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Dec 19, 2008 - Alberico,. D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107 ...... dine with [MCl2Cp*]2 (M ) Rh, Ir) in the absence of sodium acetate...
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Organometallics 2009, 28, 433–440

433

Mechanistic Study of Acetate-Assisted C-H Activation of 2-Substituted Pyridines with [MCl2Cp*]2 (M ) Rh, Ir) and [RuCl2(p-cymene)]2 Youcef Boutadla, Omar Al-Duaij, David L. Davies,* Gerald A. Griffith, and Kuldip Singh UniVersity of Leicester, Leicester, U.K., LE1 7RH ReceiVed September 18, 2008

Reactions of 2-substituted pyridines HL with [MCl2Cp*]2 (M ) Ir, Rh) and [RuCl2(p-cymene)]2 have been carried out in the presence and absence of sodium acetate. 2-Phenylpyridine (HL1) is cyclometalated easily to form [MCl(L1)(ring)] 1a-c (M ) Rh, Ir, ring ) Cp*; M ) Ru, ring ) p-cymene). However, in the case of 2-acetylpyridine (HL2) sp3 CsH activation occurs cleanly with rhodium to form N,C chelate complex [RhCl(L2)Cp*] 2b, but the reactions with iridium and ruthenium give unseparable mixtures of products. The N,C cyclometalated products [MCl(L2)(ring)] 2a-c (M ) Ir, Rh, ring ) Cp*; M ) Ru, ring ) p-cymene) have been independently prepared from the lithium enolates of 2-acetylpyridine. Notably, in the absence of acetate, [RhCl2Cp*]2 shows no reaction with 2-acetylpyridine, whereas [IrCl2Cp*]2 and [RuCl2(p-cymene)]2 react to form equilibrium mixtures of the starting materials and N,O chelate complexes 4a,c, respectively. In the presence of KPF6 the N,O chelate complexes [MCl(HL2)(ring)][PF6] 4a,c,d (M ) Ir, ring ) Cp*; M ) Ru, ring ) p-cymene, mesitylene) can be isolated. These are not intermediates en route to the N,C cyclometalated products. These results suggest that for CsH activation to occur under these mild conditions acetate must coordinate to the metal prior to coordination of the ligand. Introduction Cyclometalation reactions have been known for a long time, the first platinum metal complex being reported in 1965.1 Since then, cyclometalated complexes have attracted considerable interest for a wide variety of applications.2 In recent years CsH activation to form a cyclometalated complex has become an integral part of many catalytic cycles,3 including rutheniumcatalyzed arylation4,5 or alkenylation6 of 2-phenyl-substituted pyridines or other N-heterocycles. In order to design better catalysts, a detailed understanding of the mechanism of the cyclometalation and factors affecting the CsH activation step are desirable. We have previously reported room-temperature cyclometalation of phenyl-substituted imines, oxazolines, and amines by [MCl2Cp*]2 (M ) Rh, Ir) and [RuCl2(p-cymene)]2 in the presence of sodium acetate.7 Subsequently in collaboration * Corresponding author. E-mail: [email protected]. (1) Cope, A. C.; Siekman, R. W. J. Am. Chem. Soc. 1965, 87, 3272–3. (2) Dupont, J.; Consorti, C. S.; Spencer, J. Chem. ReV 2005, 105, 2527– 2571. Ghedini, M.; Aiello, I.; Crispini, A.; Golemme, A.; La Deda, M.; Pucci, D. Coord. Chem. ReV. 2006, 250, 1373–1390. Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917–1927. Bedford, R. B. Chem. Commun. 2003, 1787–1796. (3) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826–834. Alberico, D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107, 174–238. (4) Oi, S.; Funayama, R.; Hattori, T.; Inoue, Y. Tetrahedron 2008, 64, 6051–6059. Ackermann, L. Org. Lett. 2005, 7, 3123–3125. Ackermann, L.; Althammer, A.; Born, R. Angew. Chem., Int. Ed. 2006, 45, 2619–2622. Ackermann, L.; Born, R.; Alvarez-Bercedo, P. Angew. Chem., Int. Ed. 2007, 46, 6364–6367. (d) Ackermann, L.; Althammer, A.; Born, R. Tetrahedron 2008, 64, 6115–6124. (e) Oi, S.; Sato, H.; Sugawara, S.; Inoue, Y. Org. Lett. 2008, 10, 1823–1826. (5) Ozdemir, I.; Demir, S.; Cetinkaya, B.; Gourlaouen, C.; Maseras, F.; Bruneau, C.; Dixneuf, P. H. J. Am. Chem. Soc. 2008, 130, 1156–1157. Ackermann, L.; Vicente, R.; x.; Althammer, A. Org. Lett. 2008, 10, 2299– 2302. (6) Matsuura, Y.; Tamura, M.; Kochi, T.; Sato, M.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007, 129, 9858–9859. (7) Davies, D. L.; Al-Duaij, O.; Fawcett, J.; Giardiello, M.; Hilton, S. T.; Russell, D. R. Dalton Trans. 2003, 4132–4138.

with Macgregor we have investigated the mechanism of this reaction8 and related acetate-assisted cyclometalations9,10 using DFT calculations. These studies have shown that the CsH activation step involves a simultaneous activation of the CsH bond by the metal and intramolecular deprotonation by acetate. This type of mechanism has been proposed for several catalytic cycles with palladium,11,12 platinum,13 and indeed ruthenium,5 and Fagnou has used the term concerted metalation-deprotonation (CMD) to describe this mechanism.12 We now wish to report experimental observations on cyclometalation of 2-substituted pyridines, which provide further support for the intramolecular nature of the deprotonation and which highlight some of the issues involved in extending these processes from activation of sp2 CsH bonds to sp3 CsH bonds.

Results and Discussion Reactions of 2-phenylpyridine with [MCl2Cp*]2 (M ) Ir, Rh) and [RuCl2(p-cymene)]2 in the presence of sodium acetate occur at room temperature to yield the complexes [MCl(L1)(ring)] 1a-c in good yields. During the course of our work Pfeffer et (8) Davies, D. L.; Donald, S. M. A.; Al-Duaij, O.; Macgregor, S. A.; Polleth, M. J. Am. Chem. Soc. 2006, 128, 4210–4211. (9) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc. 2005, 127, 13754–55. (10) Davies, D. L.; Donald, S. M. A.; Al-Duaij, O.; Fawcett, J.; Little, C.; Macgregor, S. A. Organometallics 2006, 25, 5976–5978. (11) Garcia-Cuadrado, D.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 1066–1067. Garcia-Cuadrado, D.; deMendoza, P.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2007, 129, 6880–6886. Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754–8756. (12) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848–10849. (13) Ziatdinov, V. R.; Oxgaard, J.; Mironov, O. A.; Young, K. J. H.; Goddard, W. A.; Periana, R. A. J. Am. Chem. Soc. 2006, 128, 7404–7405.

