Copper-Catalyzed Trifluoromethylation of Terminal Alkenes through Allylic C–H Bond Activation

Xu, Jun; Fu, Yao; Luo, Dong‐Fen; Jiang, Yuan‐Ye; Xiao, Bin; Liu, Zhao‐Jing; Gong, Tian‐Jun; Liu, Lei

doi:10.1021/ja206330m

Cited by 358 publications

(111 citation statements)

References 65 publications

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“…[9,10] During the course of our studies, we observed 5, a side product resulting from chloride counterion transfer from CuCl to the olefin substrate subsequent to C-CF 3 bond formation (Figure 1, A). We hypothesized several possible intermediates (summarized as 6) leading to the formation of both 4 and 5.…”

Section: Abstract Trifluoromethylation; Fluorine; Iron; Catalysismentioning

confidence: 88%

Iron(II)‐Catalyzed Trifluoromethylation of Potassium Vinyltrifluoroborates

2012

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An iron(II)-catalyzed trifluoromethylation of potassium vinyltrifluoroborates has been developed. The reactions proceed under mild conditions and provide E/Z selectivities of > 95:5 for 2-aryl and -heteroarylvinyl substrates. Experimental observations suggest that the reaction does not proceed through a transmetallation of the RBF 3 K to the iron catalyst. Keywords trifluoromethylation; fluorine; iron; catalysisThe incorporation of fluorinated functional groups in pharmaceutical and agrochemical molecules has had a significant impact on the discovery and development of biologically active compounds. [1,2] Due to its metabolic stability, lipophilicity, and electron-withdrawing character, [3] use of the trifluoromethyl (CF 3 ) substituent has gained considerable attention in recent years. New methods for direct C-CF 3 bond-formation have had a prominent presence in current literature, highlighting the importance of this transformation. [4,5] Efforts in our lab have focused on the development of new fluorination [6] and trifluoromethylation [7] reactions through the use of transition metal catalysis and promotion. Herein, we report a facile method to access vinyl-CF 3 functional groups through an iron(II)-catalyzed trifluoromethylation of potassium vinyltrifluoroborates (1) using Togni's reagent 2 [8] (eq 1).Recently, we reported an oxidative trifluoromethylation of terminal olefins, providing rapid access to allyl-CF 3 containing products of type 4. [9,10] During the course of our studies, we observed 5, a side product resulting from chloride counterion transfer from CuCl to the olefin substrate subsequent to C-CF 3 bond formation (Figure 1, A). We hypothesized several possible intermediates (summarized as 6) leading to the formation of both 4 and 5. [*] Fax: (+1) 617-253-329 sbuchwal@mit.edu. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. After consideration of these possibilities, we surmised that regioisomeric products (i.e. vinyl-CF 3 containing molecules) might be accessed through a similar type of reactive intermediate. Toward this end, we sought to bias the presumed product-forming step through the use of a functionalized vinyl substrate such as a vinylboron reagent (Figure 1, B). Thus, trifluoromethylation of 7 would lead to formation of intermediate 6d. Loss of the boronbased functional group would result in the generation of the desired vinyl-CF 3 containing product. NIH Public AccessWe commenced our studies by examining the trifluoromethylation of styryl-BX n reagents with 2 using various metal catalysts. During our preliminary studies, we discovered that both copper(I) [11] and iron(II) chloride provided a satisfactory yield of product 3a (Table 1, entries 1-4). Due to the low cost and cleaner reaction profile, we continued our studies using catalytic FeCl 2 by examining various vinylboron reagents (Table 1, entries 2-4). Interestingly, the E/Z product ratio varied significantly depending on the identity of styryl-BX n r...

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Section: Abstract Trifluoromethylation; Fluorine; Iron; Catalysismentioning

confidence: 88%

Iron(II)‐Catalyzed Trifluoromethylation of Potassium Vinyltrifluoroborates

2012

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“…In 2011, Parsons et al, 84 Xu et al, 85 and Wang et al 86 reported the trifluoromethylation of unactivated olefins with a copper(I) salt and either Umemoto or Togni reagent ( Figure 39). Although these reactions provide accesses to compounds bearing CF 3 at allylic positions, these transformations are restricted to monosubstituted terminal olefins.…”

Section: Synthesis Of Alkenyl and Alkyl Trifluoridesmentioning

confidence: 99%

“…Different mechanisms were proposed for these methods, including radical addition of CF 3 to alkenes (Parsons et al) 84 and migration insertion of Cu III -CF 3 to double bond (Xu et al). 85 Allylsilanes are also good substrates for copper-catalyzed trifluoromethylation to give trifluoromethylated products. Shimizu et al found that different types of allylsilanes undergo facile trifluoromethylation to afford either gem-disubstituted terminal olefins or vinylsilanes bearing a CF 3 on the allylic position ( Figure 40).…”

Section: Synthesis Of Alkenyl and Alkyl Trifluoridesmentioning

confidence: 99%

Recent advances in green fluorine chemistry

Zeng¹,

Hu²

2015

ROC

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“…9 Using these methods, a new Csp 3 -CF 3 bond could be constructed under the practical and mild reaction conditions. Based on theoretical calculations, Liu and co-workers proposed that the reaction may proceed through a Heck-like four-membered ring transition state.…”

Section: Introductionmentioning

confidence: 99%

Umemoto's Reagent

Li¹

2012

Synlett

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This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and preparation of the reagent in current research spotlight Umemoto's Reagent Compiled by Huiqin LiHuiqin Li was born in Henan Province, P. R. of China, in 1988. She studied chemistry at the Northeast Normal University, Changchun, where she obtained her B.Sc. degree in 2011. She is currently pursuing her M.Sc. under the supervision of Prof. Xihe Bi. Her current research project is focused on heterocycle synthesis mediated by fluoro-containing reagents.

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Copper-Catalyzed Trifluoromethylation of Terminal Alkenes through Allylic C–H Bond Activation

Cited by 358 publications

References 65 publications

Iron(II)‐Catalyzed Trifluoromethylation of Potassium Vinyltrifluoroborates

Iron(II)‐Catalyzed Trifluoromethylation of Potassium Vinyltrifluoroborates

Recent advances in green fluorine chemistry

Umemoto's Reagent

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