Photoinitiated oxidative addition of CF3I to gold(I) and facile aryl-CF3 reductive elimination.

Herein we report the mechanism of oxidative addition of CF3I to Au(I), and remarkably fast Caryl-CF3 bond reductive elimination from Au(III) cations. CF3I undergoes a fast, formal oxidative addition to R3PAuR' (R = Cy, R' = 3,5-F2-C6H4, 4-F-C6H4, C6H5, 4-Me-C6H4, 4-MeO-C6H4, Me; R = Ph, R' = 4-F-C6H4, 4-Me-C6H4). When R' = aryl, complexes of the type R3PAu(aryl)(CF3)I can be isolated and characterized. Mechanistic studies suggest that near-ultraviolet light (λmax = 313 nm) photoinitiates a radical chain reaction by exciting CF3I. Complexes supported by PPh3 undergo reversible phosphine dissociation at 110 °C to generate a three-coordinate intermediate that undergoes slow reductive elimination. These processes are quantitative and heavily favor Caryl-I reductive elimination over Caryl-CF3 reductive elimination. Silver-mediated halide abstraction from all complexes of the type R3PAu(aryl)(CF3)I results in quantitative formation of Ar-CF3 in less than 1 min at temperatures as low as -10 °C.

Introduction

Reports of organogold complexes undergoing redox processes are typically limited to slow oxidative additions and reductive eliminations.[1,2] However, organogold complexes are not necessarily unreactive; we recently showed that diaryl Au(III) complexes undergo remarkably fast aryl–aryl reductive elimination at temperatures as low as −50 °C.[3] These recent findings from our group, as well those established by Vicente,[4] Hashmi,[5] and Lloyd-Jones,[6] suggest that the barrier for challenging reductive eliminations might be substantially diminished at Au(III). Caryl–CF3 bond reductive elimination is typically a slow process requiring elevated temperatures and long reaction times, due to ground state stabilization afforded by exceptionally strong bonding between transition metals and CF3 ligands.[7] For instance, (dppbz)Pd(2-Me-C6H4)(CF3) (dppbz = 1,2-bis(diphenylphosphino)benzene) is stable at 130 °C for 3 days,[8] while (dppp)Pd(Ph)(CF3) (dppp = 1,3-diphenylphosphinopropane) and (dppe)Pd(Ph)(CF3) (dppe = 1,2-diphenylphosphinoethane) yield only 10% PhCF3 after 3 days at 145 °C.[9] Reductive eliminations at temperatures between 50 and 80 °C can be achieved at Pd(II) by employing bulky ligands, such as Xantphos[10] and Brettphos.[11] Notably, while aryl-CF3 reductive eliminations from Pd(IV) often require similarly high temperatures,[12a] Sanford has shown that they can occur at temperatures as low as 23 °C over 1 h.[12b] Despite advances in catalytic trifluoromethylation, Caryl–CF3 reductive elimination still remains a challenging step. Given the importance of trifluoromethylated arenes in pharmaceuticals and agrochemicals,[13] we were prompted to investigate potentially low-barrier Caryl–CF3 bond reductive elimination at Au(III).

To access complexes of the type R3PAu(aryl)(CF3)I, we were drawn to Puddephatt’s report of the oxidative addition of CF3I to Me3PAuMe to afford cis/trans mixtures of Me3PAuMe2(CF3) and Me3PAuI.[14] In one case, Me3PAu(Me)(CF3)I was obtained exclusively, but its preparation could not be reproduced by the authors. Because reaction times varied from 5 min to 1 day, and rates dramatically slowed in the presence of galvinoxyl, the authors concluded that a free-radical chain mechanism was operative, with •CF3 as the propagating species.

