Photochemical Reactions of Fluorinated Pyridines at Half-Sandwich Rhodium Complexes: Competing Pathways of Reaction.

Irradiation of CpRh(PMe3)(C2H4) (1; Cp = η5-C5H5) in the presence of pentafluoropyridine in hexane solution at low temperature yields an isolable η2-C,C-coordinated pentafluoropyridine complex, CpRh(PMe3)(η2-C,C-C5NF4) (2). The molecular structure of 2 was determined by single-crystal X-ray diffraction, showing coordination by C3-C4, unlike previous structures of pentafluoropyridine complexes that show N-coordination. Corresponding experiments with 2,3,5,6-tetrafluoropyridine yield the C-H oxidative addition product CpRh(PMe3)(C5NF4)H (3). In contrast, UV irradiation of 1 in hexane, in the presence of 4-substituted tetrafluoropyridines C5NF4X, where X = NMe2, OMe, results in elimination of C2H4 and HF to form the metallacycles CpRh(PMe3)(κ2-C,C-CH2N(CH3)C5NF3) (4) and CpRh(PMe3)(κ2-C,C-CH2OC5NF3) (5), respectively. The X-ray structure of 4 shows a planar RhCCNC-five-membered ring. Complexes 2-5 may also be formed by thermal reaction of CpRh(PMe3)(Ph)H with the respective pyridines at 50 °C.

Introduction

There has been substantial recent progress in C–F bond activation of aromatic and alkene C–F bonds in both stoichiometric and catalytic reactions.[1] Transition-metal-mediated C–F bond activation holds out the prospect of new ways of making fluorocarbons. It has also been found to be an excellent method of generating metal fluoride complexes.[1e] The analogy to C–H bond activation is tempting, but the contrasts can also be revealing. While cyclometalation via C–H bond activation is common, few examples of cyclometalation via C–F activation have been reported.

Albrecht reviewed cyclometalation reactions using d-block transition metals, showing many examples of metallacycles successfully applied in organic transformations, in catalysis and in various other domains of materials science.[2] Since then, many other papers have been published presenting characterizations of new metallacycles,[3] applications in hydrodefluorination catalysis,[4] oxygen sensing,[5] and transfer hydrogenation.[6]

C–F activation reactions to form a metallacycle have been achieved thermally using a Co(I) center with an aldazine N atom as an anchoring group to afford an ortho-chelated cobalt(III) complex containing a [C–Co–F] fragment;[7] Li and co-workers also reported a reaction where a cobaltacycle is formed after C–F activation and new fluoro-organics are formed by subsequent carbonylation reactions.[8] OsO4 reacts in the presence of HSR (R = C6F5, C6F4H-4) to afford different metallacycles through a process involving the rupture of one or two C–F bonds.[9] Love et al. have also demonstrated the activation of a C–F bond in the position ortho to an imine substituent of polyfluorinated arenes at platinum. Formation of a cyclometalated Pt complex leads to the methylation of polyfluorinated aryl imines by subsequent transmetalation and reductive elimination steps.[10] In all of these reactions, the ligands coordinate to the metal center first through the heteroatom (N or S) and the C–F bond is cleaved subsequently. A metal fluoride is detected in all the preceding examples except the osmium complex, either as the final product or as an intermediate in the catalytic cycle. No formation of HF has been detected or mentioned as a side product in any of these publications.

The use of rhodium for C–F activation reactions has been recently reviewed by Braun et al.;[1d] phosphine–rhodium complexes show particular effectiveness in C–F activation. Yamaguchi and co-workers reported C–F activation of fluorinated arenes and pyridines at rhodium centers;[11] Braun et al. found that RhH(PEt3)3 is capable of stoichiometric C–F activation in the 4-position of pentafluoropyridine.[12] More recently, they also prepared a 16-electron Rh(I) boryl complex, capable of ortho C–F activation of pentafluoropyridine. Calculations suggested a boryl-assisted mechanism and showed that the regioselectivity derives from nitrogen participation in the transition state.[13] Attack on a η5-pentamethylcyclopentadienyl rhodium(III) complex occurred at the less activated position, meta to the ring nitrogen atom, of a tetrafluoropyridyl substituent of a coordinated N-heterocyclic carbene.[14]

The photochemistry of CpRh(PMe3)(C2H4) (1, Cp = η5-C5H5; Scheme 1) has already been explored extensively at room temperature. Upon photolysis, loss of ethene leads to the formation of an unsaturated 16-electron complex capable of activating a wide range of bonds.[15] It reacts with benzene to yield CpRh(PMe3)(C6H5)H via a short-lived η2-arene complex. Photolysis with C6F6 results in the isolation of the stable η2-hexafluorobenzene complex CpRh(PMe3)(C6F6),[16] and reaction in pentafluoroanisole generates the metallacycle CpRh(PMe3)(κ2-C,C-CH2OC6F4), characterized by multinuclear NMR spectroscopy; reaction of this complex with 1 equiv of [Ph3C]+[PF6]− at 220 K generates [Cp(PMe3)Rh=C(H)OC6F4]PF6.[17]

Scheme 1

Photoreactions of 1 with Fluorinated Arenes

C–F bond cleavage of hexafluorobenzene has been achieved in the reaction with Cp*Rh(PMe3)(C2H4) (Cp* = η5-C5Me5). C–F activation took place upon further photolysis following initial η2 coordination of hexafluorobenzene.[18] Studies in Ar matrices at 12 K confirmed that while CpRh(PMe3)(η2-C6F6) prefers to eliminate C6F6 to form the 16-electron fragment, the more crowded Cp*Rh(PMe3)(C2H4) produces the C–F activated product preferentially.[19] Both the thermally generated fragment Cp*Rh(PMe3) and the photochemically generated fragment CpRh(PMe3) react with fluorinated aromatic hydrocarbons to yield the C–H activated products Cp*Rh(PMe3)(arylF)H when an aromatic C–H bond is present.[20]

