Expeditious Synthesis of [Au(NHC)(L)]+ (NHC = N ... - ACS Publications

Jul 28, 2010 - School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, United Kingdom. Organometallics , 2010, 29 (21), pp 5402–5408 ...
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Organometallics 2010, 29, 5402–5408 DOI: 10.1021/om100456b

Expeditious Synthesis of [Au(NHC)(L)]þ (NHC = N-Heterocyclic Carbene; L = Phosphine or NHC) Complexes† Sylvain Gaillard, Pierrick Nun, Alexandra M. Z. Slawin, and Steven P. Nolan* School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, United Kingdom Received May 11, 2010

The use of the versatile N-heterocyclic carbene (NHC) gold(I) hydroxide [Au(OH)(IPr)] (IPr = N,N0 -bis(2,6-diisopropylphenyl)imidazol-2-ylidene) as precursor permits the expedient synthesis of a series of cationic heteroleptic [Au(NHC)(NHC0 )]þ and [Au(NHC)(PR3)]þ complexes by protonolysis with the appropriate acid salts. Complete characterization by 1H and 13C NMR spectroscopy and by single-crystal X-ray diffraction was performed in order to discern electronic and structural differences between cationic heteroleptic [Au(NHC)(NHC0 )]þ and [Au(NHC)(PR3)]þ congeners.

Introduction A wide range of organometallic complexes is currently under evaluation for their anticancer properties.1 In this area, gold complexes are particularly attractive for their biological compatibility.2 The most frequently encountered ancillary ligands for these biologically active complexes are tertiary phosphines,3 N-heterocyclic carbenes (NHCs),4 or pyridine-based ligands.5 Recently, cationic bis-(NHC) gold(I) † Part of the Dietmar Seyferth Festschrift. Dedicated to Professor Dietmar Seyferth *To whom correspondence should be addressed. Fax: þ44 (0)1334 463763. Tel: þ44(0)1334 463808. E-mail: [email protected]. (1) (a) Hartinger, C. G.; Jakupec, M. A.; Zorbas-Seifried, S.; Groessi, M.; Egger, A.; Berger, W.; Zorbas, H.; Dyson, P. J.; Keppler, B. K. Chem. Biodiversity 2008, 5, 2140–2155. (b) Hannon, M. J. Pure Appl. Chem. 2007, 79, 2243–2261. (c) Abeysinghe, P. M.; Harding, M. M. Dalton Trans. 2007, 3474–3482. (d) Vessieres, A.; Top, S.; Beck, W.; Hillard, E.; Jaouen, G. Dalton Trans. 2006, 529–541. (e) Rademaker-Lakhai, J. M.; Van den Bongard, D; Pluim, D.; Beijnen, J. H.; Schellens, J. H. M. Clin. Cancer Res. 2004, 3717–3727. (2) (a) Milacic, V.; Dou, Q. P. Coord. Chem. Rev. 2009, 253, 1649– 1660. (b) Abdou, H. E.; Mohamed, A. A.; Fackler, J. P., Jr.; Burini, A.; Galassi, R.; L opez-de-Luzuriaga, J. M.; Olmos, M. E. Coord. Chem. Rev. 2009, 253, 1661–1669. (c) Ott, I. Coord. Chem. Rev. 2009, 253, 1670–1681. (3) For selected examples involving phosphine complexes, see: (a) Barnard, P. J.; Berners-Price, S. J. Coord. Chem. Rev. 2007, 251, 1889–1902. (b) Schuh, E.; Valiahdi, S. M.; Jakupec, M. A.; Keppler, B. K.; Chiba, P.; Mohr, F. Dalton Trans. 2009, 10841–10845. (c) Shoeib, T.; Atkinson, D. W.; Sharp, B. L. Inorg. Chim. Acta 2010, 363, 184–192. (4) For selected examples involving NHC complexes, see: (a) Ray, S.; Mohan, R.; Singh, J. K.; Samantaray, M. K.; Shaikh, M. M.; Panda, D.; Ghosh, P. J. Am. Chem. Soc. 2007, 129, 15042–15053. (b) Raubenheimer, H. G.; Cronje, S. Chem. Soc. Rev. 2008, 37, 1998–2011. (c) Hindi, K. M.; Panzer, M. J.; Cannon, C. L.; Youngs, W. J. Chem. Rev. 2009, 109, 3859– 3884. (d) Teyssot, M. L.; Jarousse, A. S.; Manin, M.; Chevry, A.; Roche, S.; Norre, F.; Beaudoin, C.; Morel, L.; Boyer, D.; Mahiou, R.; Gautier, A. Dalton Trans. 2009, 6894–6902. (5) For selected examples involving pyridine-based complexes, see: (a) Marcon, G.; Carotti, S.; Coronnello, M.; Messori, L.; Mini, E.; Orioli, P.; Mazzei, T.; Cinellu, M. A.; Minghetti, G. J. Med. Chem. 2002, 45, 1672–1677. (b) Messori, L.; Marcon, G.; Cinellu, M. A.; Coronnello, M.; Mini, E.; Gabbiani, C.; Orioli, P. Bioorg. Med. Chem. 2004, 12, 6039–6043. (c) Coronello, M.; Mini, E.; Caciagli, B.; Cinellu, M. A.; Bindoli, A.; Gabbiani, C.; Messori, L. J. Med. Chem. 2005, 48, 6761–6765. (d) Casini, A.; Diawara, M. C.; Scopelliti, R.; Zakeeruddin, S. M.; Gr€atzel, M.; Dyson, P. J. Dalton Trans. 2010, 39, 2239–2245.