Results and Discussion

Prior investigations by our group revealed that oxidation of Ph3PAu(4-F-C6H4) rapidly generates 4,4′-difluorobiphenyl through a mechanism involving aryl group transfer.[3] However, the use of the bulkier PCy3 prevents transfer of the arene ligand, instead resulting in clean, rapid oxidation of Cy3PAu(4-F-C6H4) (1a) to the isolable Au(III) complex cis-(Cy3P)Au(4-F-C6H4)Cl2 (2) (eq 1).[15] Therefore, we began our investigations of Au(I) oxidation by CF3I using 1a, with the fluorinated arene ligand also providing a convenient 19F NMR handle. Treatment of 1a in CD2Cl2 with CF3I (25 equiv) afforded the product of formal CF3I oxidative addition 3a in 1 h in good yield (eq 2 and Table 1). Both the CF3 and PCy3 ligands (doublet at δ = −24.5 and quartet at δ = 25.6 in the 19F and 31P NMR spectra, respectively) provide diagnostic NMR signals (Table 2). The substantial coupling (3JP–F = 63 Hz) between fluorine and phosphorus are characteristic of a trans relationship between the CF3 and phosphine ligands.[14] X-ray analysis of crystals of 3a confirmed this stereochemical relationship around the square planar Au(III) (Figure 1A); other than the homoleptic anion [Au(CF3)4]−,[16] complex 3a contains a rare example of a crystallographically characterized Au(III)–CF3 bond. Complex 3a is not only stable to air and water but can be purified by column chromatography as well.

Table 1

Photoinitiated Oxidative Addition of CF3I to Electronically Diverse Au(I) Aryl Complexes 1a–1f, 11a, and 11b

Au(I) reactant	PR3	Ar	product	yield (%)
1a	PCy3	4-F-C6H4	3a	64
1b	PCy3	3,5-F2-C6H3	3b	44
1c	PCy3	C6H5	3c	59
1d	PCy3	4-Me-C6H4	3d	38
1e	PCy3	4-MeO-C6H4	3e	44
1f	PCy3	2-Me-C6H4	−	NR
11a	PPh3	4-F-C6H4	12a	71
11b	PPh3	4-Me-C6H4	12b	63

Table 2

31P{1H} and 19F NMR Data for Complexes 3a–3e, 12a, and 12b

complex	PR3	Ar	δ 31P{1H} (ppm)	δ 19F (ppm)
3a	PCy3	4-F-C6H4	25.6 (q, 3JP–F = 63 Hz)	–24.5 (d, 3JP–F = 63 Hz)
3b	PCy3	3,5-F2-C6H3	26.1 (q, 3JP–F = 63 Hz)	–22.0 (d, 3JP–F = 64 Hz)
3c	PCy3	C6H5	25.5 (q, 3JP–F = 62 Hz)	–22.7 (d, 3JP–F = 62 Hz)
3d	PCy3	4-Me-C6H4	25.5 (q, 3JP–F = 62 Hz)	–23.6 (d, 3JP–F = 62 Hz)
3e	PCy3	4-MeO-C6H4	23.3 (q, 3JP–F = 63 Hz)	–20.6 (d, 3JP–F = 64 Hz)
12a	PPh3	4-F-C6H4	20.0 (q, 3JP–F = 68 Hz)	–21.0 (d, 3JP–F = 68 Hz)
12b	PPh3	4-Me-C6H4	20.4 (q, 3JP–F = 67 Hz)	–21.3 (d, 3JP–F = 67 Hz)

Figure 1

(A–F) Thermal ellipsoid representations of 3a–3d, 12a, and 12b at the 50% probability level. Hydrogens have been omitted for clarity. Atoms are color-coded: gray (carbon), yellow (fluorine), gold (gold), purple (iodine), orange (phosphorus). See Supporting Information (SI) for bond lengths and angles.