10.1021/om800909w CCC: $40.75  2009 American Chemical Society Publication on Web 12/19/2008

434 Organometallics, Vol. 28, No. 2, 2009

Boutadla et al. Scheme 1. Reaction of 2-Acetylpyridine with [RhCl2Cp*]2 in the Presence of NaOAc

Figure 1. Ortep plot of 1a. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Ir(1)sN(1), 2.074(5), Ir(1)sC(11), 2.058(5); Ir(1)sCl(1), 2.4046(15); C(11)s Ir(1)sN(1), 78.0(2); Ir(1)sC(11)sC(6), 116.2(4); Ir(1)sN(1)sC(5), 116.5(4); C(6)sC(5)sN(1), 113.8(5); C(5)sC(6)sC(11), 115.1(5).

Figure 2. Ortep plot of 1b. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Rh(1)sN(1), 2.099(3), Rh(1)sC(11), 2.035(3); Rh(1)sCl(1), 2.392(1); C(11)s Rh(1)sN(1), 78.7(1); Rh(1)sC(11)sC(6), 115.7(2); Rh(1)s N(1)sC(5),115.8(2);C(6)sC(5)sN(1),114.2(3);C(5)sC(6)sC(11), 115.5(3).

al. reported14 that this method works for cyclometalation of 2-phenylpyridine with [MCl2Cp*]2 (M ) Rh, Ir), while ruthenium complex 1c has been prepared previously by the same workers by transmetalation with [L1HgCl].15 The characterization of complexes 1a-c is in accord with previously published data. The structure of the ruthenium complex has been published;15 however for rhodium and iridium the only structures are of complexes that have a Cr(CO)3 unit π-coordinated to the cyclometalated phenyl.14 Hence, we have determined the structures of the rhodium and iridium complexes 1a and 1b, and these are shown in Figures 1 and 2, respectively, with selected distances and angles. The chelate bite angle of the cyclometalated ligand is 78.0(2)° and 78.71(12)° in 1a and 1b, respectively. The MsN bond in 1a and 1b [2.074(2) and 2.099(2) Å, respectively] is longer than the MsC(phenyl) bond (14) Scheeren, C.; Maasarani, F.; Hijazi, A.; Djukic, J. P.; Pfeffer, M.; Zaric, S. D.; Le Goff, X. F.; Ricard, L. Organometallics 2007, 26, 3336– 3345. (15) Djukic, J. P.; Berger, A.; Duquenne, M.; Pfeffer, M.; de Cian, A.; Kyritsakas-Gruber, N. Organometallics 2004, 23, 5757–5767.

[2.058(5) and 2.035(3) Å, respectively]. These bond lengths are reasonably similar to the corresponding Cr(CO)3 complexes reported earlier.14 However a notable difference with the Cr(CO)3 complexes is the planarity of the phenylpyridine ligand. The dihedral angle between the phenyl and pyridine rings, C(11)sC(6)sC(5)sN(1), is 5.47° and 2.95° in 1a and 1b, respectively, which are much smaller than those, 12.86° and 9.72°, observed for the corresponding Cr(CO)3 complexes, consistent with the large steric effect of the bulky Cr(CO)3 unit as noted previously.14 Having demonstrated that pyridine could act as a directing group for metalation of a phenyl sp2 CsH bond in these complexes, we decided to test whether it could also promote activation of an sp3 CsH bond. To our knowledge there are only two previous examples of cyclometalation of sp3 CsH bonds with these half-sandwich dimers, both with [IrCl2Cp*]2.16,17 Our attempts to cyclometalate 2-ethylpyridine with [MCl2Cp*]2 (M ) Ir, Rh) in the presence of sodium acetate failed, the dimers just reacting with acetate, as we have observed previously.7 Our mechanistic studies8-10 have shown that hydrogen bonding between the CsH bond and acetate is key to the process; hence we decided to test 2-acetylpyridine as a substrate since this has a similar structure, but the methyl CsH bonds will be more acidic, hence more favorable for hydrogen bonding. Reaction of 2-acetylpyridine (HL2) with [IrCl2Cp*]2 in the presence of sodium acetate was monitored by ES mass spectrometry, and after 4 h all the ligand had reacted. Several iridium-containing species were observed, including ions at m/z 569 [Cp*Ir(L2)(HL2)] and 448 [Cp*Ir(L2)], suggesting that cyclometalation had occurred. The 1H NMR spectrum of the crude product showed the presence of more than two Cp*Ir species and several signals for pyridine protons. Unfortunately it was not possible to isolate any pure products even after attempted chromatography. However, two mutually coupled doublets were observed at δ 2.96 and 3.40, which are consistent with a CsH activation product (see below). It is possible that 2a is formed and then reacts further with 2-acetylpyridine. Pfeffer et al. have previously reported difficulty in isolating CsH activation products of primary benzylamines due to fast reaction of the initially formed product with unreacted amine.18 The corresponding reaction with [RhCl2Cp*]2 gave 2b in good yield (Scheme 1). The 1H NMR spectrum of 2b showed a signal at δ 1.57 due to the Cp* and four multiplets in the aromatic region, each integrating to 1H due to the pyridine ring. However, there was no methyl signal; instead two mutually coupled doublets of doublets were observed at δ 2.84 (J ) 7, 1 Hz) and 3.84 (J ) 7, 1 Hz) (the smaller coupling is to Rh), assigned to a metal-bound CH2. These resonances confirm the expected sp3 CsH activation, and their inequivalence shows that epimerization at the metal is slow on the NMR time scale. In the 13C{1H} (16) Bauer, W.; Prem, M.; Polborn, K.; Sunkel, K.; Steglich, W.; Beck, W. Eur. J. Inorg. Chem. 1998, 485–493. (17) Wik, B. J.; Romming, C.; Tilset, M. J. Mol. Catal. A: Chem. 2002, 189, 23–32. (18) Sortais, J. B.; Pannetier, N.; Holuigue, A.; Barloy, L.; Sirlin, C.; Pfeffer, M.; Kyritsakas, N. Organometallics 2007, 26, 1856–1867.

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Organometallics, Vol. 28, No. 2, 2009 435 Scheme 2. Reaction of 2-Acetylpyridine and [IrCl2Cp*]2 or [RuCl2(p-cymene)]2

Figure 3. Ortep plot of 2b. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Rh(1)sN(1), 2.112(2), Rh(1)sC(1), 2.138(3); Rh(1)sCl(1), 2.4294(8); O(1)sC(2), 1.224(4); C(1)sRh(1)sN(1), 77.8(1); Rh(1)sC(1)sC(2), 101.1(2); Rh(1)sN(1)sC(3),112.2(2);C(2)sC(3)sN(1),113.0(3);C(1)sC(2)sC(3), 112.7(3).