In this paper, we explore the behavior of complex 1 in the presence of pentafluoropyridine, 2,3,5,6-tetrafluoropyridine, and substituted analogues (Scheme 2, compounds a–d) to obtain information about coordination modes, substituent effects, and reaction mechanisms. Reaction with pentafluoropyridine (a) allowed us to isolate and characterize CpRh(PMe3)(η2-C5NF5) (2), whereas reaction with 2,3,5,6-tetrafluoropyridine (b) formed the C–H activated product CpRh(PMe3)(C5NF4)H (3) selectively. We report the formation of the two metallacycles 4 and 5 by intramolecular C–F activation of 4-substituted tetrafluoropyridines (c and d) at the Rh center.

Scheme 2

Fluorinated Heteroaromatics Investigated

Results

Irradiation of 1 with Pentafluoropyridine (a)

The irradiation of 1 in hexane with excess pentafluoropyridine (λ >290 nm, 8 h, room temperature) generates a large number of products. When the reaction is performed at low temperature (−20 °C), the formation of one complex is preferred, leading to an NMR yield for complex 2 of >60%. At early times, 2 is the only product detected by NMR spectroscopy. This product was purified by removal of 1 by sublimation followed by crystallization, giving an orange product characterized by multinuclear NMR spectroscopy, high-resolution EI mass spectrometry, and X-ray crystallography. The 31P{1H} NMR spectrum shows a resonance at δ 3.09, as a doublet of doublets of doublets (JRhP = 192, JPF = 56, 52 Hz). The value of JRhP indicates a Rh(I) oxidation state,[16] and the large values of JPF are similar to those for Rh(η2-C6F6) complexes.[16] We therefore assign complex 2 as CpRh(PMe3)(η2-C4F5N) with the pentafluoropyridine bonded in an η2-C,C mode. The distinction between coordination at C3–C4 and C2–C3 may be made through the 19F NMR spectrum. The 19F{31P} NMR spectrum allowed the exact assignments for the five inequivalent fluorines on the pyridine ring. The two fluorines close to N (F2, F6) resonate at lower field at δ −55.5 and δ −119.8, F5, which is not involved in the η2 coordination, resonates at δ −155.7, and the two remaining fluorines appear at δ −157.3 (F4) and δ −169.0 (F3) (Scheme 3). Changes in splitting pattern on decoupling from 31P were observed just for F3 and F4, confirming that these two fluorines are bound to the coordinated carbons involved in η2 coordination. The evidence from NMR spectroscopy indicates that the pentafluoropyridine is coordinated in a η2-C3,C4 fashion. Selected NMR data for complex 2 are given in Table 1.

Scheme 3

Photochemical Formation of 2

Table 1

NMR Data (δ (J/Hz)) in C6D6 for the Precursor and Photoproducts

	31P{1H}	1H	19Fa
1	4.4 (d, JRh–P = 200)	0.77 (d, JP–H = 9.2, PMe3), 2.74 (m, C2H4), 1.46 (m, C2H4), 5.09 (s, Cp)
2	3.0 (ddd, JRh–P = 192, JP–F = 56, 52)	0.79 (d, JP–H = 10.5, PMe3), 4.37 (s, Cp)	–55.5 (m, F2), −119.8 (t, JF–F = 11.4, F6), −155.7 (tdd, JF–F = 11.4, 15.3, 34.3, F5), −157.3 (m, F4), −169.0 (m, F3)
3	12.6 (d, JRh–P = 142)	–12.9 (dd, JP–H = 22.8, JRh–H = 40, Rh–H), 1.35 (d, JP–H = 10.9, PMe3), 5.25 (s, Cp)	–100.7 (m, F3 and F4), −113.6 (m, F2 and F5)
4	13.8 (d, JRh–P = 158)	0.65 (d, JP–H = 10.6, PMe3) 2.96 (d, JH–H = 2.9, CH3), 3.04 (ddd, JP–H = 1.9, JRh–H = 6.7, JH–H = 16.1, HA, CH2), 4.87 (d, JRh–H = 1.3, Cp), 4.98 (dd, JH–H = 4.9, 6.7, HB, CH2)	–66.5 (dd, JF–F = 12.7, 23.7, F2), −100.1 (dd, JF–F = 12.7, 23.7, F3), −180.2 (t, JF–F = 23.7, F4)
5	14.0 (d, JRh–P = 159)	0.54 (d, JP–H = 10.5, PMe3), 4.73 (d, JRh–H = 1.3, Cp), 5.12 (ddd, JP–H = 1.42, JRh–H = 5.40, JH–H = 17.4, HA, CH2), 6.77 (m, HB)	–64.6 (dd, JF–F = 13.8, 21.4, F2), −99.1 (dd, JF–F = 13.8, 21.4, F3), −172.0 (t, JF–F = 21.4, F4)

The fluorine atoms are numbered as for the corresponding X-ray structures. For 5, we follow the numbering of 4.

