Ag(<scp>i</scp>)-Mediated hydrogen isotope exchange of mono-fluorinated (hetero)arenes

Hu, Guang-Qi; Li, En-Ci; Zhang, Hong-Hai; Huang, Wei

doi:10.1039/d0ob01273d

Cited by 20 publications

(11 citation statements)

References 74 publications

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“…Simple silver salts have been shown to effect H/D exchange in pentafluorobenzene (or heptafluorotoluene) with D 2 O + AgOPiv (Piv = pivalate). − H/D exchange with D 2 O in the position ortho to the fluorine of a fluoroarene (or a metal complex of fluoroarene) was also reported, employing Ag 2 CO 3 (or Ag 2 O) and a bulky phosphine (Scheme , eq ). − Similar studies including DFT calculations have been reported with AgOC(O)Ad + PPh 3 (Ad = adamantyl) …”

Section: Introductionsupporting

confidence: 66%

Direct Evidence for Competitive C–H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C–H Functionalization

et al. 2022

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Increasing evidence indicates that silver salts can play a role in the C−H activation step of palladium-catalyzed C−H functionalization. Here we isolate a silver(I) complex by C−H bond activation and demonstrate its catalytic competence for C−H functionalization. We demonstrate how silver carbonate, a common but highly insoluble additive, reacts with pentafluorobenzene in the presence of a bulky phosphine, XPhos, to form the C−H bond activation product Ag(C 6 F 5 )(XPhos). By isolating and fully characterizing this complex and the related carbonate and iodide complexes, [Ag(XPhos)] 2 (μ-κ 2 ,κ 2 -CO 3 )a n d[ A g I -(XPhos)] 2 , we show how well-defined Ag(I) complexes can operate in conjunction with palladium complexes to achieve C−H functionalization even at ambient temperature. Reactions are tested against the standard cross-coupling of C 6 F 5 H with 4-iodotoluene, catalyzed by palladium acetate at 60 °C in the presence of silver carbonate and Xphos. Key observations are that (a) PdI(C 6 H 5 )(XPhos) reacts stoichiometrically with Ag(C 6 F 5 )(XPhos) to form Ph−C 6 F 5 instantly at room temperature; (b) catalytic cross coupling can be achieved using 5% Ag(C 6 F 5 )(XPhos) as the sole silver source; and (c) palladium acetate (typical precatalyst) can be replaced for catalytic cross coupling by the expected oxidative addition compound PdI(C 6 H 5 )(XPhos). These investigations lead to a catalytic cycle in which Ag(I) plays the C−H bond activation role and palladium plays the coupling role. Moreover, we show how the phosphine can be exchanged between silver complexes, ensuring that it is recycled even though silver carbonate is consumed during catalytic cross-coupling.

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Section: Introductionsupporting

confidence: 66%

Direct Evidence for Competitive C–H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C–H Functionalization

et al. 2022

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“…While the above-described silver and acid/base-catalyzed deuteration methodologies label electron-rich positions preferentially, a silver/phosphine ligand-catalyzed system similar to the one described above was recently applied to the ortho -selective deuteration of mono fluoroarenes by the same group (Scheme a). , Here, the selectivity for the ortho position presumably stems from its higher acidity, thus being in line with electronically controlled activation. Remarkably, the presence of pyridine directing groups does not affect the outcome of the silver-catalyzed reaction, rendering this methodology complementary to directed HIE.…”

Section: Hydrogen Isotope Exchangementioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017−2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

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“…In the frequent situation that the base is silver carbonate or another silver salt, this mechanistic hypothesis has been unraveling. Several publications, notably from the Sanford, Hartwig, and Larrosa groups, have recently demonstrated that silver(I) complexes are active in C–H activation even in the absence of palladium. − Evidence comes from the detection of silver aryl complexes, H/D exchange reactions, and study of the kinetics of cross-coupling; a scheme summarizing the evidence may be found in ref . The evidence for silver participation has also been reviewed. − We recently reported that the reaction of Ag 2 CO 3 with XPhos in the presence of pentafluorobenzene yields Ag(C 6 F 5 )(XPhos) and showed that this is a mononuclear complex that is linear at silver.…”

