Iron(II)‐Catalyzed Trifluoromethylation of Potassium Vinyltrifluoroborates

Abstract

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...

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

“…Die meisten N-Heteroarene und elektronenreiche Arene reagieren mit dem Togni-Reagens zu mehrfach trifluormethylierten Produkten. [284] Auch die silbervermittelte Trifluormethylierung nicht aktivierter Arene und Heteroarene mit TMSCF 3 soll über einen Radikalmechanismus zu trifluormethylierten Produkten verlaufen (Schema 61). [278] [282] Die von Baran und MacMillan entwickelten Methoden ermçglichen die effiziente direkte Synthese strukturell komplexer Trifluormethylarene, was vorher nicht mçglich war.…”

Photokatalyse mit sichtbarem Licht: Welche Bedeutung hat sie für die organische Synthese?

“…[272] In ähnlicher Weise sind auch andere Cu-katalysierte Methoden zum Aufbau gewünschter C(sp 2 )-CF 3 -Bindungen ausgehend von Alkenylboronsäuren 268 und Togni-Reagenz 271 bekannt, was von Shen und Mitarbeitern entwickelt wurde (Schema 75 b, links Mitte). [275] In einer photoredoxkatalysierten Va riante mit sichtbarem Licht, entwickelt von Cho und Mitarbeitern, wurde der ATRA-Prozess und die anschließende Dehalogenierung erfolgreich mit CF 3 Iu nd DBUk ombiniert (Schema 75, rechts). [274] Buchwald und Mitarbeiter beschrieben ein vielversprechendes Protokoll fürd ie Tr ifluormethylierung von Kaliumvinyltrifluorborat 270,d as in guten Ausbeuten und exzellenten E/Z-Selektivitäten unter Verwendung eines Eisen(II)-Katalysators und 271 als CF 3 -Quelle verläuft (Schema 75 d, links unten).…”

Recent advances in green fluorine chemistry

“…88 After a quick screening, the authors found that the ratio of E/Z isomers was dependent on the rate of elimination of the boron-based leaving group; thus, the poor leaving ability of BF 3 leads to the highest E/Z product ratio. Although the reaction conditions are mild, this method has some limitations, as electron-deficient and trisubstituted vinyl-BF 3 K salts furnish only trace amounts of products.…”