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complexes were reported for their antimitochondrial activity.6 To the best of our knowledge, these cationic bis-(NHC) gold(I) complexes are homoleptic entities bearing the same NHC ligand, and only one example reported by Raubenheimer7 bears two different NHCs. This latter complex was obtained in low yields by repeated recrystallization from a symmetrical and unsymmetrical complex mixture. Homoleptic cationic bis-(NHC) gold(I) complexes are usually synthesized by transmetalation from the corresponding AgNHC complexes8 or by using two equivalents of the free NHC in a substitution reaction involving AuCl(DMS) (DMS = dimethylsulfide).9 In this manner, it appeared difficult to synthesize cationic heteroleptic bis-(NHC) gold(I) complexes of type [Au(NHC)(NHC0 )]þ. One very intriguing possibility arose during our synthetic exploration of the reaction chemistry involving [Au(OH)(IPr)] (1). As 1 exhibits a strongly basic character (pKa between 29 and 31), we have previously taken advantage of this alkaline character to react 1 with acidic protons.10 These C-H bond activation reactions are very straightforward as long as the reaction partner possesses a pKa in the proper range. In our continuing efforts aimed at developing simple and efficient syntheses of NHC gold complexes,11 we describe here an easy procedure leading to cationic heteroleptic bis-(NHC) gold(I)9c and (NHC)phosphane gold(I) complexes12 with various counterions (6) (a) Hickey, J. L.; Ruhayel, R. A.; Barnard, P. J.; Baker, M. V.; Berners-Price, S. J.; Filipovska, A. J. Am. Chem. Soc. 2008, 130, 12570– 12571. (b) Baker, M. V.; Barnard, P. J.; Berners-Price, S. J.; Brayshaw, S. K.; Hickey, B. W.; White, A. H. Dalton Trans. 2006, 3708–3715. (7) Raubenheimer, H. G.; Lindeque, L.; Cronje, S. J. Organomet. Chem. 1996, 511, 177–184. (8) (a) Wang, H. M. J.; Chen, C. Y. L.; Lin, I. J. B. Organometallics 1999, 18, 1216–1223. (b) Wang, H. M. J.; Vasam, C. S.; Tsai, T. Y. R.; Chen, S.-H.; Chang, A. H. H.; Lin, I. J. B. Organometallics 2005, 24, 486–493. (9) (a) Fr€ankel, R.; Kniczek, J.; Ponikwar, W.; N€ oth, H.; Polborn, K.; Fehlhammer, W. P. Inorg. Chim. Acta 2001, 312, 23–29. (b) Barnard, P. J.; Baker, M. V.; Berners-Price, S. J.; Skelton, B. W.; White, A. H. Dalton Trans. 2004, 1038–1047. (c) Baker, M. V.; Barnard, P. J.; Berners-Price, S. J.; Brayshaw, S. K.; Hickey, B. W.; White, A. H. Dalton Trans. 2006, 3708– 3715. (10) Gaillard, S.; Slawin, A. M. Z.; Nolan, S. P. Chem. Commun. 2010, 46, 2742–2744. r 2010 American Chemical Society