Mechanism of Oxidative Addition of CF3I

The reaction of 1a and CF3I represents a rare oxidation of Au(I) to Au(III) that directly installs potentially reactive Au(III)–carbon bonds.[1] During our attempts to monitor the oxidative addition by 19F NMR, we found that no reaction occurred when the reaction mixture was placed inside the dark NMR spectrometer. However, when the reaction mixture was exposed to ambient fluorescent light for 5 min, the formation of 3a was detected (∼20%). Given the reliance of numerous methods on CF3I as a trifluoromethyl source,[17] we investigated its photochemical reactivity. Actinometry experiments were carried out to determine the overall quantum yield, using the Norrish II fragmentation of valerophenone as a standard.[18] The oxidative addition of CF3I to 1a was complete after 20 s of irradiation by a Hg vapor lamp (2 mM aq. K2CrO4 optical filter; transmittance λmax = 313 nm), while the fragmentation of valerophenone (Φ = 1) took place over 24 h under identical conditions. This rate difference, in addition to the ability of ambient light to bring the reaction to full conversion over variable reaction times (between 15 min and 1 h), supports a radical chain reaction as the mechanism of Au(I) oxidation by CF3I.

The reaction of excess CF3I and 1a is also fast in THF, but the conversion is never greater than 65% (52% yield of 3a), even when irradiated by a Hg vapor lamp for 1 h (vida infra). Notably, an excess of fluoroform (HCF3) is generated in THF, regardless of the light source (only DCF3 is formed when THF-d8 is used). GC-MS analysis of reaction mixtures reveals several products of THF oxidation, likely formed by H• abstraction by •CF3.

Several control experiments, using HCF3 production relative to a standard as a probe to detect •CF3 generation, support the involvement of Au(I) during the initiation of the chain reaction. The UV absorption of CF3I is centered at 270 nm but tails beyond 350 nm.[19] When irradiated at 313 nm, CF3I undergoes fast, reversible C–I bond homolysis. However, in the absence of , only negligible amounts of HCF3 are observed when THF solutions of CF3I are irradiated for 30 min, indicating that carbon/iodine radical recombination is substantially faster than H• abstraction from THF. Similarly insignificant quantities of HCF3 are observed when 20 equiv (relative to CF3I) of the H• donors 1,4-cyclohexadiene, 9,10-dihydroanthracene, or triphenylmethane are added (Figure 2A). Additionally, Cy3PAu(2-(CH2CH=CH2)C6H4) (4), containing a pendent olefin to either capture a putative Au(II) intermediate and/or •CF3, is fully consumed upon irradiation in the presence of excess CF3I (Figure 2B). This oxidation affords multiple Au(III) products of indiscriminate •CF3 addition to the terminal olefin and gold atom (and HCF3 when THF is used as solvent) (see SI). Because 2-allylbromobenzene (5) does not react with CF3I when irradiated under similar conditions (no HCF3 is observed after 5 min, and less than 2% after 30 min), we conclude that the Au(I) aryl complex is necessary for chain initiation. These results are also consistent with an initiation mechanism involving [CF3I]•–, which generates iodide and •CF3 following C–I bond homolysis.

Figure 2

Control experiments to assess involvement of Au(I) in the initiation of the radical chain mechanism. (A) Irradiation of CF3I solutions containing H• donors to detect CF3H in the absence of gold. (B) Radical trapping using an olefin with and without a pendant gold center.

We envisioned two possible initiation mechanisms for generating •CF3 as a propagating species from [CF3I]•– in a chain reaction: (1) initial photoexcitation of 6 followed by electron transfer to CF3I, or (2) initial photoexcitation of CF3I followed by electron transfer from 6 (Scheme 1).