The crystal structure of 2 shows the coordination of pentafluoropyridine but is complicated by disorder between the C6 (and F6) and the N1 of the pyridine ring (Figure 1a). The occupancies of the two conformers refined to 0.690:0.310(12). The structure of 2 shows a planar C5NF3 unit with the two C–F bonds involved in the η2 coordination bent out of the plane by 42.09(2)° (Figure 1b) in comparison to 43.8° for the Rh(η2-C6F6) analogue reported previously.[16] Similarly, the angle between the planes RhC(3)C(4) and C(2)C(3)C(4)C(5)C(6)N(1) is 106.70(16)° in comparison to 108.6° for the Rh(η2-C6F6) analogue. These interplane angles have been demonstrated to be very characteristic of M(η2-C6F6) complexes.[21] All the earlier crystal structures of coordinated pentafluoropyridine show the ligand bound through N, rather than η2-C,C as here.[22] Johnson et al. have recently reported extensive NMR characterization of η2-coordinated pentafluoropyridine and tetrafluoropyridine at a nickel center.[23] Such complexes have often been proposed as intermediates in C–F activation reactions (see the Discussion).[16,17]

Figure 1

(a) Molecular structure of 2. Hydrogen atoms are omitted for clarity. Ellipsoids for the anisotropic displacement parameters are shown at the 50% level. (b) Diagram showing interplane angles of the Rh(η2-C5NF5) unit. (c) Diagram of bond lengths (Å) for the η2-coordinated pyridine moiety (major conformer). Other bond lengths (Å): C(3)–Rh(1) 2.042(5), C(4)–Rh(1) 2.049(5), P(1)–Rh(1) 2.2732(10), C(2)–F(2) 1.332(6), C(3)–F(3) 1.382(6), C(4)–F(4) 1.381(5), C(5)–F(5) 1.339(6), C(6)–F(6) 1.310(6).

The coordinated C–C bond is extended to 1.442(7) Å. This may be compared to 1.379(4) Å for free C5NF5 determined in a solvate for the Tp′Rh(C5NF4)(PMe3)FHF complex.[24] A diene pattern is observed for the uncoordinated C–C bonds of 2 (Figure 1c). The C–F bonds in the coordination positions (3 and 4) average 1.382(7) Å, an extension of about 0.05 Å in comparison to the C–F bond length of free pentafluoropyridine (average 1.332(3) Å).[24]

Irradiation of 1 with 2,3,5,6-Tetrafluoropyridine (b)

The irradiation of 1 in C6D12 with excess 2,3,5,6-tetrafluoropyridine (b) (λ >290 nm, 8 h, room temperature) leads to the clean formation of product with a hydride resonance at δ −12.9 (dd, JP–H = 22.8, JRh–H = 40.0 Hz, Rh–H) and a doublet at δ 12.6 (d, JP–Rh = 141.9 Hz) in the 31P{1H} NMR spectrum, which was identified as CpRh(PMe3)(C5NF4)H (3). The 19F NMR spectrum is consistent with two sets of equivalent fluorines in a 1:1 ratio, indicating unrestricted rotation about the Rh–C(pyridyl) bond. The NMR data are consistent with those found for the reaction of CpRh(PMe3)(C2H4) with partially fluorinated arenes.[20] Colorless crystals were grown by slow evaporation from hexane, and the crystal structure was determined (Figure 2). The hydride was located by a difference map. Treatment of 3 with CCl4 resulted in the disappearance of the hydride resonance and formation of CpRh(PMe3)(C5NF4)Cl (3-Cl), which was also characterized by NMR spectroscopy and EI mass spectrometry. The 31P{1H} NMR spectrum of complex 3-Cl shows a doublet of triplets at δ 12.0 (t, JP–F = 8.3, JP–Rh = 133.3 Hz); the 19F NMR spectrum shows two sets of equivalent fluorines at δ −98.2 and –113.7.

Figure 2

Molecular structure of 3. Principal bond distances (Å): Rh(1)–C(1) 2.0363(18), Rh(1)–H(1) 1.53(3), Rh(1)–P(1) 2.2237(5). Principal angles (deg): C(1)Rh(1)P(1) 88.45(5), C(1)Rh(1)H(1) 87.3(12). Hydrogen atoms other than hydride are omitted for clarity. Ellipsoids for the anisotropic displacement parameters are shown at the 50% level.

Irradiation of 1 with 4-Dimethylamino-2,3,5,6-tetrafluoropyridine (c)

The irradiation of 1 in hexane (λ >290 nm, 8 h, room temperature) with the excess substituted tetrafluoropyridine 4-dimethylamino-2,3,5,6-tetrafluoropyridine (c) generates the metallacycle CpRh(PMe3)(κ2-C,C-CH2N(CH3)C5NF3) (4) with an NMR yield of 85% (Scheme 4). When the reaction was scaled up, the complex crystallized out of the reaction mixture during photolysis as an isolable, air-stable, pale orange solid. The 1H NMR spectrum shows the CH2 protons of the metallacycle 4 to be diastereotopic, because it is bonded to a stereogenic Rh center. The two resonances are correlated by COSY NMR spectroscopy and appear at δ 3.04 (ddd) and at δ 4.87 (m) with different P–H and H–H coupling constants.

Scheme 4

Photochemical Reaction of 1 with c and d

This very low field chemical shift for the diastereotopic proton compares with shifts of δ 6.82 and 5.24 for the diastereotopic proton of the complex CpRh(PMe3)(κ2-C,C-CH2OC6F4) previously observed.[17] The 31P{1H} NMR spectrum displays a doublet with a coupling constant typical of a Rh(III) species (δ 13.8, JPRh = 158 Hz).[15b] The 19F NMR spectrum displays three different peaks for the three inequivalent fluorines, two at lower field for the fluorines ortho to nitrogen and one at higher field. Finally, the 13C DEPT spectrum of 4 confirms that the resonance at δ 40.3 arises from a CH2 group (dd JCRh = 29.8 Hz, JCP = 13.8 Hz). A complete set of chemical shifts and coupling constants is given in Table 1.

Complex 4 was isolated as small pale orange crystals by crystallization from hexane, and its structure was determined by X-ray crystallography (Figure 3). The five-membered rhodacycle is planar, as confirmed by the sum of the internal angles (539.89°). It is also coplanar with the pyridine ring fused to it.

