Palladium‐Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides

Abstract

While acid fluorides can readily be made from widely available or biomass‐feedstock‐derived carboxylic acids, their use as functional groups in metal‐catalyzed cross‐coupling reactions is rare. This report presents the first demonstration of Pd‐catalyzed decarbonylative functionalization of acid fluorides to yield trifluoromethyl arenes (ArCF3). The strategy relies on a Pd/Xantphos catalytic system and the supply of fluoride for transmetalation through intramolecular redistribution to the the Pd center. This strategy eliminated the need for exogenous and detrimental fluoride additives and allows Xantphos to be used in catalytic trifluoromethylations for the first time. Our experimental and computational mechanistic data support a sequence in which transmetalation by R3SiCF3 occurs prior to decarbonylation.

Orthogonal Nanoparticle Catalysis with Organogermanes

“…[21][22][23][24] We envisioned that adetailed investigation of the fundamental aspects of the coupling process involving organogermanium compounds might likely offer inspiration. [12,25] Indeed, while the organogermane remained untouched ( Figure 3), our comparative studies showed that organoboron reagents react with the same Pd II ÀFc omplex within seconds,a nd organosilane and organotin reagents within an hour at room temperature (see the Supporting Information, Table S1). In particular,P d II ÀFc omplexes are usually privileged intermediates that typically undergo direct transmetalation with the established cross-coupling partners ArSiR 3 ,A rSnR 3 ,o rA rB(OH) 2 without the need for additives.…”

“…[16] To our delight, when we performed the coupling of triethyl(pentafluorophenyl)germane with aryl iodides,w e obtained near-quantitative yields (27,28). Moreover,g ood yields were obtained also for heterocyclic variants,that is,the 2-and 3-germylated thiophene (24)(25)(26)o rf uran (19,20) reagents.E ven the most challenging substrates,2 -pyridyl germanes,p roved to be robust and stable and allowed for efficient cross-couplings (21-23, 39, 40). Thec oupling of 2-pyridylboronic acids has been al ong-standing challenge because of their inherent instability.B urke and co-workers recently developed as olution through the use of MIDA …”

“…With these successful conditions in hand, we subsequently set out to couple those moieties that are known to be tremendously challenging in the widely employed Suzuki cross-coupling,that is,polyfluorinated arenes (27 and 28)and the medicinally and pharmaceutically relevant heterocycles thiophene,f uran, and pyridine (19)(20)(21)(22)(23)(24)(25)(26). Thec ase of pentafluorophenylboronic acid has long been ac hallenge because of its propensity to undergo protodeboronation, [13] typically requiring "designer" conditions.…”

Palladium‐Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature

“…[14] They are ubiquitous in important classes of organic molecules,i ncluding natural products,p harmaceuticals,a nd materials,a nd thus decarbonylative cross coupling offers an opportunity for expedient derivatization of such compounds that the known methods cannot provide. [19] Our reaction constitutes ahighly unusual example of decarbonylative cross coupling of ac arboxylic acid derivative that proceeds at rapid rates (as little as 5minutes to full conversion) at room temperature. Herein, we present an ew strategy for aromatic difluoromethylation through direct decarbonylative cross coupling of aromatic acid chlorides,o btained in situ from carboxylic acids,a tr oom temperature.A lthough various transitionmetal-catalyzed decarbonylative transformations of aromatic acids have been reported, these transformations usually require high temperatures and long reaction times,w hich limits substrate scope,e specially for late-stage applications.…”

Säurefluoride in der Übergangsmetallkatalyse: Balance von Stabilität und Reaktivität

“…Es wurde gefunden, dass Tr is(4-methoxyphenyl)phosphan (L1)und Tr icyclohexylphosphan (L2)die besten Liganden für dieses Verfahren sind. [11] Tatsächlich hatte ein früherer Bericht hervorgehoben, dass fürd ie Tr ifluormethylierung von oxidativen Additionskomplexen der Xantphos-Ligand notwendig st, damit eine reduktive Eliminierung erfolgt, ganz entscheidend für den Schritt der Tr ansmetallierung mit dem CF 3 -Anion ist aber insbesondere die Bildung des Pd II -F-Intermediats. (1)] ist die Suzuki-Miyaura-Reaktion allgemeiner durchführbar,u nd die Bildung unsymmetrischer Aryl-, Heteroaryl-, Alkyl-und Alkenylketone 3 erfolgte in mäßigen bis hohen Ausbeuten.…”