Copper‐Catalyzed Trifluoromethylation of Unactivated Olefins

Parsons, Andrew T.; Buchwald, Stephen L.

doi:10.1002/ange.201104053

Cited by 157 publications

(83 citation statements)

References 58 publications

(27 reference statements)

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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: 85%

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: 85%

Iron(II)‐Catalyzed Trifluoromethylation of Potassium Vinyltrifluoroborates

2012

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“…[21] Belichtung des Katalysators 5 mit einer 26-W-Fluoreszenzlichtquelle führt zum entsprechenden angeregten Iridiumkomplex, der einen SET auf CF 3 [22] Der Bartonsche Thiohydroxamsäuretrifluormethylester wurde als einfach herstellbare CF 3 -Radikalvorstufe vorgeschlagen, [23] und Trifluormethansulfonylchlorid erwies sich ebenfalls als wertvolle Quelle des CF 3 Buchwald et al [27] und Wang et al [28] berichteten unabhängig voneinander, dass das kommerziell erhältliche TogniReagens 14 [29] als CF 3 -Radikalquelle genutzt werden kann (Schema 4). Nichtaktivierte Alkene 13 reagierten mit 14 in Gegenwart eines Kupfer(I)-Katalysators (10-15 Mol-%) in einer allylischen Trifluormethylierung zu 15.…”

Section: Radikalische Trifluormethylierung Von Alkenenunclassified

Die “Renaissance” der radikalischen Trifluormethylierung

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2012

Angewandte Chemie

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Dieser Kurzaufsatz stellt jüngste Entwicklungen auf dem Gebiet radikalischer Trifluormethylierungen vor. Die Trifluormethylgruppe zählt zu den privilegierten Struktureinheiten in der Medizinalchemie. Viele Wirkstoffe und Wirkstoffkandidaten enthalten die Trifluormethylgruppe, und auch in Agrochemikalien findet sich oft eine CF3‐Einheit. Der vorliegende Kurzaufsatz befasst sich mit radikalischen Trifluormethylierungen von Alkenen und Arenen, wobei besonders auf die jüngsten Entwicklungen eingegangen wird; wichtige frühere Arbeiten werden jedoch ebenfalls diskutiert.

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“…[7] In contrast, it is apparent that trifluoromethylation of simple alkenes is still developing. [8][9][10][11] Recently, Parsons and Buchwald,…”

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confidence: 96%