NMR spectrum, the CH2 carbon was observed at δ 45.33 as a doublet (JRhC 22 Hz). The FAB mass spectrum of 2b showed an ion at m/z 393 due to [M]+ and a fragment ion at m/z 358 due to [M - Cl]+. Crystals of 2b suitable for X-ray diffraction were obtained from dichloromethane/hexane, and the structure is discussed below. The structure of 2b is shown in Figure 3, with selected bond distances and angles, and this confirms the activation of an sp3 CsH bond of a methyl group. Complex 2b has a pseudooctahedral geometry about the metal. The RhsN bond length [2.112(2) Å] is similar to that [2.099(2) Å] in 1b (Vide supra); however, the RhsC(1) bond length [2.138(3) Å] in 2b is significantly longer than the RhsC(phenyl) bond [2.035(3) Å] in 1b (see above), consistent with a bond to an sp3 carbon rather than an sp2 one. Indeed, the RhsC(1) bond length is similar to the IrsCH2 bond length [2.165(3) Å] in a Cp* iridium cyclometalated diimine.17 The CsO bond length is 1.224(4) Å, as expected for a double bond. The presence of the sp3hybridized carbon has a marked effect on the bond angles and conformation of the metallacycle. Thus, the 2-acetylpyridine ligand has a chelate angle of 77.84(11)°, similar to that (78.71(12)°) in 1b, but the angle at the sp3 carbon C(1) (RhsC(1)sC(2) 101.1(2)°) is considerably smaller than 115.7(2)° at the sp2 carbon in 1b, with the other angles in the metallacycle (average 112.6°) being slightly reduced from those in 1b (average 115.2°). As a result, the pyridine and acetyl groups are significantly nonplanar; the dihedral angle C(1)sC(2)sC(3)s N(1) is 26.65°. As found for other cyclometalated Cp* complexes,7,14 2b shows an η-Cp* coordination with three short RhsC bonds [2.141(3)-2.160(3) Å] and two longer ones [2.222(3)-2.231(3) Å]. The reaction of 2-acetylpyridine and [RuCl2(p-cymene)]2 in the presence of NaOAc, as in the case with iridium, failed to give any pure products, though all the ruthenium complex did react. Hence, in the case of acetylpyridine it seems that sp3 CsH activation is more successful with rhodium than iridium, or ruthenium. This contrasts with our previous synthetic work for phenyl CsH bond activation, in which CsH activation was superior with iridium.7 The reason for this difference may not be related to the CsH activation step. Indeed DFT calculations suggest there is very little difference in activation barrier for acetate-assisted CsH activation with these three metals.19 To investigate this difference further, we examined the interaction

of 2-acetylpyridine with the dimers [MCl2Cp*]2 (M ) Rh, Ir) and [RuCl2(p-cymene)]2 in the absence of acetate. The coordination of 2-acetylpyridine to [MCl2Cp*]2 (M ) Ir, Rh) and [RuCl2(p-cymene)]2 was examined by 1H NMR spectroscopy at different temperatures (Scheme 2). In the case of [RhCl2Cp*]2, no coordination of 2-acetylpyridine was observed, even at low temperature (247 K). It is interesting to note that for rhodium even the simple pyridine adduct [RhCl2(C5H5N)Cp*] was reported as being unstable in solution in the absence of free pyridine.20 In the case of iridium the 1H NMR spectrum of a mixture of [IrCl2Cp*]2 and 2-acetylpyridine (1:2 molar ratio) in CD2Cl2 at 300 K showed mainly the presence of both starting materials but with two additional broad signals at δ 1.75 and 3.26 due to a Cp* and an acetyl methyl with some very weak multiplets in the pyridine region. This new species integrated to about 5% of the starting materials and was assigned to the N,O chelate complex salt 4a, rather than a simple N-coordinated neutral adduct 3, in equilibrium with starting materials (Scheme 2). As the temperature was lowered, the aromatic pyridine signals of 4a became well resolved, giving two doublets at δ 8.96 and 9.13 and two triplets at δ 8.66 and 8.13. These were assigned to H6, H3, H4, and H5, respectively, on the basis of ROESY experiments at 270 K, which show correlations between signals for free and coordinated 2-acetylpyridine. The proportion of coordinated 2-acetylpyridine increased as the temperature was lowered, and at 211 K the equilibrium was slow on the NMR time scale and coordinated and free 2-acetylpyridine were present in approximately a 1:1 ratio. Notably, all the signals of the 2-acetylpyridine shifted downfield on coordination, the largest coordination shift (1.04 ppm) being observed for H3 (see below). Further information on the structure of the complex in solution is available from observation of NOEs between H6 and the Cp*, and between H3 and the acetyl methyl, suggesting that the carbonyl oxygen is pointing in the same direction as the nitrogen, i.e., toward the metal. Interestingly addition of d4-methanol to the NMR sample (20% by volume) caused a significant shift of the equilibrium position, favoring coordinated 2-acetylpyridine over free 2-acetylpyridine (ratio 3:1 at room temperature), and also slowed the exchange between free and coordinated 2-acetylpyridine. This result suggests the new complex is 4a rather than 3 since the presence of methanol is likely to have a more significant effect on the stability of the salt than on the neutral species. It seems that in CD2Cl2 formation of 4a is not very favorable due to the formation of chloride anion. Addition of methanol provides better solvation of the chloride and hence displaces the equilibrium toward 4a. Hence, the large coordination shift (see above) for (H3) may be due to hydrogen bonding with the chloride anion, which is in close contact in CD2Cl2. The reaction of [RuCl2(p-cymene)]2 and 2-acetylpyridine (1:2 molar ratio) was also carried out in CD2Cl2 in an NMR tube. (19) Poblador-Bahamonde, A. ; Davies, D. L.; Donald, S. M. A.; Macgregor, S. A., unpublished results. (20) Kang, J. W.; Moseley, K.; Maitlis, P. M. J. Am. Chem. Soc. 1969, 91, 5970.

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After 10 min the 1H NMR spectrum showed the presence of two new ruthenium species as well as some starting materials. The major new ruthenium species (30%) showed four broad multiplets at δ 9.65, 8.24, 8.14, and 8.08 for the pyridine protons, four multiplets between δ 5.9 and δ 6.22 for the p-cymene group, and signals due to acetyl and isopropyl protons. The high frequency of the p-cymene aromatic protons is consistent with a cationic species, and their inequivalence agrees with a chiral metal center; therefore we assign these to the N,O chelate complex 4c. The other new species present had signals due to a Ru(p-cymene) fragment but with no additional pyridine signals. These signals have been assigned to the anionic species [RuCl3(p-cymene)]-, which is formed from the chloride liberated in the formation of the N,O chelate cation. The amount of [RuCl3(p-cymene)]- did not match that of the cation of 4c; hence there was still some free chloride. Note, the complex Cs[RuCl3(benzene)] has been reported previously though it was not fully characterized.21 We have independently prepared [RuCl3(p-cymene)]- by the addition of Et4NCl to [RuCl2(pcymene)]2 and confirmed the identity of the anion by electrospray mass spectrometry (m/z 343 in CH2Cl2), and have shown that the anion and dimer interconvert on the NMR time scale. As in the case of iridium, variable-temperature NMR spectroscopy and ROESY spectra indicated that free and coordinated 2-acetylpyridine were exchanging on the NMR time scale, and hence 4c is exchanging with [RuCl2(p-cymene)]2 and [RuCl3(pcymene)]-. As the temperature was lowered, the proportion of 4c increased to 40% at 258 K. The addition of only 10 molar equiv (per ruthenium) of d4-methanol was sufficient to displace the equilibrium still further to approximately 1:1 (coordinated: free 2-acetylpyridine) at room temperature. In order to more fully characterize the N,O chelates and investigate whether they are on the pathway to CsH activation, we attempted to isolate these species as the PF6 salts. Reactions of 2-acetylpyridine (HL2) with [MCl2Cp*]2 (M ) Ir, Rh) and [RuCl2(arene)]2 (arene ) p-cymene, mesitylene) were carried out in dichloromethane in the presence of KPF6. In the case of iridium the N,O chelate complex [IrCl{C5H4N2-C(dO)CH3-KN,O}Cp*]PF6 (4a) was isolated in 74% yield. The 1H NMR spectrum of 4a showed two singlets at δ 3.10 and 1.79 due to the methyl group and Cp*, respectively. The pyridine protons gave rise to three doublets of doublets of doublets at δ 8.91 (H6), 8.50 (H3), and 8.05 (H5) and a doublet of triplets at δ 8.34 (H4). Thus, in this case with PF6 as the anion H3 is more upfield than in the chloride case, reflecting the lack of hydrogen bonding to the anion. The 13C NMR spectrum showed the expected number of carbons, the CO was observed at δ 210.78, and a peak at δ 26.04 was assigned to the acetyl methyl group. The FAB mass spectrum showed ions at m/z 484 due to the cation [IrCl(HL2)Cp*]+. Crystals of this compound were obtained from DCM/hexane and were suitable for X-ray diffraction, and the structure is discussed with a ruthenium analogue below. An attempt to make the corresponding compound with [RhCl2Cp*]2 under the same conditions failed. The 1H NMR spectrum showed the free ligand and [RhCl2Cp*]2 were still present. The same reaction was attempted with [RuCl2(p-cymene)]2 and [RuCl2(mes)]2. The latter was chosen as a starting material since it has much simpler 1H NMR signals than [RuCl2(pcymene)]2, which makes identification much easier. Reaction of 2-acetylpyridine with [RuCl2(p-cymene)]2 in the presence of KPF6 gave 4c in 58% yield. The 1H NMR spectrum was very (21) Robertson, D. R.; Stephenson, T. A.; Arthur, T. J. Organomet. Chem. 1978, 162, 121–136.