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Figure 1. NHC and tertiary phosphine ligands a-k and counterions a0 -c0 used in this study.

X- (X- = BF4- a0 , PF6- b0 , Cl- c0 ). Indeed, using the easily handled imidazolium or phosphonium salts, this silver-free synthetic route should be useful in preparing cationic heteroleptic gold(I) complexes for medicinal application. Moreover, the potential diversity of substituents afforded by the introduction of two different NHCs can assist in the finetuning of the lipophilicity (log P)9c,13 of these complexes, which appears to be an important parameter in the selectivity of these complexes toward cancer over normal cells.6a Synthesis and full characterization of complexes 3 and an analysis of the steric hindrance of different NHCs coordinated to the gold center (Figure 1), by calculating the buried volume (% VBur) value for these ligands in gold systems, are presented.

Results and Discussion Synthesis. As mentioned above, the basic nature of 1 suggested to us that acidic protons could be efficient partners in reactions leading to the replacement of the OH group and the activation of somewhat acidic C-H bonds.10 The pKa of imidazolium salts has been experimentally determined to be in the 23-25 pKa unit range.14 As the pKa of 1 is significantly higher, we reasoned that a deprotonation of imidazolium salt was possible and could lead in a straightforward manner to the formation of mixed NHC complexes. To test this hypothesis, 1 was reacted with 1 equiv of the imidazolium salt IPr 3 HBF4 (2ga0 ) in toluene at 70 °C during 48 h. This (11) (a) de Fremont, P.; Scott, N. M.; Stevens, E. D.; Nolan, S. P. Organometallics 2005, 24, 2411–2418. (b) de Fremont, P.; Stevens, E. D.; Fructos, M. R.; Daz-Requejo, M. M.; Perez, P. J.; Nolan, S. P. Chem. Commun. 2006, 2045–2047. (c) de Fremont, P.; Stevens, E. D.; Eelman, M. D.; Fogg, D. E.; Nolan, S. P. Organometallics 2006, 25, 5824–5828. (d) de Fremont, P.; Singh, R.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P. Organometallics 2007, 26, 1376–1385. (e) de Fremont, P.; Marion, N.; Nolan, S. P. J. Organomet. Chem. 2009, 694, 551–560. (f) Díez-Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612–3676. (g) Gaillard, S.; Slawin, A. M. Z.; Bonura, A. T.; Stevens, E. D.; Nolan, S. P. Organometallics 2010, 29, 394–402. (12) (a) B€ ohler, C.; Stein, D.; Donati, N.; Gr€ utzmacher, H. New J. Chem. 2002, 26, 1291–1295. (b) Baker, M. V.; Barnard, P. J.; Berners-Price, S. J.; Brayshaw, S. K.; Hickey, B. W.; Skelton, B. W.; White, A. H. J. Organomet. Chem. 2005, 690, 5625–5635. (c) P. Radloff, C.; Weigand, J. J.; Hahn, F. E. Dalton Trans. 2009, 9392–9394. (13) Trapp, S.; Horobin, R. W. Eur. Biophys. J. 2005, 34, 959–966. (14) (a) Bordwell, F. G. Acc. Chem. Res. 1988, 456–463. (b) Alder, R. W.; Allen, P. R.; Williams, S. J. J. Chem. Soc., Chem. Commun. 1995, 1267–1268. (c) Amyes, T. L.; Diver, S. T.; Richard, J. P.; Rivas, F. M.; Toth, K. J. Am. Chem. Soc. 2004, 126, 4366–4374.

