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

Abstract

Wirb erichten über eine effiziente und breit anwendbare Palladium-katalysierte Iodierung günstiger und leichtverfügbarer Aryl-und Vinylcarbonsäuren durch In-situ-Aktivierung zum Säurechlorid und Bildung eines Phosphoniumsalzes.D ie Verwendung von 1-Iodbutan als Iodidquelle in Kombination mit einer Base und einem Desoxychlorierungsreagenz erçffnet den Zugang zu einer Vielzahl von Aryl-und Vinyliodiden unter Pd/Xantphos-Katalyse,e inschließlich komplexer arzneimittelähnlicher Strukturen. Stçchiometrische Experimente und kinetische Analysen legen einen einzigartigen Mechanismus nahe,w elcher die reduktive C-P-Eliminierung zur Bildung des Xantphos-Phosphoniumchlorids beinhaltet, welches anschließend einen ungewçhnlichen Halogenaustauschdurch nukleophile Substitution initiiert. EinleitungOrganische Halogenide gehçren zu den am weitesten verbreiteten funktionellen Gruppen in der organischen Chemie und reichen in ihrer Anwendung von Naturstoffen, [1] Pharmazeutika [2] und Agrochemikalien [3] bis hin zu funktionellen Materialien [4] und molekularer Erkennung. [5] Darüber hinaus sind Halogenide wichtige Bausteine in der organischen Chemie und dienen als synthetische Ansatzpunkte,z.B.durch Aktivierung der Kohlenstoff-Halogen-Bindung mit Übergangsmetallen, [6] Metall-Halogen-Austausch [7] oder nukleophile Substitution. [8] Zahlreiche Methoden zur Bildung von Ruthenium-, [9] Rhodium-, [10] Nickel-, [11] Kupfer-katalysierten [12] und übergangsmetallfreien [13] C(sp 2 )-Halogen-Bindungen wurden bisher beschrieben. [6] In den letzten Jahrzehnten

Palladium-Catalyzed Decarbonylative Nucleophilic Halogenation of Acyl Fluorides and Chlorides: Synthesis of Aryl Halides via Reductive Elimination of the C–X (X = I, Br, and Cl) Bond and Mechanistic Implications

“…In contrast, the optimization of the decarbonylative iodination reaction conditions for 1-naththoyl chloride ( 1a′ ), which are cheaper building blocks in industrial organic synthesis, is briefly detailed in Table . Consistent with the findings reported by Morandi et al, LiI was found to be unsuitable for this conversion. Examination of the reaction progress revealed that the reaction ceased only 15 min after its initiation.…”

“…Furthermore, under standard conditions, 2ab was consumed, leading to the formation of 2b in 34% yield (Figure b). Consistent with prior findings, these experimental outcomes suggest a phosphonium-mediated reversible reductive elimination/oxidative addition of the C(aryl)–P bond. As illustrated in Figure c, oxidative addition of 2ab to (Xantphos)Pd 0 gives rise to Int-I , followed by reductive elimination guided by the electron-rich p -anisyl group and phosphorus bond formation, affording the formation of phosphonium salt-ligated Pd complex Int-II .…”

“…Three Pd intermediates were identified: (Xantphos)Pd II (COPh)I ( 6 ) at −0.3 ppm, (Xantphos) 2 Pd 0 at 3.5 and 5.2 ppm (two broad multiplets), and (Xantphos)Pd II (Ph)I ( 7 ) at 10.0 ppm (see Figure S5 in the Supporting Inormation for details). Signals for each compound were either assigned by preparing authentic samples of each intermediate (see Section 5.2 in the Supporting Inormation for details) or were consistent with previous reports. , Complex 6 appears to be a plausible resting state, while the others were observed in the early stages of the reaction. Next, to determine if complexes 6 and 7 were indeed part of the catalytic cycle, they were synthesized according to their reported methods and employed as catalysts for the iodination of acyl fluoride 1b (Table ).…”

“…This suggests that under conditions without the addition of an external Xantphos ligand, the CO eliminated from complex 6 ligates to the palladium center, contributing to the stabilization of the catalyst. It is considered that the added Xantphos and carbonyl ligands stabilize Pd 0 species generated after reductive elimination of Ar–I, rendering the catalytic cycle more efficient. ,, The unmentioned Pd complex, (Xantphos)PdI 2 at 3.8 ppm was found to be completely inactive (see Supporting Inormation 5.4 for details).…”

“…Building upon the pioneering work of Schoenebeck and Keaveney in 2018, wherein Pd-catalyzed trifluoromethylation of acyl fluorides was achieved, subsequent investigations by various groups, , including our own research team, have unveiled diverse decarbonylative transformations of acyl fluoride, underscoring its distinctive reactivity. In the pursuit of methods for synthesizing organic iodides from carboxylic acid derivatives, the Pd-catalyzed decarbonylative iodination of acyl chlorides by Morandi and Arndtsen stands out, earning acclaim for their significant breakthrough in Ar–I bond formation through reductive elimination from Pd(II) species. The Xantphos ligand with its large bite angle (β n = 111°) and steric bulk, played a pivotal dual role in accelerating reductive elimination of the carbon–iodine bond .…”