Section: Introductionmentioning

confidence: 99%

Opening a Pandora’s Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag₂CO₃/Pd(OAc)₂/PPh₃ System

Platt,

Aguiar,

Athavan

et al. 2023

Organometallics

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Direct C–H functionalization reactions have opened new avenues in catalysis, removing the need for prefunctionalization of at least one of the substrates. Although C–H functionalization catalyzed by palladium complexes in the presence of a base is generally considered to proceed by the CMD/AMLA-6 mechanism, recent research has shown that silver(I) salts, frequently used as bases, can function as C–H bond activators instead of (or in addition to) palladium(II). In this study, we examine the coupling of pentafluorobenzene 1 to 4-iodotoluene 2a (and its analogues) to form 4-(pentafluorophenyl)toluene 3a catalyzed by palladium(II) acetate with the commonplace PPh 3 ligand, silver carbonate as base, and DMF as solvent. By studying the reaction of 1 with Ag 2 CO 3 /PPh 3 and with isolated silver (triphenylphosphine) carbonate complexes, we show the formation of C–H activation products containing the Ag(C 6 F 5 )(PPh 3 ) n unit. However, analysis is complicated by the lability of the Ag–PPh 3 bond and the presence of multiple species in the solution. The speciation of palladium(II) is investigated by high-resolution-MAS NMR (chosen for its suitability for suspensions) with a substoichiometric catalyst, demonstrating the formation of an equilibrium mixture of Pd(Ar)(κ 1 -OAc)(PPh 3 ) 2 and [Pd(Ar)(μ-OAc)(PPh 3 )] 2 as resting states (Ar = Ph, 4-tolyl). These two complexes react stoichiometrically with 1 to form coupling products. The catalytic reaction kinetics is investigated by in situ IR spectroscopy revealing a two-term rate law and dependence on [Pd tot /nPPh 3 ] 0.5 consistent with the dissociation of an off-cycle palladium dimer. The first term is independent of [ 1 ], whereas the second term is first order in [ 1 ]. The observed rates are very similar with Pd(PPh 3 ) 4 , Pd(Ph)(κ 1 -OAc)(PPh 3 ) 2 , and [Pd(Ph)(μ-OAc)(PPh 3 )] 2 catalysts. The kinetic isotope effect varied significantly according to conditions. The multiple speciation of both Ag I and Pd II acts as a warning against specifying the catalytic cycles in detail. Moreover, the rapid dynamic interconversion of Ag I species creates a level of complexity that has not been appreciated previously.

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Ag(i)-Mediated hydrogen isotope exchange of mono-fluorinated (hetero)arenes

Abstract: An efficient approach to install deuterium into mono-fluorinated (hetero)arenes by Ag2CO3/Sphos mediated HIE protocol with D2O as deuterium source has been disclosed. This method showed specific site-selectivity of deuteration at...

Cited by 20 publications

References 74 publications

Direct Evidence for Competitive C–H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C–H Functionalization

Direct Evidence for Competitive C–H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C–H Functionalization

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Opening a Pandora’s Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag₂CO₃/Pd(OAc)₂/PPh₃ System

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Ag(i)-Mediated hydrogen isotope exchange of mono-fluorinated (hetero)arenes

Abstract: An efficient approach to install deuterium into mono-fluorinated (hetero)arenes by Ag2CO3/Sphos mediated HIE protocol with D2O as deuterium source has been disclosed. This method showed specific site-selectivity of deuteration at...

Cited by 20 publications

References 74 publications

Direct Evidence for Competitive C–H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C–H Functionalization

Direct Evidence for Competitive C–H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C–H Functionalization

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Opening a Pandora’s Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag2CO3/Pd(OAc)2/PPh3 System

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Opening a Pandora’s Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag₂CO₃/Pd(OAc)₂/PPh₃ System