Table 1. Synthesis of [Au(NHC)(NHC0 )][X] and [Au(NHC)(PR3)][X] 3 Complexesa

entry

salts L 3 HX 2

complex 3 T (°C) t (h) conv (%) yield (%)

BMIM 3 HBF4, 2aa 3aa0 25 14 100 93 3ab0 25 14 100 95 BMIM 3 HPF6, 2ab0 0 0 3ac 25 14 100 94 BMIM 3 HCl, 2ac 3ba0 25 24 100 91 ICy 3 HBF4, 2ba0 3ca0 70 48 77 0 IAd 3 HBF4, 2ca0 3da0 80 24 100 95 ItBu 3 HBF4, 2da0 3ea0 70 48 100 97 IMes 3 HBF4, 2ea0 3fa0 70 48 81 59 SIMes 3 HBF4, 2fa0 3ga0 70 48 100 95 IPr 3 HBF4, 2ga0 3ha0 80 24 50 0 SIPr 3 HBF4, 2ha0 3ia0 25 14 100 89 P(tBu)3 3 HBF4, 2ia0 0 0 3ja 25 14 100 90 P(nBu)3 3 HBF4, 2ja 3ka0 25 14 100 91 P(Ph)3 3 HBF4, 2ka0 a Reaction conditions: Complex 1 (0.166 mmol) and imidazolium or phosphonium salts 2 (0.166 mmol) were reacted in toluene (1.7 mL) under conditions reported. 1 2 3 4 5 6 7 8 9 10 11 12 13

0

reaction, with reaction times being unoptimized at this stage, led to the isolation of [Au(IPr)2][BF4] (3ga0 ) in a 95% isolated yield (eq 1).

To expand on this initial discovery, further reactivity of 1 was tested with various NHC salts bearing the BF4- anion, a0 . To explore whether this approach was general, other counterions, such as PF6- (b0 ) and Cl- (c0 ) were also examined. The aromatic nature of the substituents on the NHCnitrogen atoms was then put into question, and further reactivity tests involving 1 and nonaromatic-containing NHCs as well as phosphonium salts were also performed. For each complex 3, temperature and reaction time were optimized in toluene.15 Results of these optimization reactions leading to 3 are summarized in Table 1. (15) THF can also be used, but this reaction yielded pinkish instead of white powders in toluene. We suspect the color develops from the generation of gold nanoparticles under these experimental conditions.

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Table 2. 13C Chemical Shift of Carbenic Carbon for NHC in Complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 a entry

complex

δC1b (ppm)

δC2c (ppm)

1 2 3 4 5 6 7 8 9 10 11

[Au(IPr)(BMIM)][BF4], 3aa0 [Au(IPr)(BMIM)][PF6], 3ab0 [Au(IPr)(BMIM)][Cl], 3ac0 [Au(IPr)(ICy)][BF4], 3ba0 [Au(IPr)(ItBu)][BF4], 3da0 [Au(IPr)(IMes)][BF4], 3ea0 [Au(IPr)(SIMes)][BF4] 3fa0 [Au(IPr)(IPr)][BF4], 3ga0 [Au(IPr)(P(tBu)3)][BF4], 3ia0 [Au(IPr)(P(nBu)3)][BF4], 3ja0 [Au(IPr)(P(Ph)3)][BF4], 3ka0