Figure 3

Molecular structure of 4. Principal bond distances (Å): C(1)–Rh(1) 2.023(3), C(6)–Rh(1) 2.069(3), Rh(1)–P(1) 2.2311(7), C(1)–C(5) 1.422(3), C(6)–N(2) 1.463(3), C(5)–N(2) 1.346(3). Principal angles (deg): P(1)–Rh(1)–C(6) 89.60(8), P(1)–Rh(1)–C(1) 87.87(7). Hydrogen atoms are omitted for clarity. Ellipsoids for the anisotropic displacement parameters are shown at the 50% level.

Irradiation of 1 with 4-Methoxy-2,3,5,6-tetrafluoropyridine (d)

The irradiation of 1 in hexane (λ >290 nm, 6 h, room temperature) with excess substituted tetrafluoropyridine 4-methoxy-2,3,5,6 tetrafluoropyridine (d) generates the metallacycle CpRh(PMe3)(κ2-C,C-CH2OC5NF3) (5) with an NMR yield of 20%. The formation of 5 appeared to be limited by a dark film formed on the wall of the tube. Low-temperature (−20 °C) photolysis and use of a λ >350 nm UV filter did not improve the conversion. The 1H NMR spectrum again shows the CH2 protons of the metallacycle 5 to be diastereotopic. The two resonances appeared at lower field than those observed for 4: δ 5.25 (ddd) and 6.90 (m). Complex 5 was isolated as small pale orange crystals by crystallization from hexane. A crystal structure determination was attempted, but the refinement never converged satisfactorily because of twinning. Nevertheless, the identity of complex 5 was confirmed.

Thermal Reactions of CpRh(PMe3)(Ph)H (6) with a–d

The irradiation of 1 in neat C6H6 formed the C–H activated product CpRh(PMe3)(Ph)H (6), as previously reported.[16] Complex 6 was used as a precursor to check if its thermal reactivity in hexane with excess fluoropyridines (10-fold) resulted in the same product distribution. The reaction of 6 with a at 50 °C was completed overnight to form complex 2 as the principal product. Conversion of 6 to complex 3 by reaction with b also proceeded under the same reaction conditions; an additional unidentified phosphorus-containing species was observed by 31P{1H} NMR spectroscopy. The same route was explored for complex 6 with excess c and d. The formation of the metallacycles 4 and 5 was confirmed along with the appearance of a mixture of unidentified side products observable by 19F and 1H nuclei spectroscopy. The new set of products, which were not observed by the photochemical route, remained unidentified.

Mechanistic Studies

Reaction with Pentafluoropyridine

Photochemical reaction of complex 1 with pentafluoropyridine produces a mixture of compounds: complex 2 was identified as the only one with a coupling constant JPRh characteristic of Rh(I); all the rest are Rh(III) species. The selectivity toward formation of 2 was achieved by performing photolysis at low temperature in hexane with a 10-fold excess of pentafluoropyridine. Variable-temperature NMR spectroscopy (210–320 K) was performed in order to look for any other isomers, but no new compounds were detected, confirming that the reaction is regioselective toward the C(3)–C(4) position. When the reaction was monitored in situ, a hydride resonance was detected at δ −12.42 (dd, JP–H = 39.9 Hz, JRh–H = 22.9 Hz) which was identical to the hydride resonance of 3. Probably, reaction of C5NF5 with some species formed in the reaction mixture led to hydrodefluorination to form C5NF4H as already reported.[25] It is clear from these experiments that complex 2 is stabilized enough for isolation and that C–F oxidative addition certainly does not occur under mild conditions. The complex appeared to be stable in solution upon heating up to 100 °C. The reaction of 1 with 2,3,5,6-tetrafluoropyridine produces the C–H activation product cleanly in 100% NMR yield. Even when the irradiation was prolonged, no evidence for C–F activation was found and complex 3 was the only observed product.

Reaction of Complex 1 with 4-Substituted Tetrafluoropyridines

The photoreaction of 1 with 4-substituted tetrafluoropyridines C5NF4X (X = OMe, NMe2) yields metallacycles 4 and 5. We also investigated these reactions in NMR experiments to search for reaction intermediates. The expected byproduct, free HF, was observed in the 1H NMR spectrum as a low-field broad peak at δ 14.7 (see the Supporting Information). The photochemical reaction of 1 results in initial photodissociation of C2H4 from 1;[16] possible reaction intermediates could arise by coordination of the substrate by η2 coordination and/or C–F or C–H oxidative addition. The formation of 4 and 5 by thermal reaction of CpRh(PMe3)(Ph)H with c and d confirms that the photochemical step is elimination of C2H4 from 1 (see the Introduction) and that the remaining steps are thermal in origin. When the reaction is conducted in hexane or in cyclohexane-d12 and followed by 1H NMR spectroscopy, a hydride is detected at δ −14 (dd, JP–H = 38.6, JRh–H = 28.9 Hz) as a minor product in addition to the metallacycle. The hydride was identified as CpRh(PMe3)H2 by comparison with previous work.[26] When the reaction was followed by 31P and 19F NMR spectroscopy, we did not notice any evidence of a Rh(I) complex characteristic of η2 coordination or a 19F resonance at high field characteristic of a fluoride complex. Even when the reaction was carried out at 253 K and the NMR spectrum taken at 200 K, no such species were observed. In contrast, it was established previously that cyclometalation occurred via η2 coordination on photoreaction of 1 with C6F5OMe.[16,17]

In order to elucidate the role of the substituent on the fluoropyridine ring, we also examined the photoreactions of 1 with 4-ethyltetrafluoropyridine and with 4-ethoxytetrafluoropyridine. Neither reaction showed any cyclometalated products. We conclude that cyclometalation requires a heteroatom substituent and a primary C–H bond as in −NMe2 or −OMe. The preference for the metal center to activate a primary C–H bond has already been observed by Jones et al.[27] We also investigated the addition of CsF as a base to trap HF: it neither promoted the formation of the cyclometalated species nor inhibited it. However, we note that a weak base is present in the form of excess 4-substituted pyridine (see the Discussion).