Boutadla et al.

Figure 4. Ortep plot of 4a. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Ir(1)sN(1), 2.101(11), Ir(1)sO(1), 2.154(10); Ir(1)sCl(1), 2.377(5); O(1)sC(6), 1.235(17); O(1)sIr(1)sN(1), 76.1(4); Ir(1)sO(1)sC(6), 117.0(9); Ir(1)sN(1)sC(1), 114.8(8); C(6)sC(1)sN(1), 113.8(12); C(1)s C(6)sO(1), 117.5(13).

Figure 5. Ortep plot of 4d. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Ru(1)sN(1), 2.106(4), Ru(1)sO(1), 2.105(3); Ru(1)sCl(1), 2.385(1); O(1)sC(6), 1.234(5); O(1)sRu(1)sN(1), 75.92(13); Ru(1)sO(1)sC(6), 117.8(3); Ru(1)sN(1)sC(1), 114.9(3); C(6)sC(1)sN(1), 114.0(4); C(1)s C(6)sO(1), 117.3(4).

similar to the spectrum observed in the NMR reaction described previously with minor changes in chemical shifts for some of the pyridine protons presumably due to different interactions with the PF6 anion rather than chloride, and full details of the characterization are given in the Experimental Section. Reaction of 2-acetylpyridine with [RuCl2(mes)]2 and KPF6 gave 4d in 87% yield. The 1H NMR spectrum was similar to 4a,c, with four signals in the aromatic region due to the pyridine. The most downfield was a doublet at δ 9.21 assigned to H6. A singlet for the methyl group was observed at δ 3.01 and two singlets for the mesitylene, one for the methyl groups at δ 2.33 (9H) and one for the aromatic CH at δ 5.37 (3H). The 13C NMR spectrum showed the expected number of carbons, and the acetyl methyl was seen at δ 25.8. The FAB mass spectrum showed ions at m/z 378 due to [M]+. Crystals of this compound were obtained from DCM/hexane and were suitable for X-ray diffraction. The structures of 4a and 4d with selected bond distances and angles are shown in Figures 4 and 5, respectively. The RusN and RusO bond lengths, 2.106(4) and 2.105(3) Å, respectively, are identical in 4d, but the IrsO, 2.154(10) Å, is slightly longer

Acetate-Assisted C-H ActiVation

than the IrsN, 2.101(11) Å, in 4a. The OsMsN chelate angles are the same (ca. 76°) in both complexes. The other angles in the metallacyclic rings are all between 117.8° and 113.8°, and the acetylpyridine is almost planar in both complexes. The NsC-CsO torsion angle is less than 4° in both complexes. An important consideration in the reactivity of these complexes is whether the acetyl protons are acidic. We noticed that over time the signals due to the acetyl methyl protons in the 1H NMR spectra of 4a and 4d (in d4-methanol) gradually disappeared though the other signals were unchanged. This disappearance was accelerated by the addition of D2O, and we assign it to deuterium incorporation via a ket-enol equilibrium and proton exchange with D2O in the NMR solvent. The amount of enol complex present is presumably very small, as no signals for this species were observed. In an attempt to isolate the enol complex and to assess whether these N,O chelate complexes can be intermediates on the way to CsH-activated N,C complexes, we have attempted deprotonation of the complexes. Complexes 4a and 4d were each treated with NaOAc in dichloromethane; however, no reaction occurred in either case. The 1H NMR spectra showed only the starting compounds after 4 h. Note the reaction of [RhCl2Cp*]2 with 2-acetylpyridine and NaOAc has progressed significantly within this time, suggesting that complexes 4 are not intermediates en route to complexes 2. We have also tested the reaction of 4d with a stronger base. Thus, 4d was reacted with sodium methoxide. The 1H NMR spectrum showed that a reaction occurred with no starting material remaining; two different sets of mesitylene signals, in a 1:1 ratio, were observed, indicating a possible unsymmetrical dimer with additional signals at δ 1.96 due to a methyl and two single proton signals at δ 3.19 and 6.54, the former of which is assigned as a hydroxyl proton since it exchanges with D2O. Unfortunately we have not managed to get the compound totally pure; it transforms to further products if left in solution for long periods. However, we have managed to get some crystals from the product, and the structure with selected bond distances and angles is shown in Figure 6. The structure shows an unsymmetrical dicationic dimer 5. Each ruthenium is coordinated to an η6 mesitylene ring and there is a bridging chloride. The coordination of Ru(1) is completed by an N,O chelated acetylpyridine, the original methyl group of which, C(7), has been deprotonated twice and is bonded to C(8) and Ru(2). There is some contribution from an enol resonance form for C(7)sC(6)sO(1) in the 2-acetylpyridine bonded to Ru(1). Thus, C(7)sC(6) (1.385(14) Å) and Ru(1)sO(1) (1.995(9) Å) are somewhat shorter, and O(1)sC(6) (1.286(12) Å) somewhat longer than the corresponding bonds, 1.481(6), 2.105(3), and 1.234(5) Å, respectively, in the N,O chelate complex 4d. It would appear that deprotonation of 4d leads to a very reactive O-bound enolate, which immediately reacts in an aldol-type reaction with the cationic starting material rather than isomerize to an N,C-bound enolate. The deuterium incorporation results and formation of complex 5 shows that deprotonation of complexes 4 can occur; however the enolate formed is clearly very reactive. The failure of OAc to convert the cationic NsO chelate 4a,d to NsC complexes 2a,d suggests these are not intermediates on the pathway to the cyclometalated N,C products. In a further attempt to investigate the stability of C- or O-bound enolates, we attempted the reactions of the dimers [MCl2Cp*]2 (M ) Rh, Ir) and [RuCl2(pcymene)]2 with the preformed enolate of 2-acetylpyridine (Scheme 3). The lithium enolate was made in situ by reaction of 2-acetylpyridine with LiHMDS in THF at -80 °C, and after