Scheme 1

Possible Initiation Mechanisms Involving Photoexcitation of Either Au(I) Complex 6 (Mechanism 1) or CF3I (Mechanism 2)

Au(I) aryl complexes are well-known chromophores, and their photophysical properties have been investigated previously.[20] While 1a absorbs weakly above 310 nm (the cutoff for many laboratory fluorescent lamps[19]), excitation at 320 nm (ε = 37 M–1 cm–1) results in a weak, broad luminescence from 340 to 460 nm, classified as fluorescence based on the lifetime of excited species 1a* (<10 ns, quantum yield of fluorescence = 0.03).[21] Despite the short lifetime of 1a*, CF3I effectively quenches its fluorescence (Stern–Volmer quenching constant KSV = 30 M–1, Figure 3). Although this energy transfer could conceivably generate •CF3 and initiate a chain reaction (mechanism 1, Scheme 1), when CF3I is removed from fluorimetry samples under vacuum, fluorescence is restored to the same intensity prior to introduction of the gas, indicating that consumption of Au(I) has not occurred.

Figure 3

Stern–Volmer plots of fluorescence quenching of 1a by different concentrations of CF3I (blue boxes) and Au(III) complex 3a (blue triangles) in CH2Cl2. Concentrations of Au(III) are in mol/L and CF3I concentrations are in mmol/L.

Surprisingly, fluorescence quenching by the Au(III) complex 3a is more than 2 orders of magnitude more effective (KSV = 4270 M–1) than quenching by CF3I (Figure 3). If propagating species terminate frequently, some critical concentration of Au(III) product exists that may impede productive energy transfer from an excited species, halting reinitiation of the chain reaction.

In light of Puddephatt’s report, Au(I) alkyl complexes, such as Me3PAuMe, clearly react with CF3I.[14] However, there is no mention of the dependence of light on this process, although if the reaction is photoinitiated, mechanism 1 would seem especially unlikely given the absence of a chromophoric aryl ligand in Puddephatt’s examples. To test this hypothesis, we irradiated Cy3PAuMe (9) in the presence of CF3I (Scheme 2). While 9 does not absorb above 300 nm (see SI), the reaction is quantitative in CD2Cl2 when irradiated with ambient light, and does not proceed in the dark. The oxidized product is unobservable, eliminating CH3I to generate Cy3PAuCF3 at room temperature.[22,23] In THF, the reaction generates excess HCF in THF3, presumably also from solvent H• abstraction by •CF3.

Scheme 2

Photochemical Oxidative Addition of CF3I to 9 in CD2Cl2 and Spontaneous Reductive Elimination of CH3I

If initiation mechanism 2 is operative, then •CF3 could be generated by irradiating CF3I solutions containing electron donors other than Au(I), such as phosphines (Scheme 3).[24] Indeed, irradiation of PMe3 or PCy3 in the presence of CF3I results in formation of [Me3P-CF3]I (10a, 2JP–F = 63 Hz) or [Cy3P-CF3]I (10b,2JP–F = 42 Hz);[25] neither reaction proceeds in the dark. Consistent with quenching of [CF3I]* by Au(III), the oxidation of PCy3 in THF stalls at roughly 45% conversion (by 31P NMR) in the presence of 25 mol % Au(III) complex 3a.

Scheme 3

Photochemical Oxidation of Trialkylphosphines by CF3I

PPh3 does not react with CF3I (eq 3), presumably due to its lower oxidation potential relative to PMe3 and PCy3. When PCy3 and PPh3 are irradiated together with CF3I, only PCy3 is consumed, suggesting that PPh3 neither initiates the chain nor reacts with •CF3 during propagation. Contrary to our initial hypothesis that bulky phosphine ligands prevent aryl group transfer upon Au(I) oxidation, we found that Ph3PAu(4-F-C6H4) (11a) undergoes quantitative photoinitiated reaction with CF3I in CD2Cl2 to generate 12a (eq 4). Since PPh3 is unreactive toward CF3I, oxidation of 11a cannot be initiated by small amounts of dissociated PPh3 (we cannot disprove the analogous mechanism for PCy3-supported complex 1a.) Complex 12a was characterized by X-ray crystallography and shown to be isostructural to 3a (Figure 1B).

