Ma, Yu,Reddy, Bhoomireddy Rajendra Prasad,Bi, Xihe
supporting information, p. 9860 - 9863 (2019/12/24)
The synthesis of alkyl gem-difluoroalkenes remains a difficult task in organic synthesis. Here, we report a general and efficient approach for tackling this problem by gem-difluoroolefination of trifluoroacetaldehyde N-triftosylhydrazone with organoboronic acids. This protocol is operationally simple, free of transition metals, and suitable for a broad range of organoboronic acids. Moreover, the utility of the products was demonstrated by further conversion of the gem-difluorovinyl group.
Metal-Free Access to (E/Z)-α-Fluorovinyl Phosphorus Compounds from gem-Difluorostyrenes
Peng, Yingyuan,Zhang, Xiaofei,Qi, Xueyu,He, Qian,Zhang, Bin,Hao, Jian,Yang, Chunhao
, p. 1170 - 1177 (2019/01/16)
A facile and efficient method for the synthesis of (E/Z)-α-fluorovinyl phosphorus compounds from gem-difluorostyrenes with diphenylphosphine oxide/dialkyl phosphate and DBU at room temperature was developed. A series of 1-fluorovinyl phosphine oxides/phosphonates were obtained with moderate to excellent yields in these reactions. Additionally, most isomers (E/Z type) of the target compounds could be easily separated and purified by column chromatography.