Organometallics, Vol. 28, No. 2, 2009 437

Figure 6. Ortep plot of 5. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Ru(1)sN(1), 2.099(10),Ru(1)sO(1),1.995(9);Ru(1)sCl(1),2.442(3);Ru(2)sN(2), 2.080(11),Ru(2)sC(7),2.203(12);Ru(2)sCl(1),2.441(3);O(1)sC(6), 1.286(12); O(2)sC(8), 1.442(13); C(6)sC(7), 1.385(14); C(7)sC(8), 1.540(15); O(1)sRu(1)sN(1), 77.4(4); Ru(1)sO(1)sC(6), 114.7(7); Ru(1)sN(1)sC(1), 113.1(8); C(6)sC(1)sN(1), 111.7(11); C(1)s C(6)sO(1), 116.1(10); C(7)sRu(2)sN(2), 75.3(4); Ru(2)sC(7)s C(6), 108.7(8); Ru(2)sN(2)sC(10), 120.3(9); C(8)sC(10)sN(2), 114.9(12); C(7)sC(8)sC(10), 109.7(11). Scheme 3. Reaction of the Lithium Enolate of 2-Acetylpyridine with [MCl2Cp*]2 (M ) Ir, Rh) or [RuCl2(p-cymene)]2

stirring for 1 h the relevant dimer was added. The reaction with [RhCl2Cp*]2 gave N,C chelate complex 2b in 81% yield with identical spectroscopic data to the sample prepared by CsH activation. Similarly, the reaction with [IrCl2Cp*]2 gave the iridium C-bound enolate 2a. The spectrum showed four signals for the pyridine group and a Cp* signal at δ 1.55. There was no methyl signal; instead two mutually coupled doublets were observed at δ 3.41 and 3.00 assigned to the metal-bound CH2. Hence, the lithium enolate gave the N,C product 2a rather than an isomeric N,O enolate complex. The inequivalence of the metal-bound CH2 resonances also shows that epimerization at the metal is slow on the NMR time scale. The ES mass spectrum showed a molecular ion at m/z 448 [M - Cl]+, a fragment at m/z 406 [M - CH2CO - Cl]+, and a peak at m/z 569 corresponding to [M - Cl + HL2]+ from the substitution of the chloride by a second 2-acetylpyridine. The complex was also characterized by X-ray diffraction, and the structure is shown in Figure 7. The structure of 2a is similar to that of 2b discussed above. The IrsN bond length [2.094(6) Å] is similar to the IrsN bond length [2.074(5)] in 1a (Vide supra); however, the IrsC(7) bond, [2.121(8) Å], in 2a is significantly longer than the IrsC(11) bond [2.058(5) Å] in 1a and is similar to the RhsC bond length [2.138(3) Å] in 2b but slightly shorter than the IrsCH2 bond length [2.165(3) Å] in a Cp*iridium cyclometalated diimine.17 As in 2b, the presence of the sp3-hybridized carbon has a marked

438 Organometallics, Vol. 28, No. 2, 2009

Figure 7. Ortep plot of 2a. Thermal ellipsoids are drawn at 50% probability level, and hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Ir(1)sN(1), 2.094(6), Ir(1)sC(7), 2.121(8); Ir(1)sCl(1), 2.424(2); O(1)sC(6), 1.213(10); C(7)sIr(1)sN(1), 77.2(3); Ir(1)sC(7)sC(6), 102.1(5); Ir(1)sN(1)sC(5),114.5(5);C(6)sC(5)sN(1),111.6(6);C(5)sC(6)sC(7), 112.2(7).

effect on the bond angles and conformation of the metallacycle. Thus, the 2-acetylpyridine ligand has a chelate angle of 77.2(3)° (cf. 77.84(11)° in 2b), but the angle at the metalated carbon [IrsC(7)sC(6)] is 102.1(5)° (cf. 101.1(2)° in 2b) and the average of the other angles in the metallacycle is 112.8°, statistically the same as in 2b. As a result, the pyridine and acetyl groups are significantly nonplanar; the dihedral angle C(7)sC(6)sC(5)sN(1) is 26.7°, the same as the corresponding angle in 2b. The reaction of the lithium enolate with [RuCl2(p-cymene)]2 was not as clean, and we have failed to isolate the product pure; however the major product could be identified as 2c from the 1 H NMR spectrum. The spectrum showed the expected signals for a coordinated p-cymene and four multiplets for the pyridine (see Experimental Section for details) and two mutually doublets at δ 3.72 and 3.08 as expected for the CH2 group bonded to the metal. The formation of the N,C chelates 2a,c is proof that these compounds are stable and can be made by an alternative route to direct CsH activation of the sp3 bond. The failure of the iridium and ruthenium dimers to give pure 2a,c by the CsH activation route is therefore not due to thermodynamic instability of the product. These results suggest that if the pyridine coordinates to the chloride dimer before reaction with acetate, then other reaction pathways are opened and acetate-assisted CsH activation may not occur. This is consistent with our mechanism in which the acetate must be coordinated to the metal in the CsH activation step. Ikariya et al. have also reported that [Ir(OAc)2Cp*] can carry out CsH activation in the absence of added acetate.22 To further investigate the mechanism, we have examined the coordination of 2-ethyl and 2-phenylpyridine with [MCl2Cp*]2 (M ) Rh, Ir) in the absence of sodium acetate by 1H NMR spectroscopy at different temperatures. The 1H NMR spectrum of 2-ethylpyridine with [IrCl2Cp*]2 shows exchange is occurring between the starting materials and a 2-ethylpyridine complex of type 3. The two Cp* signals are very broad, as are the signals for H6 and the CH2 of the ethyl group. The integration suggests that the major species is the coordinated complex. At 233 K the spectrum shows sharp (22) Arita, S.; Koike, T.; Kayaki, Y.; Ikariya, T. Organometallics 2008, 27, 2795–2802.

Boutadla et al.

signals indicating that exchange is now slow on the NMR time scale. At this point two multiplets are observed for the CH2 of the ethyl group at δ 2.96 and 3.70, showing that coordination has occurred and that these two protons are inequivalent. This proves that the plane of the pyridine is not perpendicular to the Cp* and there is no mirror plane in the molecule; that is, it is chiral. In the case of the reaction of 2-ethylpyridine with [RhCl2Cp*]2 there is no evidence for coordination at room temperature; however, at 247 K the NMR shows broad resonances corresponding to the coordinated 2-ethylpyridine (20%) although it is still exchanging on the NMR time scale. Similar reaction of 2-phenylpyridine with [IrCl2Cp*]2 gave no evidence for any coordination of the pyridine even at 247 K. In conclusion, in the case of 2-phenylpyridine the pyridine does not react until after the dimer has reacted with acetate, consistent with easy CsH activation of this substrate by [MCl2Cp*]2 (M ) Ir, Rh) and [RuCl2(p-cymene)]2. In the case of 2-ethylpyridine, even though the reaction with acetate can occur first, there is no subsequent CsH activation. We have noted previously that hydrogen bonding plays an important role in the CsH activation step.10 The decreased acidity of the proton to be activated in 2-ethylpyridine compared with 2-acetylpyridine may be a factor in the lower reactivity of 2-ethylpyridine. In addition, the need to include another sp3 carbon in the metallacyclic ring may also make cyclometalation of 2-ethylpyridine less favorable. In the case of 2-acetylpyridine with [RhCl2Cp*]2 reaction with acetate occurs first, leading to C-H activation product 2b; however, for iridium and ruthenium the possibility of forming an N,O chelate, 4a,c, provides an alternative reaction pathway that is competitive with the acetateassisted CsH activation.