On the basis of these results, we propose that while photoexcited [CF3I]* undergoes rapid C–I bond homolysis and recombination, it also oxidizes Au(I) aryl and alkyl complexes by accepting electrons into a low-lying SOMO to generate radical anion [CF3I]•– (mechanism 2, Scheme 1). Homolysis of the C–I bond of [CF3I]•– generates iodide and •CF3, which oxidizes (R3P)AuR′ (6) to Au(II) intermediate 7. Iodine atom abstraction of CF3I by 7 affords Au(III) complex 8 and regenerates •CF3. In THF, oxidation of 6 by •CF3 is competitive with solvent H• abstraction to make HCF3 and terminate the radical chain. At sufficiently high concentrations, the Au(III) product (8) quenches [CF3I]* before it can reinitiate the radical chain reaction.

Promisingly, the photoinitiated oxidative addition of CF3I is general for electronically diverse complexes of the type Cy3PAu(aryl) (Tables 1 and 2). The resulting Au(III) products (see Figure 1 for their crystallographic analyses) can be purified by chromatography on silica. Complex 1b (aryl = 3,5-F2-C6H3), which is more electron-deficient than 1a (aryl = 4-F-C6H4), reacts smoothly with CF3I to afford 3b. While complexes with more electron-rich ligands such as 1c (aryl = C6H5) and 1d (aryl = 4-Me-C6H4) also react with CF3I to afford 3c and 3d, respectively, the most electron-rich complex 1e (aryl = 4-MeO-C6H4) decomposes to Au nano particles and several CF3-containing Au(III) complexes in solution and solid state (no products of Caryl–I or Caryl–CF3 reductive elimination can be detected). Au(III) product 3e is detectable, however, and its decomposition can be slowed substantially by addition of MeCN upon concentration of the reaction, allowing its solution-state characterization. The mechanism of decomposition has not yet been identified, although we speculate that the electron-rich arene may encourage PCy3 dissociation at room temperature and subsequent aryl group transfer.

The complex 1f (aryl = 2-Me-C6H4) does not react with CF3I at all, suggesting that CF3I oxidative addition is sensitive to the sterics of the aryl ligand and that relaxation of [CF3I]* is faster than oxidation of the metal center to initiate the radical chain. Unsurprisingly, no HCF3 is observed when 1f is irradiated in THF for 20 min.

Reductive Elimination from Au(III) Complexes

We next probed Caryl–CF3 reductive eliminations from Au(III). To our surprise, 12a undergoes quantitative Caryl–I reductive elimination in toluene-d8 at 110 °C to afford 4-fluoroiodobenzene and Ph3PAuCF3 over 20 min (Scheme 4).[22] No 4-fluoro(trifluoromethyl)benzene is observed by 19F NMR or GC. This process is highly sensitive to free phosphine, stalling completely in the presence of PPh3 (0.1 or 1.0 equiv) at 110 °C for 12 h. Treatment of 12a with PPh3-d15 at room temperature results in immediate formation of 12a-, presumably via an associative process.[2a−2d]

Scheme 4

Behavior of Au(III) Complex 12a and 12b in the Presence of Free PPh3 and at Elevated Temperatures

More electron-rich aryl ligands, such as 4-methylphenyl (12b), do not significantly affect the relative rates of Caryl–I and Caryl–CF3 reductive elimination (Scheme 4). At 110 °C, complex 12b undergoes mostly Caryl–I reductive elimination within 10 min to afford 4-methyliodobenzene.[26] Both Caryl–I and Caryl–CF3 reductive eliminations are also completely inhibited in the presence of PPh3 (0.1 or 1.0 equiv), while PPh3-d15 reacts immediately at room temperature to afford 12b-, also via associative ligand exchange. These observations are consistent with a mechanism involving highly reversible PPh3 dissociation from 12a and 12b, followed by slow Caryl–I reductive elimination from 13a or 13b, respectively.

