Copper-Catalyzed Regioselective Monodefluoroborylation of Polyfluoroalkenes en Route to Diverse Fluoroalkenes (original) (raw)
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Recent Advances in the Synthesis of Difluoromethylated Arenes
Synlett, 2014
The growing importance of fluorinated compounds in pharmaceuticals, agrochemicals, and materials has triggered the development of new methods for the introduction of fluorine into small molecules. Although it is a challenge to prepare fluorinated compounds, new developed reactions are addressing this challenge and facilitating the synthesis of difluoromethylated arenes. In this article, we highlight recently important developments in the synthesis of difluoromethylated arenes. 1 Introduction 2 Cross-Coupling with Copper 3 Cross-Coupling with Palladium 4 Cross-Coupling with Other Metals 5 C(sp 2)-H Activation 6 C(sp 3)-H Activation 7 Conclusion
Copper-Catalyzed ipso-Borylation of Fluoroarenes
ACS Catalysis, 2017
ipso-Borylation of fluoroarenes has been achieved using an air-stable copper complex as a catalyst. Mechanistic studies suggest that the reaction proceeds via an S RN 1 mechanism involving a single-electron-transfer (SET) process and not via the typical S N Ar mechanism. This method differs from the previously reported nickel/copper-cocatalyzed system in terms of scope of the substrate and has exhibited good scalability. Double and triple ipso-borylations of several di-and trifluoroarenes have been also achieved efficiently, enhancing the synthetic utility of this method.
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Advanced Synthesis & Catalysis, 2015
Ac opper-mediated halotrifluoromethylation of unactivated alkenesusing Umemotos reagent and copper(I) halide (CuX, X = Cl, Br, and I) was developed. TheC uX species (CuI, CuBr, and CuCl) were chosen as the source for bothc opper andh alides because of theirb enchtop stability,c ommercial availability,a nd relatively low cost. Simple exchange of the copper salt provided the desired simultaneous and regioselective incorporation of the halogen atom and of the CF 3 group to various alkenes. This protocol offers an efficienta nd practical route to various b-halotrifluoromethylateda lkanes.F urther modifications of the C À Br bond to C À B, C À Na nd C À Sb onds were performed. These derivatizations show the feasibility of late-stage modifications.
Jayaraman, A.; Lee, S.Org. Lett. 2019, 21(10), 3485-3489.
A variety of arylalkynoic acids reacted with 1,3-diiodo-5,5-dimethylhydantoin and HF·pyridine in the presence of AgOAc to provide the corresponding 1-fluoro-2,2-diiodovi-nylarenes in good yields and high regioselectivity. In addition, Pd-catalyzed cross-coupling reaction of 1-fluoro-2,2-diiodovi-nylarenes afforded diaryl coupling products in the Suzuki reaction and monoaryl coupling products with high stereo-selectivity in the Hiyama reaction. It was found that C−F-activated borylation of fluoroalkenes using Pd catalyst afforded the vinylboranes with good yields. M any biological and medicinal products, as well as important functional materials, contain the fluorine functionality. 1 Substitution of hydrogen with fluorine in organic materials can dramatically change the reactivity and the chemical, physical, and biological properties of the corresponding compounds. 2 As a consequence, fluorinated compounds have recently gained considerable attention in various fields, and the number of methodologies introducing the fluorine functionality into organic compounds has increased drastically over the last few decades. 3 Fluoroalkene, one of the numerous fluorine-containing compounds, is an important structural motif found in many bioactive compounds and is a useful building block. 4 A variety of synthetic methods for fluoroalkenes have been reported in the literature, and hydrofluorination of alkynes is one such straightforward method (Scheme 1a). 5 Sadighi first reported hydrofluorination of alkynes using Au catalyst to furnish fluoroalkenes in good yields. A number of Au-catalyzed hydrofluorination reactions of alkynes have been developed by several groups. In addition, it was reported that alkynes having a carbonyl group could be converted into the corresponding fluoroalkenes under metal-free or copper catalysis conditions (Scheme 1b). 6 Moreover, fluoroalkene derivatives 1,2-bromofluoro-and 1,2-fluoroiodoalkenes have received considerable attention as useful fluorinated building blocks because these vinyl bromides and iodides can be further transformed into versatile molecules via cross-coupling reactions (Scheme 1c). Jiang demonstrated that 1,2-bromofluoroalkenes could be synthesized by the reaction of terminal alkynes with NBS/AgF. 7 Synthesis of 1,2-fluoroiodoalkenes was accomplished by the fluoroiodination of alkynes employing HF-based reagents along with the iodine reagents such as I 2 , Tol-IF 2 , IF 5 , PhIO, and 1,3-diiodo-5,5-dimethylhydantoin (DIH). 8 In contrast, much less attention has been paid toward gem-dihalo-substituted fluoroalkenes, although in theory, they are highly likely to be employed as coupling partners in the cross-coupling reactions for the preparation of mono-and disubstituted fluoroalkenes. It has been reported that the preparation of gem-dibromo-and gem-dichlorofluoroalkenes from aldehydes requires a multistep process (Scheme 1d). 9 Therefore, simple and one-step synthetic methods are required.
The synthesis of arylboronic acids and aryl trifluoroborates in a one-pot sequence by Ir-catalyzed borylation of arenes is reported. To prepare the arylboronic acids, the Ir-catalyzed borylation is followed by oxidative cleavage of the boronic ester with NaIO 4. To prepare the aryltrifluoroborate, the Ir-catalyzed borylation is followed by displacement of pinacol by KHF 2. These two-step sequences give products that are more reactive toward subsequent chemistry than the initially formed pinacol boronates.
This report is concerned with an efficient, Cu I -mediated method for the radiosynthesis of [ 18 F]trifluoromethyl arenes, abundant motifs in small molecule drug candidates and potential radiotracers for positron emission tomography. Three 18 F-labelled radiotracer candidates were synthesised from [ 18 F]fluoride ions as proof of principle. The new protocol is widely applicable for the synthesis of novel radiotracers in high radiochemical yields.