Experimental Section All reactions were carried out at room temperature under nitrogen; however the workup was carried out in air unless stated otherwise. 1H, and 13C{1H} NMR spectra were obtained using a Bruker ARX 400 MHz spectrometer, with CDCl3 as solvent, unless otherwise stated. Chemical shifts were recorded in ppm (on δ scale for 1H NMR, with tetramethylsilane as internal reference), and coupling constants are reported in Hz. FAB mass spectra were obtained on a Kratos concept mass spectrometer using NOBA as matrix, and electrospray (ES) mass spectra were recorded using a micromass Quattro LC mass spectrometer in acetonitrile. Microanalyses were performed by the Elemental Analysis Service (London Metropolitan University). Starting materials [MCl2Cp*]2 (M ) Rh, Ir),23 [RuCl2(p-cymene)]2,24 and [RuCl2(mes)]224 were made by literature methods; other compounds were obtained from Aldrich and Alfa Aesar. Preparation of [MCl(C6H4-2-C5H4N-K-C,N)(ring)] (1a-c) (M ) Rh, Ir, ring ) Cp*; M ) Ru, ring ) p-cymene). A mixture of [MCl2(ring)]2, 2-phenylpyridine (2.2 equiv), and sodium acetate (2.5 equiv) in CH2Cl2 (5 mL) was stirred for 4 h at room temperature. The solution was filtered through Celite and rotary evaporated to dryness. The product was crystallized from CH2Cl2/ hexane to give 1a-c (55, 75, 61%, respectively) as orange (Ir, Rh) or brown (Ru) crystals. The spectroscopic data are consistent with the literature.14,15 Preparation of [RhCl{C5H4N-2-C(dO)CH2-KC,N}Cp*], 2b. A mixture of NaOAc (58.7 mg, 0.49 mmol), [RhCl2Cp*]2 (150 mg, 0.24 mmol), and 2-acetylpyridine (53 mg, 0.44 mmol) was stirred for 20 h at room temperature. The solution was filtered through (23) White, C.; Yates, A.; Maitlis, P. M. Inorg. Synth. 1992, 29, 228. (24) Bennett, M. A.; Smith, A. K. J. Chem. Soc., Dalton Trans. 1974, 233.

Acetate-Assisted C-H ActiVation

Organometallics, Vol. 28, No. 2, 2009 439 Table 1. Crystallographic Data for Complexes 1a,b, 2a,b, 4a,d, and 5 1a

1b

2a

2b

no. of reflns collected no. of indep collected (Rint) data/restraints/params goodness-of-fit, F2 final R indices [I > 2σ(I)]

C21H23ClIrN 517.05 150(2) monoclinic P2(1)/c 7.474(2) 14.685(4) 16.615(4) 90 97.304(5) 90 1808.8(8) 4 1.899 7.531 1000 0.13 × 0.10 × 0.07 1.86 to 26.00 -9 e h e 9, -18 e k e 18, -20 e l e 20 13 926 3555 [R(int) ) 0.0533] 3555/0/222 1.017 R1 ) 0.0322, wR2 ) 0.0579

C21H23ClNRh 427.76 150(2) monoclinic P2(1)/n 7.4528(13) 14.780(3) 16.956(3) 90 102.644(3) 90 1822.5(6) 4 1.559 1.085 872 0.15 × 0.12 × 0.07 1.85 to 26.00 -9 e h e 9, -18 e k e 18, -20 e l e 20 14 041 3580 [R(int) ) 0.0458] 3580/0/222 1.004 R1 ) 0.0349, wR2 ) 0.0708

C17H21ClIrNO 483.00 150(2) orthorhombic Iba2 14.227(3) 16.654(3) 13.727(3) 90 90 90 3252.3(11) 8 1.973 8.373 1856 0.21 × 0.11 × 0.03 1.88 to 26.00 -17 e h e 17, -20 e k e 20, -16 e l e 16 12 174 3162 [R(int) ) 0.0621] 3162/1/195 0.994 R1 ) 0.0327, wR2 ) 0.0713

R indices (all data)

R1 ) 0.0431, wR2 ) 0.0604

R1 ) 0.0465, wR2 ) 0.0741

R1 ) 0.0385, wR2 ) 0.0730

largest diff. peak and hole/e Å-3

1.220 and -1.001

0.819 and -0.504

2.316 and -1.111

C17H21ClNORh 393.71 293(2) orthorhombic Iba2 14.512(2) 16.715(2) 13.660(2) 90 90 90 3313.5(9) 8 1.578 1.190 1600 0.32 × 0.21 × 0.08 mm3 1.86 to 26.00 -17 e h e 17, -20 e k e 20, -16 e l e 16 12 205 3243 [R(int) ) 0.0292] 3243/1/195 1.090 R1 ) 0.0246, wR2 ) 0.0587 R1 ) 0.0255, wR2 ) 0.0592 1.292 and -0.263

empirical formula fw temp/K cryst syst space group a/Å b/Å c/Å R/deg β/deg γ/deg U/Å3 Z density(calc)/Mg m-3 abs coeff/mm-1 F(000) cryst size/mm θ range/deg index ranges

empirical formula fw temp/K cryst syst space group a/Å b/Å c/Å R/deg β/deg γ/deg U/Å3 Z density(calc)/Mg m-3 abs coeff/mm-1 F(000) cryst size/mm θ range/deg index ranges no. of reflns collected no. of indep collected (Rint) data/restraints/params goodness-of-fit, F2 final R indices [I > 2σ(I)] R indices (all data) largest diff peak and hole/e Å-3

4a

4d

7

C18H23Cl4F6IrNOP 748.34 150(2) monoclinic P2(1)/c 11.915(13) 13.452(15) 16.428(18) 90 106.67(2) 90 2522(5) 4 1.971 5.837 1440 0.17 × 0.12 × 0.08 1.78 to 26.00 -14 e h e 14, -16 e k e 16, -19 e l e 20 19 294 4959 [R(int) ) 0.1745] 4959/0/268 0.934 R1 ) 0.0857, wR2 ) 0.1976 R1 ) 0.1159, wR2 ) 0.2096 5.542 and -4.648

C16H19ClF6NOPRu 522.81 150(2) monoclinic C2/c 29.187(4) 9.8982(13) 15.325(2) 90 120.985(2) 90 3795.6(9) 8 1.830 1.114 2080 0.15 × 0.10 × 0.06 1.63 to 26.00 -35 e h e 35, -12 e k e 12, -18 e l e 18 14 542 3733 [R(int) ) 0.0715] 3733/0/248 0.919 R1 ) 0.0444, wR2 ) 0.0860 R1 ) 0.0677, wR2 ) 0.0922 0.894 and -0.543