188.0 188.0 188.0 187.0 185.5 186.1 186.7d 184.2 191.9 (111.9 Hz)e 191.6 (122.0 Hz)e 188.2 (126.4 Hz)e

181.1 181.3 180.6 178.5 179.6 183.1 205.2d 184.2

a 13 C NMR recorded in CDCl3. b δC1 is the signal attributed to IPr, g. δC2 is the signal attributed to other NHCs a-g. d 13C NMR recorded in CD2Cl2. e Coupling constant between the carbenic carbon atom of IPr (g) and the phosphorus atom of phosphanes i-k are in parentheses. c

Under these reaction conditions, all imidazolium and phosphonium salts 2 reacted with 1. However, imidazolium salts 2ca0 , 2fa0 , and 2ha0 did not proceed to complete product conversion (entries 5, 8, and 10, Table 1). In spite of this, complex 3fa0 was successfully isolated by crystallization from a mixture of the imidazolium salt 2fa0 and the product 3fa0 with a 59% yield (Table 1, entry 8), whereas such attempts failed with complexes 3ca0 and 3ha0 (Table 1, entries 5 and 10). These two latter examples were simply observed in the 1 H NMR spectrum of the reaction crude. Even when harsher reaction conditions were employed, the conversion for these complexes was never increased, presumably due to limitations associated with the important hindrance between the IAd (c) and SIPr (h) with the IPr (g) ligand. Moreover, all imidazolium salts providing hindered NHCs such as c-h needed heating (70 or 80 °C) to facilitate the reaction and generation of the desired product (entries 5-9, Table 1). For the smaller NHCs such as a and b and more surprisingly phosphines i-k (even if a tertiary phosphine such as i is viewed as very sterically encumbering) reactions can be carried out at room temperature to give the corresponding 3 in high isolated yields (89% to 94%) (Table 1, entries 1-4 and 11-13). Noteworthy, to our knowledge, complexes 3ia0 and 3ja0 are the first examples of cationic trialkylphosphineNHC gold(I) complexes. Indeed, only three examples of mixed tertiary phosphine-NHC gold(I) have been reported (tertiary phosphine = PPh3 or diphenylphosphinoethane, dppe).12 NMR Spectroscopy. The 1H NMR spectra of complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 , recorded in CDCl3, displayed a singlet between 7.11 and 7.64 ppm assigned to the two protons of the backbone of IPr (g). This wide range of values can be divided into three categories that depend on the associated co-ancillary ligand. Indeed, with the N-alkyl-substituted NHC, i.e., BMIM (a), ICy (b), and ItBu (d), values are between 7.38 and 7.44 ppm. For N-arylsubstituted NHC, i.e., IMes (e), SIMes (f), and IPr (g), signals are observed between 7.11 and 7.24 ppm. Finally, phosphine ligands i-k lead to chemical shifts of these protons in a very low field compared to NHC, with values ranging between 7.50 and 7.64 ppm. The 31P NMR spectra of coordinated phosphine ligands i-k displayed a sharp singlet with a chemical shift (δP) of 90.7, 29.7, and 40.0 ppm for PtBu3 (i), PnBu3 (j), and PPh3 (k), respectively. For the δP of the triphenylphosphine, the value is in good agreement with data found in the literature, with δP reported at 39.67 and