The kinetic isotopic effect was also explored. A large isotopic effect was reported for an Ir-PCP/4-methoxy-2,3,5,6-tetrafluorotoluene system to form the C–O activated product where neither a direct oxidative addition nor a simple SN2 mechanism was observed.[28] The deuterated analogue of 2,3,5,6-tetrafluoro-4-methoxypyridine, C5NF4OCD3, was synthesized and characterized by NMR spectroscopy, mass spectrometry, and IR absorption (see the Supporting Information). The irradiation of 1 in hexane with excess of both substituted tetrafluoropyridines d and d–OCD3, present in a 1:5:5 ratio (λ >290 nm, 12 h, room temperature) generates a mixture of the metallacycles CpRh(PMe3)(κ2-C,C-CH2OC5NF3) (5) and the deuterated analogue CpRh(PMe3)(κ2-C,C-CD2OC5NF3) (6) with an NMR yield of 30%. Since the 19F and 31P{1H} NMR spectra of the two cyclometalated species are coincident, EI mass spectrometry was employed to determine the KIE. Reproducible results were obtained from two parallel experiments that showed a product ratio of 0.94 ± 0.04. We conclude that the KIE is very small.

Discussion

The reactions of 1 with n class="Chemical">fluorinated pyridines are summarized in Scheme 5. The current experiments demonstrate the formation by photochemical reaction of CpRh(PMe3)(η2-C3,C4-C5NF5) as an isolable solid. Reaction with 2,3,5,6-tetrafluoropyridine is selective for C–H activation. Use of NMe2 and OMe substituents on the fluoropyridine results in cyclometalation to form new air-stable rhodacycle species by both C–H and C–F insertion (Scheme 5).

Scheme 5

Reactions of Complex 1 with Fluorinated Pyridines

Pentafluoropyridine is a weak nitrogen base. According to DFT calculations, the HOMO is the a2 ring π orbital with a node through nitrogen, and the nitrogen lone pair appears as the HOMO-1 or HOMO-2 (according to the method). The LUMO is the 3b1 π* orbital.[29] The photoreaction of 1 with pentafluoropyridine to form the η2-C,C-coordinated complex 2 may be contrasted with other reactions of pentafluoropyridine, which reveal a wide variety of modes of coordination and activation. The reaction of (dfepe)PtMe2 with (1,3,5-C6H4Me3)+B(C6F5)4– (dfepe = (C2F5)2PCH2CH2P(C2F5)2) in the presence of C5NF5 and that of [(tmeda)Pt(CH3)2] (tmeda = N,N,N′,N′-tetramethylethylenediamine) with [C5NF5H]BArF4 yield N-coordinated products.[22a,22b] Nitrogen coordination of pentafluoropyridine was also observed for cis-[Re(PR3)(CO)4(L)][BArF4][30] and [CF3PCPPt(C5NF5)]+ (where CF3PCP = (1,3-C6H4(CH2P(CF3)2)2).[31] C–F oxidative addition takes place on reaction of Ni(COD)2 in the presence of excess of PEt3 and pentafluoropyridine, leading preferentially to an ortho-activated trans-Ni(F)(2-C5NF4)(PEt3)2 complex.[32] However, the activation takes place at the para position when the phosphine is replaced by a carbene.[33] DFT calculations based on the model Ni(PMe3)2 suggest that the ortho regioselectivity derives from a neighboring group effect with participation of the phosphine and the nitrogen of the pentafluoropyridine.[34] Johnson explored the reactivity of the phenanthrene adduct (PEt3)2Ni(η2-C14H10) toward pentafluoropyridine; both the mononuclear adduct (PEt3)2Ni(η2-C,C-C5NF5) and the analogous dinuclear adduct [(PEt3)2Ni]2(μ-η2:η2-C,C-C5NF5) were characterized in solution, confirming that coordination precedes C–F activation.[23] Para C–F activation of pentafluoropyridine with Pt(PCy3)2 and Pd(PCy3)2 forms the tetrafluoropyridyl products through two different mechanisms: phosphine assistance for the platinum complex and C–F oxidative addition for the palladium species.[35]

In order to explore the preference for C–H compared to C–F activation, the reaction of complex 1 with 2,3,5,6-tetrafluoropyridine was investigated. It produces the C–H activated product 3 cleanly, in contrast to Ni(COD)2, where C–F activation was preferred to form the ortho C–F activated species as the major product.[32] Recently Johnson and co-workers isolated the C–H activated product of tetrafluoropyridine as the major species for reaction of the phenanthrene adduct (PEt3)2Ni(η2-C14H10) at temperatures lower than 193 K, demonstrating that small changes in reaction conditions could drastically influence the selectivity.[23]

The introduction of an NMe2 or OMe substituent on the pyridine leads to cyclometalation by C–F and C–H activation with concomitant elimination of HF. The role played by the substituent is crucial in reactions of complex 1 with 4-substituted fluorinated pyridines. Different reactivity is shown employing complex 1 in reactions with ethoxy- and ethyltetrafluoropyridines, showing that the complex needs a primary carbon as in OMe or NMe2 to cyclometalate as well as the presence of the heteroatom on the substituent. In contrast, the same pyridines react at Ni(PEt3)2 to give C–F oxidative addition at the 2-position, reactivity analogous to that shown by pentafluoropyridine toward Ni(PEt3)2.[36]