C33H39Cl3F12N2O2P2Ru2 1094.09 150(2) triclinic P1j 8.767(6) 11.659(8) 20.804(13) 92.606(15) 100.426(15) 107.533(15) 1983(2) 2 1.832 1.136 1088 0.22 × 0.08 × 0.02 1.84 to 26.00 -10 e h e 10, -14 e k e 14, -25 e l e 25 15 719 7700 [R(int) ) 0.1649] 7700/0/513 0.860 R1 ) 0.0898, wR2 ) 0.1557 R1 ) 0.2097, wR2 ) 0.1949 2.170 and -0.975

Celite and rotary evaporated to dryness to give a red solid, which was washed with hexane and diethyl ether to give 2b (150 mg, 78%). Anal. Calc for C17H21ClNORh: C, 51.86, H, 5.38, N, 3.56. Found: C, 51.82, H, 5.21, N, 3.46. 1H NMR (300 MHz): δ 1.57 (s, 15H, Cp*), 2.84 (dd, 1H, J 7, 1, CHH‘), 3.84 (dd, 1H, J 7, 1, CHH‘), 7.49 (m, 1H, H5), 7.65 (m, 1H, H3), 7.89 (dt, 1H, J 7.5, 1.5, H4), 8.65 (m, 1H, H6). 13C NMR: δ 8.82 (C5Me5), 45.33 (d, JRhC 22, CH2), 94.36 (d, JRhC 7, C5Me5), 121.44, 127.44, 138.89, 151.49 (C3, C4, C5, C6), 159.15 (C2), 197.64 (CO). MS (FAB): m/z 393 [M]+, 358 [M - Cl]+. Preparation of [IrCl{C5H4N-2-C(dO)CH3-KN,O}Cp*]PF6 (4a). A mixture of KPF6 (92 mg, 0.50 mmol), [IrCl2Cp*]2 (100 mg, 0.13 mmol), and 2-acetylpyridine (30 mg, 0.25 mmol) in CH2Cl2 (10 mL) was stirred for 4 h at room temperature. The solution was filtered through Celite and rotary evaporated to dryness.

The product was crystallized from chloroform to give 4a (117 mg, 74%) as orange crystals. Anal. Calc for C17H22ClF6NOPIr: C, 32.46, H, 3.53, N, 2.23. Found: C, 32.47, H, 3.43, N, 2.35. 1H NMR (CD2Cl2, 400 MHz): δ 1.79 (s, 15H, C5Me5), 4.00 (s, 3H, COMe), 8.05 (ddd, 1H, J 8.0, 5.5, 1.5, H5), 8.34 (td, 1H, J 8.0, 1.5, H4), 8.50 (ddd, 1H, J 8.0, 2.0, 1.5, H3), 8.91 (ddd, 1H, J 5.5, 1.5, 1.0, H6). 13C NMR: δ 8.75 (C5Me5), 26.04 (COMe), 88.80 (C5Me5), 131.43 (C3), 133.17 (C5), 140.90 (C4), 151.27 (C6), 152.19 (C2), 210.78 (CO). MS (FAB): m/z 484 [M]+. [RuCl{C5H4N-2-C(dO)CH3-KN,O}(p-cymene)]PF6 (4c). A mixture of KPF6 (60 mg, 0.33 mmol), [RuCl2(p-cymene)]2 (50 mg, 0.08 mmol), and 2-acetylpyridine (19.8 mg, 0.16 mmol) in CH2Cl2 (5 mL) was stirred for 20 h at room temperature. The solution was filtered through Celite and rotary evaporated to dryness. The product was crystallized from chloroform to give 4c (51 mg, 58%) as brown

440 Organometallics, Vol. 28, No. 2, 2009 crystals. Anal. Calc for C17H21ClF6NOPRu: C, 38.03, H, 3.94, N, 2.61. Found: C, 37.94, H, 3.85, N, 2.60. 1H NMR: δ 1.38 (d, 3H, J 7, CHMeMe’), 1.40 (d, 3H, J 7, CHMeMe’), 2.31 (s, 3H, Me), 2.95 (s, 3H, COMe), 2.99 (sept, 1H, J 7, CHMeMe’), 5.76 (d, 1H, J 6, Cy), 5.82 (d, 1H, J 6, Cy), 5.89 (d, 1H, J 6, Cy), 6.00 (d, 1H, J 6, Cy), 7.87 (ddd, 1H, J 7, 5, 1, H5), 8.18 (td, 1H, J 7, 1, H4), 8.25 (d, 1H, J 7, H3), 9.25 (d, 1H, J 5, H6). 13C NMR: δ 18.30 (Me (Cy)), 22.07, (CHMeMe’(Cy)) 22.51 (CHMeMe’(Cy)), 25.85 (COMe), 31.28 (CHMeMe’), 82.45, 83.29, 83.39, 85.47 (4 × CH, C6H4, (Cy)), 99.61 (C (C6H4)), 103.98 (C (C6H4)), 130.63 (C3), 132.07 (C5), 140.41 (C4), 151.7 (C2), 154.77 (C6), 211.24 (CO). MS (FAB): m/z 392 [M - PF6]+. [RuCl{C5H4N-2-C(dO)CH3-KN,O}(mes)]PF6 (4d). A mixture of KPF6 (63.2 mg, 0.34 mmol), [RuCl2(Mes)]2 (50 mg, 0.08 mmol), and 2-acetylpyridine (20.8 mg, 0.17 mmol) in CH2Cl2 (5 mL) was stirred for 20 h at room temperature. The solution was filtered through Celite and rotary evaporated to dryness. The product was crystallized from chloroform to give 4d (78 mg, 87%) as brown crystals. Anal. Calc for C16H19ClF6NOPRu: C, 36.76, H, 3.66, N, 2.68. Found: C, 36.86, H, 3.51, N, 2.66. 1H NMR (CD2Cl2): δ 2.33 (s, 9H, C6H3Me3), 3.01 (s, 3H, COMe), 5.37 (s, 3H, C6H3Me3), 7.94 (ddd, 1H, J 7.5, 5.5, 2, H5), 8.26 (ddd, 1H, J 8, 7.5, 1, H4), 8.30 (d, 1H, J 8, H3), 9.21 (d, 1H, J 5.5, H6). 13C NMR: δ 18.7 (C6H3Me3), 25.8 (COMe), 77.0 [CH(C6H3Me3)], 105.9 [CMe(C6H3Me3)], 130.1 (C4), 131.7 (C5), 140.2 (C3), 151.7 (C2), 154.1 (C6), 211.0 (CO). MS (FAB): m/z 378 [M]+. Reaction of [RuCl{C5H4N-2-C(dO)CH3-KN,O}(mes)]PF6 (4d) with NaOMe. NaOMe (4.1 mg, 0.076 mmol) was added to a solution of complex 4d (40 mg, 0.076 mmol) in CH2Cl2 (5 mL), and the mixture was stirred for 6 days at room temperature. Another equivalent of MeONa (4.14 mg, 0.076 mmol) was added, and the reaction was stirred for a further day. The mixture was filtered through Celite and rotary evaporated to dryness. Attempted crystallization from CH2Cl2/hexane gave a black precipitate (25 mg) and a few crystals suitable for X-ray analysis. The 1H NMR spectrum of the crystals was slightly impure, but the peaks for 5 could be assigned as follows. 1H NMR (CD2Cl2): δ 1.96 (s, 3H, MeC(OH)), 1.98 (s, 9H, C6H3Me3), 2.01 (s, 9H, C6H3Me3), 3.19 (s, 1 H, OH), 5.05 (s, 3H, C6H3Me3), 5.10 (s, 3H, C6H3Me3), 6.54 (s, 1 H, CHC(OH)), 7.47 (d, 1 H, J 7.5, Hpyr), 7.62 (dd, 1 H, J 6.0 Hpyr), 7.68 (dd, 1 H, J 5.5, Hpyr), 8.00 (t, 1 H, J 7.5, Hpyr), 8.05 (d, 1 H, J 7.5, Hpyr), 8.11 (t, 1H, J 7.5, Hpyr), 8.66 (d, 1 H, J 5.5, Hpyr), 9.01 (d, 1 H, J 5.5, Hpyr). MS (FAB): m/z 719 [M - H]+. Reaction of the Lithium Enolate of 2-Acetylpyridine with [IrCl2Cp*]2. 2-Acetylpyridine (21.3 mg, 0.176 mmol) was added to a solution of LiHMDS (0.18 mL, 0.194 mmol) in THF (5 mL) at -78 °C. After being stirred for 1 h at the same temperature, [IrCl2(Cp*)]2 (70 mg, 0.088 mmol) was added to the mixture. The mixture was allowed to warm and was stirred for 4 h. The solution was filtered through Celite and evaporated to dryness. The product, 2a, was isolated as an orange precipitate (58 mg, 68%). Anal. Calc for C17H21NOClIr: C, 42.27, H, 4.38, N, 2.90. Found: C, 42.23, H, 4.28, N, 2.81. 1H NMR (CD2Cl2, 300 MHz): δ 1.53 (s, 15H, C5Me5), 2.96 (d, 1H, J 9.5, H8), 3.40 (d, 1H, J 9.5, H8), 7.36 (ddd, 1H, J 8.0, 5.5, 1.5, H5), 7.54 (ddd, 1H, J 8.0, 1.5,1.0, H3), 7.86 (td, 1H, J 8.0, 1.5, H4), 8.51 (ddd, 1H, J 5.5, 1.5, 1.0, H6). 13C NMR: δ 7.51 (C5Me5), 35.24 (CH2), 85.56 (C5Me5), 120.47 (C3), 126.79 (C5), 137.47 (C4), 150.83 (C6), 156.54 (C2), 200.65 (CO). MS (FAB): m/z 483 [M]+, 448 [M - Cl]+. Reaction of the Lithium Enolate of 2-Acetylpyridine with [RhCl2(Cp*)]2. 2-Acetylpyridine (27.0 mg, 0.230 mmol) was added to a solution of LiHMDS (0.23 mL, 0.250 mmol) in THF (5 mL)