42.2 ppm for [Au(ItBu)(PPh3)][PF6]12b and a bistropNHC gold complex (bistropNHC = 1,3-bis(5H-dibenzo[a,d]cycloheptene-5-yl)imidazol-2-ylidene),12a respectively. For the 13C NMR, resonances of the carbenic carbon atoms of NHC ligands in complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 3ka0 are summarized in Table 2. The chemical shifts of carbenic carbons of the common IPr (g) (δC1) in cationic bis-(NHC) gold(I) complexes 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 displayed a singlet between 184.2 and 188.0 ppm (Table 2, entries 1-8). The chemical shifts of the carbenic carbons of the other NHCs (δC2) in cationic bis(NHC) gold(I) complexes 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 exhibit a signal between 180.6 and 205.2 ppm (Table 2, entries 1-8). The comparison of δC1 in 3aa0 , 3ab0 , and 3ac0 appears to confirm that the counterion has little effect on this spectroscopic feature (Table 2, entries 1-3). Indeed the δC1 values of IPr (g) in complexes 3aa0 -3ac0 were exactly the same (188.0 ppm), and only a very small variation in the δC2 of the BMIM (a) was observed, with values between 180.6 and 181.3 ppm. Due to the strong σ donation of the NHC ligand,16 the presence of two NHCs on the gold(I) center resulted in a δC1 at very low field for cationic bis-(NHC) gold(I) complexes 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 compared to the acetonitrile-containing cationic (NHC) gold(I) relatives previously reported (δC = 165.9 ppm for [Au(IPr)(CH3CN)][BF4]).11e Interestingly, if the same comparison can be made with neutral gold(I) halide (δC = 175.5 for [AuCl(IPr)]17 and 179.0 ppm for [AuBr(IPr)]11d), the δC1 values of IPr (g) in 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 are also at lower field, meaning that even if the gold center is cationic, these complexes appear to be less Lewis acidic than the neutral gold(I) halide and acetonitrile-containing cationic NHC gold(I) complexes.18 For cationic phosphine-(NHC) gold(I) complexes 3ia0 -3ka0 , δC1 of IPr (g) was found in the 188.2 to 191.9 ppm range (Table 2, entries 9-11), which is found at slightly lower field than the cationic bis-(NHC) gold(I) complexes 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 . Coupling constants between carbenic carbon atom and phosphorus atom of complexes 3ia0 -3ka0 were measured between 111.9 and 126.4 Hz (Table 2, entries 9-11). Crystallographic Data. To unequivocally determine the structure and permit the examination of metrical variations associated with the nature of the ligands a, b, d-g, and i-k, single crystals of compounds were prepared by slow diffusion of Et2O in a saturated solution of complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 in CH2Cl2 or CHCl3 and subjected to X-ray diffraction (XRD).19 Ball-and-stick representations of 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 are presented in Figure 2. All cationic bis-(NHC) gold(I) complexes 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 are linear, as expected for cationic gold(I) (16) (a) Huang, J.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 2674–2678. (b) Kelly, R. A., III; Clavier, H.; Guidice, S.; Scott, N. M.; Stevens, D.; Bordner, J.; Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P. Organometallics 2008, 27, 2002–2010. (17) Fructos, M. R.; Belderrain, T. R.; de Fremont, P.; Scott, N. M.; Nolan, S. P.; Daz-Requejo, M. M.; Perez, P. J. Angew. Chem., Int. Ed. 2005, 44, 5284–5288. (18) (a) Herrmann, W. A.; Runte, O.; Artus, G. J. Organomet. Chem. 1995, 501, C1–C4. (b) Tapu, D.; Dixon, D. A.; Roe, C. Chem. Rev. 2009, 109, 3385–3407. (19) CCDC 773700 for complex 3ga and CCDC 776375-776384 for complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

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Figure 2. Ball-and-stick representations of [Au(IPr)(BMIM)][BF4], 3aa0 , [Au(IPr)(BMIM)][PF6], 3ab0 , [Au(IPr)(BMIM)][Cl], 3ac0 , [Au(IPr)(ICy)][BF4], 3ba0 , [Au(IPr)(ItBu)][BF4], 3da0 , [Au(IPr)(IMes)][BF4], 3ea0 , [Au(IPr)(SIMes)][BF4], 3fa0 , [Au(IPr)(IPr)][BF4], 3ga0 , [Au(IPr)(tBu3P)][BF4], 3ia0 , [Au(IPr)(nBu3P)][BF4], 3ja0 , and [Au(IPr)(Ph3P)][BF4], 3ka0 . Some H atoms are omitted for clarity. Selected bond distances (A˚) and angles (deg) are summarized in Table 3.