To our knowledge, there are few reported reactions which eliminate HF from a single substrate in a manner similar to the cyclometalation reactions above. Since HF has an exceptionally large bond dissociation energy, its formation will act as a thermodynamic driver. The reaction is likely to be initiated by coordination of the 4-substituted pyridine, followed by either C–F oxidative addition or C–H oxidative addition. It was already established that the CpRh(PMe3) fragment selectively activates C–H bonds over C–F bonds.[20] The C–F oxidative addition product with hexafluorobenzene was observed only in low-temperature matrices.[19] η2 coordination takes place for the reaction of the same Rh fragment with methoxypentafluorobenzene. The reaction then proceeds through a cyclometalation pathway, liberating HF (Scheme 1). Displacement of HF and ring closure gives rise to the cyclometalated species, but the detailed mechanism of HF elimination is unknown.[17]

Three mechanisms have been proposed to explain the formation of HF in related reactions: electron transfer or nucleophilic attack of two different types (Scheme 6). Notably, all three reactions start from metal hydride complexes. Ru(dmpe)2H2 was proposed to react at −78 °C with hexafluorobenzene to give the pentafluorophenyl hydride complex through an electron-transfer process where HF is lost (Scheme 6, path 1).[37] Cp*Rh(PMe3)H2 activates the C–F bond of a variety of fluoroaromatics thermally by a nucleophilic aromatic substitution. Either pyridine or fluoride acts as base to produce the metal anion, the active species in the C–F activation. HF is produced in this reaction together with the C–F activated product (Scheme 6, path 2).[38] Recently, DFT studies on the reaction of Ru(NHC)(PPh3)(CO)H2 in the presence of fluorinated arenes indicated a novel mechanism where a metal hydride reacts intermolecularly with C6F5H by ortho-selective nucleophilic attack to form HF (Scheme 6, path 3).[39]

Scheme 6

Mechanism Where HF Is Eliminated To Form the Products: (1) Electron Transfer; (2) Base-Assisted Nucleophilic Substitution; (3) Ortho-Selective Nucleophilic Attack

All of these examples suggest that the cyclometalation reactions described here proceed via C–H bond activation of 4-substituted pyridines at the NMe2 or OMe groups, even though we have not detected a significant KIE. Distinction between the three mechanisms outlined in Scheme 6 is not possible. A similar problem of the order of C–H and C–F bond activation is apparent in the photochemical reaction of Cp*Re(CO)3 with hexafluorobenzene. This reaction results in insertion into the C–F bond with concomitant C–H activation of a methyl of the Cp* ligand to form Re(η6-C5Me4CH2)(CO)2(C6F5) with HF elimination, but the mechanism is unknown.[40] Hydrodefluorination is usually carried out with fluoride acceptors such that generation of HF is avoided.[1i]

Conclusions

The behavior of transition-metal complexes toward fluorinated pyridines is remarkably diverse. In this paper, we have studied the reactivity of photochemically generated CpRh(PMe3) toward fluorinated pyridines. Pentafluoropyridine coordinates to CpRh(PMe3) in an η2-C,C mode, providing a crystallographically characterized example of a coordination mode implicated previously by NMR spectroscopy and by DFT calculations. In contrast, 2,3,5,6-tetrafluoropyridine undergoes C–H oxidative addition. The corresponding tetrafluoropyridine containing an NMe2 or OMe group at the 4-position reacts to form a cyclometalated product via combined C–H and C–F bond activation with HF elimination. These reactions contrast with the behavior of the same reagents toward rhenium, nickel, and platinum complexes, as discussed in detail above.

Experimental Section

General Procedures

All operations were performed under an argon atmosphere, on a high-vacuum line (10–4 mbar) using modified Schlenk techniques, on standard Schlenk (10–2 mbar) lines, or in a glovebox. Solvents for general use (hexane, benzene) were of AR grade, dried by distillation over classical reagents, and stored under Ar in ampules fitted with Young PTFE stopcocks. Hexane was collected from the purification system and dried again by distillation. Deuterated solvents were dried by stirring over potassium and were distilled under high vacuum into small ampules with potassium mirrors. Pentafluoropyridine and 2,3,5,6-tetrafluoropyridine were purchased from Sigma-Aldrich and dried over molecular sieves. Photochemical reactions, at room temperature, were performed in glass NMR tubes fitted with PTFE taps, using a 125 W medium-pressure mercury vapor lamp with a water filter (5 cm). UV–vis irradiation at lower temperatures was performed using a 300 W Oriel 66011 xenon lamp with a thermostatically controlled cooling system cooled by gaseous nitrogen boil-off. All NMR spectra were recorded on Bruker AMX500 spectrometers in glass tubes fitted with Young PTFE stopcocks. All 1H and 13C chemical shifts are reported relative to tetramethylsilane and are referenced using the chemical shifts of residual protio solvent resonances (benzene, δ 7.15 for 1H and δ 128.0 for 13C). 19F NMR spectra were recorded at 470.5 MHz and referenced to external CFCl3 at δ 0. The 31P{1H} NMR spectra were recorded at 202.5 MHz and are referenced to external H3PO4. EI mass spectra were measured on a Waters Micromass GCT Premier orthogonal time of-flight instrument. The LIFDI mass spectra were measured on the same instrument set to one scan per second with resolution power of 6000 fwhm and equipped with a LIFDI probe from LINDEN GmbH. The design is very similar to that described by Gross et al.[41] Toluene was used for tuning the instrument. The poly(ethylene glycol) probe was kept at ambient temperature with the emitter potential at 12 kV. Activated tungsten wire LIFDI emitters (13 μm tungsten from LINDEN) were ramped manually up to 100 mA for the emitter heating current during the experiment. m/z values are accurate to 0.01 Da. The IR experiments were performed using a Unicam RS 10000E FTIR instrument. The spectrum was recorded on a liquid film averaging 16 scans at 1 cm–1 resolution.