Boutadla et al. at -78 °C. After being stirred for 1 h at the same temperature, [RhCl2(Cp*)]2 (70 mg, 0.110 mmol) was added to the mixture. The mixture was allowed to warm and stirred for 4 h. The solution was filtered through Celite and evaporated to dryness. Complex 2b was isolated as an orange precipitate (70 mg, 81%) and was spectroscopically identical to the sample prepared by C-H activation (see above). Reaction of the Lithium Enolate of 2-Acetylpyridine with [RuCl2(p-cymene)]2. 2-Acetylpyridine (27.8 mg, 0.228 mmol) was added to a solution of LiHMDS (0.24 mL, 0.236 mmol) in THF (5 mL) -78 °C. After being stirred for 1 h at this temperature, [RuCl2(p-cymene)]2 (70 mg, 0.114 mmol) was added to the mixture. The mixture was allowed to warm and was stirred for 4 h. The solution was filtered through Celite and evaporated to dryness (70.4 mg). The 1H NMR spectrum showed a mixture, but the peaks due to 2c can be assigned as follows (CDCl3, 400 MHz): δ 1.04 (d, 3H, J 7.0, CHMeMe’), 1.13 (d, 3H, J 7.0, CHMeMe’), 1.77 (s, 3H, Me), 2.57 (sept, 1H, J 7.0, CHMeMe’), 3.08 (d, 1H, J 8.0, CH2), 3.72 (d, 1H, J 8.0, CH2), 4.97 (d, 1H, J 5.0, Cy), 5.02 (d, 1H, J 5.5, Cy), 5.25 (d, 1H, J 5.0, Cy), 5.31 (d, 1H, J 5.5, Cy), 7.35 (ddd, 1H, J 7.0, 5.5, 1.5, H5), 7.47 (d, 1H, J 7.0, H3), 7.74 (td, 1H, J 7.0, 1.0, H4), 8.91 (d, 1H, J 5.5, H6). Examination of the Coordination of Substituted Pyridines by 1H NMR Spectroscopy. A mixture of [MCl2Cp*]2 (M ) Ir, Rh) or [RuCl2(p-cymene)]2 (15 to 20 mg) and an equimolar amount of the appropriate ligand (2-acetylpyridine, 2-ethylpyridine, or 2-phenylpyridine) was dissolved in CD2Cl2 (or CDCl3). The 1H NMR spectra were recorded using a Bruker DRX (400 MHZ) at different temperatures. X-ray Crystal Structure Determinations. Details of the structure determinations of crystals of 1a,b, 2a,b, 4a,d, and 5 are given in Table 1; those for 4c are in the Supporting Information. Data were collected on a Bruker Apex 2000 CCD diffractometer using graphite-monochromated Mo KR radiation, λ ) 0.7107 Å. The data were corrected for Lorentz and polarization effects, and empirical absorption corrections were applied. The structures were solved by direct methods and with structure refinement on F2 employing SHELXTL version 6.10.25 Hydrogen atoms were included in calculated positions (CsH ) 0.93-1.00 Å, OsH ) 0.84 Å) riding on the bonded atom with isotropic displacement parameters set to 1.5Ueq (O) for hydroxyl H atoms, 1.5Ueq (C) for methyl hydrogen atoms, and 1.2Ueq (C) for all other H atoms. All non-hydrogen atoms were refined with anisotropic displacement parameters without positional restraints. In the cases of 4a and 5 disordered solvent molecules were removed by using the SQUEEZE option in Platon26 (solvent has been included in all formulas). Figures were drawn using the program ORTEP.27

Acknowledgment. We thank the Saudi Arabian government (O.A.-D.) for a studentship, EPSRC for funding (EP/ D055024/1), and Johnson Matthey for a loan of platinum metal salts. Supporting Information Available: Crystallographic data in CIF format for 1a,b, 2a,b, 4a,d, and 5. These materials are available free of charge via the Internet at http://pubs.acs.org. OM800909W (25) Bruker; Version 6.10 ed.; Bruker Inc.: Madison, WI, 1998-2000. (26) Spek, A. L. Acta Crystallogr., Sect. A 1990, A46, C-34. (27) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.