complexes bearing two ancillary ligands. This is confirmed by the C1-Au-C31 with values measured between 176.7(2)° and 179.6(7)° (Table 3, entries 1-8). For cationic (NHC)tertiary phosphine gold(I) complexes 3ia0 -3ka0 , these angles were slightly distorted with angles between 174.6° and 177.2° (Table 3, entries 9-11). The C1-Au bond distances of IPr (g) in 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 have a wide range and fall between 2.003(7) and 2.079(14) A˚ depending on the steric hindrance and the electronic effect of the coligands (NHC or tertiary phosphine). The principal difference characterizing these structures deals with the N5C1-C31-N32 interplanar dihedral angle between the two imidazole rings in 3aa0 -3ac0 , 3ba0 , and 3da0 -3ga0 . With the smallest ligands, i.e., ICy (b) or ItBu (d), this angle is less than

10°, showing almost a coplanarity of the two imidazole rings (Table 3, entries 4 and 5). With IMes (e), SIMes (f) or IPr (g), which are among the bulkiest ligands, this angle is more than 40° and reaches 55.7° for SIMes (f) (Table 2, entries 6-8), reflecting a significant torsion between the two imidazole rings of the NHC ligands. Surprisingly, the most important torsion angle (86.9(1)°) reported was for the complex [Au(ItBu)][Cl].9c However, this angle is completely different when the cationic gold(I) center bears IPr (g) and ItBu (d) such as in complex 3da0 , which revealed an angle between 1.6° and 8.2° (Table 3, entry 5). The Au-P bond distances measured in 3ia0 -3ka0 were found in the 2.285(4) to 2.3145(18) A˚ range. These values are in good agreement with those found in 3ja0 and 3ka0 and compare well with Au-P

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Table 3. Au-C1, Au-C31, and Au-P Bond Distances, C1-Au-C31 and C1-Au-P Angles, and N1-C1-C31-N35 and N2-C1-C31-N32 Torsion Angles for Crystallized Complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0

entry

complex 3

1 2 3 4 5

[Au(IPr)(BMIM)][BF4], 3aa0 [Au(IPr)(BMIM)][PF6], 3ab0 [Au(IPr)(BMIM)][Cl], 3ac0 [Au(IPr)(ICy)][BF4], 3ba0 [Au(IPr)(ItBu)][BF4], 3da0

6 7 8 9

[Au(IPr)(IMes)][BF4], 3ea0 [Au(IPr)(SIMes)][BF4], 3fa0 [Au(IPr)(IPr)][BF4], 3ga0 [Au(IPr)(tBu3P][BF4], 3ia0

10

[Au(IPr)(nBu3P)][BF4], 3ja0

11

[Au(IPr)(Ph3P)][BF4], 3ka0

distance Au-CI (A˚)

distance Au-C31 or Au-P (A˚)

angle C1-Au-C31 or C1-Au-P (deg)

2.019(6) 2.025(6) 2.022(6) 2.003(7) 2.038(17) 2.006(18) 2.028(5) 2.010(10) 2.027(8) 2.044(7) 2.033(7) 2.070(14) 2.079(14) 2.039(5)

2.018(6) 2.018(6) 2.026(6) 2.017(7) 2.10(2) 2.05(2) 2.034(6) 2.032(10) 2.024(7) 2.3145(18) 2.3061(16) 2.285(4) 2.295(4) 2.2939(15)

