Palladium‐Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide

Abstract

An efficient palladium‐catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high‐value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl‐containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.

Palladium‐Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand‐Assisted Halide Exchange

“…This result confirms that CO is released in our reaction. The need to release CO is consistent with previous reports showing that the formation of aroyl‐Pd‐X (X=halogen) complexes is highly favored over aryl‐Pd‐X complexes in the presence of CO [27a, 28, 31e] . Therefore, extrusion of CO from the reaction mixture is necessary to avoid CO re‐insertion and to drive the equilibrium towards the aryl‐Pd‐X complex.…”

“…This observation, paired with the absence of olefinic by-products and the fact that tert-butyl iodide hardly affords the desired product, iodobenzene (3 a), speaks against a mechanism involving oxidative addition into the aliphatic carbonÀiodine bond and b-hydride elimination to activate the reagent. [27,34] To test this hypothesis, we synthesized heavier alkyl iodide 2-(2-iodoethyl)naphthalene (10) and subjected it to our standard reaction conditions. The corresponding halide exchange product-alkyl chloride 11could be isolated in 95 % yield without any signs of olefinic by-products (Scheme 3 a).…”

Palladium‐Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide

“…We started our investigation by performing astoichiometric experiment between bromobenzene,Pd 2 (dba) 3 ,and Xantphos.A fter four hours at 80 8 8C, it was possible to isolate ac omplex which was confirmed to be the oxidative addition product 9 by X-ray and NMR analysis (Scheme 2a). [20,29,30] TheNMR resonances of the complex are in accordance with literature values for similar complexes. [29] Next, we turned our attention on the reaction of butyryl chloride and Pd 0 .P ioneering work on the oxidative addition of Pd 0 complexes into aliphatic acid chlorides was reported by Skrydstrup using P(t-Bu) 3 as ligand.…”

“…Theidentity of 7j could be further confirmed by single crystal X-ray analysis of the corresponding methyl ester. [24] One-Pot Synthesis of Carbonyl-Containing Products Acid chlorides exhibit high reactivity towards ag reat variety of nucleophiles.T aking advantage of this property,the chlorocarbonylation of aryl (pseudo)halides can be exploited to give access to ab road spectrum of carbonyl-containing products.The acyl chloride product can be used as aplatform for further in situ derivatization, thus enabling the one-pot synthesis of diverse carbonyl products starting from aryl (pseudo)halides (Table 5).…”

Palladium‐katalysierte decarbonylierende Iodierung von Carbonsäuren, ermöglicht durch Ligand‐unterstützten Halogenaustausch

“…Diese Beobachtung,g epaart mit der Abwesenheit von olefinischen Nebenprodukten und der Tatsache,dass tert-Butyliodid kaum das gewünschte Produkt, Iodbenzol (3a), liefert, spricht gegen einen Mechanismus,d er eine oxidative Addition in die aliphatische Kohlenstoff-Iod-Bindung und eine b-Hydrid-Eliminierung zur Aktivierung des Reagenzes beinhaltet. [27,34] Um diese Hypothese zu testen, synthetisierten wir das schwerere Alkyliodid 2-(2-Iodethyl)naphthalin (10)u nd unterzogen es unseren Standard-Reaktionsbedingungen. Das entsprechende Halogenid-Austauschprodukt -A lkylchlorid 11 -k onnte in 95 %A usbeute ohne Anzeichen von olefinischen Nebenprodukten isoliert werden (Schema 3a).…”