Diffraction data for CpRh(PMe3)(η2-C5NF5) were collected at 110 K on a Bruker Smart Apex diffractometer with Mo Kα radiation (λ = 0.71073 Å) using a SMART CCD camera. Diffractometer control, data collection, and initial unit cell determination was performed using SMART (v5.625 Bruker-AXS). Frame integration and unit-cell refinement software was carried out with SAINT+ (v6.22, Bruker AXS). Absorption corrections were applied using SADABS (v2.03, Sheldrick). The structure was solved by direct methods using SHELXS-97 (Sheldrick, 1997) and refined by full-matrix least squares using SHELXL-97 (Sheldrick, 1997).[42] Diffraction data for CpRh(PMe3)(κ2-C,C-CH2N(CH3)C5NF3) and CpRh(PMe3)(C5NF4)H were collected at 110 K on an Agilent SuperNova diffractometer with Mo Kα radiation (λ = 0.71073 Å). Data collection, unit cell determination, and frame integration were carried out with “CrysalisPro”. Absorption corrections were applied using crystal face indexing and the ABSPACK absorption correction software within CrysalisPro. Structures were solved and refined using Olex2[43] implementing SHELX algorithms. Structures were solved by either Patterson or direct methods using SHELXS-97 and refined by full-matrix least squares using SHELXL-97. All non-hydrogen atoms were refined anisotropically. Carbon-bound hydrogen atoms were placed at calculated positions and refined using a “riding model”. Crystallographic parameters for 2–4 are given in Table S1 (Supporting Information).

Synthesis and NMR Experiments

CpRh(PMe3)(n class="Chemical">C2H4) was synthesized by literature procedures, but replacing TlCp by LiCp.[44] 4-Dimethylamino-2,3,5,6 tetrafluoropyridine and 4-methoxy-2,3,5,6-tetrafluoropyridine were also synthesized by literature procedures.[45] The pyridines were additionally characterized by NMR spectroscopy and EI mass spectrometry. NMR yields were determined by 31P NMR spectroscopy as product integration/total integration.

Preparation of CpRh(PMe3)(η2-C5NF5) (2)

An 8 mm diameter NMR tube, fitted with a Young tap, was charged with complex 1 (50 mg) and pentafluoropyridine (2 fold excess) in hexane and irradiated at −20 °C with the Oriel Xe arc (8 h), resulting in 60% conversion to 2. The excess of pentafluoropyridine and solvent were pumped down under vacuum, and part of the unreacted starting material and other products were sublimed at 25 °C and 1 × 10–4 mbar onto a liquid nitrogen cold finger, leaving a brown residue. The brown residue was suspended in dry hexane, heated to 60 °C, and filtered under argon. The orange solution was then cooled to −20 °C for a few days to obtain small orange crystals of complex 2.

1H NMR (C6D6, 300 K): δ 4.37 (s, 5H, C5H5), 0.79 (d, 9H, JP–H = 10.6 Hz, PMe3). 31P{1H} NMR: δ 3.09 (ddd, JRh–P = 192, JP–F = 56, JP–F = 52 Hz). 13C{1H} NMR: δ 91.44 (t, C5H5), 21.90 (d, JP−C = 31 Hz, PMe3); there is no indication in the spectrum of carbons corresponding to the pentafluoropyridine ring. 19F NMR: δ −55.5 (m, 1F, F2), −119.8 (t, JF−F = 11.4, 1F, F6), −155.7 (tdd, JF−F = 11.4, 15.3, 34.3 Hz, 1F, F5), −157.3 (m, 1F, F4), −169.0 (m, 1F, F3). EI MS: m/z 412.9876 (M+) 100% (calcd for C13H14NF5PRh 412.9839, difference 0.4 mDa).

Preparation of CpRh(PMe3)(C5NF4)H (3)

An NMR tube, fitted with a Young tap, was charged with complex 1 (15 mg) and n class="Chemical">2,3,5,6-tetrafluoropyridine (2-fold excess) in C6D12 and irradiated at room temperature (8 h), resulting in 100% conversion to 3.

1H NMR (C6D12, 300 K): δ 5.25 (s, 5H, C5H5), 1.35 (d, JP–H = 13 Hz, 9H, PMe3), −12.42 (dd, JP–H = 40, JRh–H = 23 Hz, 1H, Rh–H). 31P{1H} NMR: δ 11.1 (dd, JRh–P = 142, JF–P = 22 Hz). 13C{1H} NMR: δ 87.46 (t, JC–P = 3 Hz, C5H5), 21.71 (dd, JC–P = 35, JC–Rh = 1.4 Hz, PMe3); there is no indication in the spectrum of carbons corresponding to the tetrafluoropyridine ring. 19F NMR: δ −100.67 (m, 2F, F meta to Rh), −113.7 (m, 2F, F ortho to Rh). MS (LIFDI, m/z): 395.01 (100%, M+), 393.99 (20%, [M+] – HF) exptl; 394.99 calcd for C13H15NPF4Rh. Anal. Calcd for C13H15NPF4Rh·0.15C5F4NH: C, 39.53; H, 3.65; N, 3.86. Found: C, 39.76; H, 3.73; N, 4.16.

Preparation of CpRh(PMe3)(C5NF4)Cl (3-Cl)

A solution of 1 and n class="Chemical">2,3,5,6-tetrafluoropyridine in 0.5 mL of hexane was irradiated in an NMR tube as described previously. Volatiles were then removed under vacuum, and the residue was redissolved in hexane. This solution was added to carbon tetrachloride (1 mL) under inert conditions at −20 °C. The mixture was maintained at −20 °C for 3 h, after which point the solvent was removed under vacuum. The crude product was dissolved in in C6D6 to obtain NMR characterization data.