Clearly, the behaviors of 12a and 12b are similar to Au(III)alkyl complexes studied by Kochi, which not only reductively eliminate Calkyl–Calkyl bonds between 70 and 100 °C via a dissociative mechanism but also undergo associative ligand exchange at ambient temperature with excess phosphine.[2a−2d] Unsurprisingly, analogous PCy3-stabilized complexes 3a and 3d are stable at 110 °C for at least 12 h, presumably due to the greater σ-donating ability of PCy3 relative to PPh3. Phosphine exchange with excess P(n-Bu)3, PBn3, or PCy3 does not occur even at these temperatures, precluding not only the lower-barrier associative exchange mechanism observed with the PPh3-supported systems (attributed to the larger cone angle of PCy3 relative to PPh3), but also PCy3 dissociation to form a three-coordinate complex.

Because Caryl–I reductive elimination is significantly faster than Caryl–CF3 reductive elimination, a cycle for gold-catalyzed trifluoromethylation must necessarily involve iodide abstraction from the Au(III) product of CF3I oxidative addition. Despite the apparent kinetic stabilities of the Au(III) complexes 3a–3e, 12a, and 12b, they all undergo quantitative Caryl–CF3 reductive elimination in less than 1 min upon treatment with AgSbF6at room temperature.

To consider the effects of the phosphine ligand on the silver-mediated Caryl–CF3 reductive elimination of Au(III), we used variable-temperature NMR to follow the reductive elimination from 3a and 12a in the presence of AgSbF6. PCy3-substituted complex 3a undergoes very fast (quantitative conversion in less than 1 min) Caryl–CF3 reductive elimination at −10 °C, while the analogous PPh3-stabilized 12a reacts similarly fast at room temperature (eq 5). At lower temperatures, several bridging species (most likely dimers) are observed by 19F NMR upon halide abstraction in both cases. If Caryl–CF3 bond reductive elimination can only occur from a monomeric three-coordinate intermediate, then 12a might be expected to undergo slower reductive elimination due to slower dimer dissociation and/or a dimer–monomer equilibrium that more favors the dimer, based on the smaller cone angle and weaker σ-donation of PPh3 relative to PCy3.

Conclusion

These results reported herein support the oxidative addition of CF3I to Au(I) via a photoinitiated chain reaction. The reactions are fast at room temperature for both Au(I) aryl and alkyl complexes. Aryl-CF3 reductive elimination is typically a high-barrier process but occurs in seconds at room temperature from a Au(III) cation. The Au(I)aryl species may be regenerated via one of the numerous transmetalation strategies available involving carbon nucleophiles.[27] For instance, excess (4-F-C6H4)SnMe3 (10 equiv) undergoes fast, quantitative transmetalation with [Cy3PAu]SbF6 at room temperature to afford 1a, thereby closing a hypothetical catalytic cycle based on the three elementary steps shown in Scheme 5. Silver-free halide abstraction from Au(III) complexes could conceivably enable a practical and mild cycle for gold-catalyzed trifluoromethylation of aryl nucleophiles, although deleterious reactions between starting material and metalloradical intermediates and •CF3 must be mitigated, as well as competitive aryl–aryl homocoupling.

Scheme 5

Oxidation of 1a, Aryl-CF3 Reductive Elimination, and Regeneration of 1a Supports the Feasibility of a Mild, Catalytic Trifluoromethylation

While we initially set out to probe Caryl–CF3 reductive elimination at Au(III), we also explored the oxidative addition of CF3I to Au(I), a process with potential implications beyond gold chemistry. The possibility of photoinitiated oxidation of transition metals or main group elements by CF3I should not be discounted in methods employing this reagent as a trifluoromethyl source, particularly since ambient fluorescent laboratory lighting is sufficient to initiate a chain in the presence of a suitable reductant. The results presented also suggest that substrate photoexcitation may provide a low-barrier avenue to kinetically challenging oxidative additions by Au(I), providing access to potentially reactive Au(III) complexes.[28]