1H NMR (C6D6, 300 K): δ 4.50 (d, Jn class="Chemical">Rh–H = 1.6 Hz, 5H, C5H5), δ 1.04 (d, JP–H = 11.8 Hz, 9H, PMe3). 31P{1H} NMR: δ 12.0 (dt, JRh–P = 133, JF–P = 9 Hz). 13C{1H} NMR: δ 88.7 (dd, J = 3, 4 Hz, C5H5), δ 17.9 (dd, JC–P = 35 Hz, PMe3). 19F NMR: δ −98.20 (m, 2F, F3, F4), δ −113.7 (m, 2F, F2, F5). MS (LIFDI, m/z): 428.95 (100%, M+) exptl; 428.95 calcd for C13H14NClPF4Rh. EI MS: m/z 428.9544 (M+) 40% (calcd for C13H14N35ClPF4Rh 428.9544, difference 0.0 mDa), 392.9733 (100%, [M+] – Cl).

Preparation of CpRh(PMe3)(κ2-C,C-CH2N(CH3)C5NF3) (4)

An 8 mm diameter NMR tube, fitted with a Young tap, was charged with complex 1 (50 mg) and previously degassed 4-dimethylamino-2,3,5,6 tetrafluoropyridine (5-fold excess) in hexane and irradiated at room temperature (8 h), resulting in 85% conversion to 4. The excess of pyridine and solvent were pumped down under vacuum, and part of the unreacted starting material and other byproducts were sublimed at 25 °C and 1 × 10–4 mbar onto a liquid nitrogen cold finger, leaving a sticky brown residue. The brown residue was then washed with hexane (three times), dried, and dissolved in C6D6 in order to obtain NMR characterization data. Pure crystals appeared as light orange blocks at low T (−20 °C) from dry hexane. Suitable material for elemental analysis was obtained by washing the solid with a cold mixture of degassed ethanol and water.

1H NMR (C6D6, 300 K): δ 4.98 (dd, CH2, HbJH–Rh = 5, JH–H = 7 Hz), 4.87 (d, JRh–H = 1 Hz, C5H5), 3.04 (ddd, CH2, Ha, JP–H = 2, JRh–H = 7, JH–H = 16 Hz), 2.96 (d, CH3JH–H = 3 Hz), 0.65 (d, JP–H = 11 Hz, PMe3). 31P{1H} NMR: δ 13.8 (d, JRh–P = 158 Hz). 13C{1H} NMR: δ 89.5 (t, JC–P = 3 Hz, C5H5), 40.3 (ddd, JC–Rh = 30, JC–P = 15, JC–C = 1 Hz, CH2), 38.9 (dd, JC–P = 12, JC–C = 2 Hz, CH3), 17.5 (d, JC–P = 32 Hz, PMe3). 19F NMR: δ −66.5 (dd, JF–F = 13, 24 Hz, F2), −100.1 (dd, JF–F = 13, 24 Hz, F3), −180.2 (t, JF–F = 24 Hz, F4). EI MS: m/z 418.0299 (M+) 100% (calcd for C15H19N2F3PRh 418.0293, difference 0.6 mDa). IR (solid): ν(CF stretching and ring vibration)/cm–1 1600 (m), 1578 (m), 1435 (m), 0.1411 (m), 1339 (m), 1299 (m), 1288 (m), 1257 (w), 1180 (w), 1167 (m), 1145 (m), 1039 (m), 1018 (m), 1018 (m), 950 (s), 938 (s), 888 (w), 820 (m), 804 (s), 734 (m), 718 (m), 680 (m). Anal. Calcd for C15H19N2F3PRh: C, 43.08; H, 4.58; N, 6.70. Found: C, 43.21; H, 4.56; N, 6.54.

Preparation of CpRh(PMe3)(κ2-C,C-CH2OC5NF3) (5)

An 8 mm diameter NMR tube, fitted with a Young tap, was charged with complex 1 (50 mg) and previously degassed 4-methoxy-2,3,5,6 tetrafluoropyridine (5-fold excess) in hexane and irradiated at room temperature (6 h), resulting in 20% conversion to 4. The excess of pyridine and solvent were pumped down under vacuum, and part of the unreacted starting material and other byproducts were sublimed at 25 °C and 1 × 10–4 mbar onto a liquid nitrogen cold finger, leaving a brown sticky residue. The brown residue was then washed with hexane (three times), dried, and dissolved in C6D6 in order to obtain NMR characterization data. Crystals appeared as light orange blocks at low T (−20 °C) from dry hexane.

1H NMR (C6D6, 300 K): δ 6.77 (dt, CH2, n class="Chemical">1H, HbJH–H = 5, JH–Rh = 1 Hz), 5.1 (ddd, CH2, 1H, HaJP–H = 1, JRh–H = 6, JH–H = 18 Hz), 4.73 (d, JRh–H = 1 Hz, 5H, C5H5), 0.55 (d, JP–H = 10 Hz, 9H, PMe3). 31P{1H} NMR: δ 14.0 (d, JRh–P = 159 Hz). 13C{1H} NMR: δ 89.7 (t, JC–C = 3 Hz, C5H5), 17.9 (d, JC–P = 33 Hz, PMe3), 41 (ddd, JC–Rh = 30, JC–P = 14, JC–C = 1 Hz, CH2). 19F NMR: δ −64.6 (dd, JF–F = 14, 22 Hz, 1F, F2), −99.1 (dd, JF–F = 14, 22 Hz, 1F, F3), −172.0 (t, JF–F = 22 Hz, 1F, F4). EI MS: m/z 404.9975 (M+) 100% (calcd 404.9977, difference 0.2 mDa).