177.9(3) 178.8(3) 176.7(2) 178.1(3) 179.6(7) 177.2(7) 179.38(19) 177.3(3) 178.3(3) 176.23(19) 176.25(18) 177.2(4) 176.6(5) 174.62(12)

bond distances previously observed in phosphine-(NHC) complexes (2.274(1) to 2.299(2) A˚).12 For complex 3ia0 , this bond is slightly longer certainly because of the hindrance generated by the tBu substituents on the phosphorus atom. Percent Buried Volume (%VBur). To gain a more quantitative understanding of the steric effects present in the reported complexes, the steric hindrance and pressure brought about by the NHC ligands a, b, and d-g and phosphine ligands i-k around the gold center were examined using the recently disclosed %Vbur model.20 Indeed, such data could be of interest and help explain the availability of coordination space about the metal center in an eventual thiol or selenol binding event. Such processes are apparently involved in the inhibition displayed by gold complexes to thioredoxin and the enzyme glutathione reductase.6a,21 To quantify this steric influence, the percent buried volume of each of these ligands was calculated using the SambVca method developed by Cavallo and co-workers.22 In this model, the %VBur value represents the portion of a sphere, centered on the metal atom, occupied by the ligand (Figure 3). The %VBur values of IPr (g) in complexes 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 are in a range between 38.4 and 45.5 (Table 4). For ligands a, b, d-g, and i-k, these calculated values were found between 27.2 and 37.8 for ICy (b) (20) Poater, A.; Cosenza, B.; Correa, A.; Giudice, S.; Ragone, F.; Scarano, V.; Cavallo, L. Eur. J. Inorg. Chem. 2009, 1759–1766. (21) Urig, S.; Fritz-Wolf, K.; Reau, R.; Herold-Mende, C.; T oth, K.; Davioud-Charvet, E.; Becker, K. Angew. Chem., Int. Ed. 2006, 45, 1881– 1886. (22) The Web-based free-access SambVca software is available online at http://www.molnac.unisa.it/OMtools/sambvca.php. (23) For the values obtained using the XRD-determined bond length for Au-C of each complex see the Supporting Information.

angle N1-C1-C31-N35 (deg)

angle N2-C1-C31-N32 (deg)

12.6 20.8 18.9 0.8 1.6 1.8 38.7 55.5 47.0

16.2 22.7 19.4 1.8 8.2 5.9 43.4 51.8 38.5

Figure 3. Graphical representation of the sphere used for the % VBur calculations. Table 4. Steric Parameter (%VBur) Calculated for NHCs a, b, and d-g and Phosphane i-k in [Au(IPr)(L)][X] 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 entry complex ligand %VBur of ga 1 2 3 4 5

3aa0 3ab0 3ac0 3ba0 3da0

IPr, g IPr, g IPr, g IPr, g IPr, g

6 7 8 9

3ea0 3fa0 3ga0 3ia0

IPr, g IPr, g IPr, g IPr, g

10

3ja0

IPr, g

11

3ka0

IPr, g

a

42.3 41.6 41.7 43.9 38.4 39.7 45.4 45.5 40.4 42.7 43.0 45.0 44.6 44.7

ligand BMIM, a BMIM, a BMIM, a ICy, b ItBu, d IMes, e SIMes, f IPr, g PtBu3, i PnBu3, j PPh3, k

%VBur of La %VBur tot 27.6 28.1 29.1 27.2 37.8 37.7 35.1 35.9 37.7 37.0 37.8 30.6 31.5 31.1

70.0 69.6 70.5 71.1 75.8 77.0 80.5 81.3 77.6 79.6 80.4 75.2 75.7 75.8

Calculation were achieved using the crystallographically determined bond length for Au-Ccarbene, and the radius of the sphere was fixed at R = 3.5 A˚.23

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Organometallics, Vol. 29, No. 21, 2010

and ItBu (d) or PtBu3 (i), respectively (Table 4, entries 1, 5, and 9). If now both ligands are considered in 3aa0 -3ac0 , 3ba0 , 3da0 -3ga0 , and 3ia0 -3ka0 and the %VBur of the two ligands are added to estimate the total buried volume of ligands (%VBur tot) around the gold center, values were found ranging from 69.6 to 81.3 (Table 2) for BMIM (a) and SIMes (f), respectively. The highest %VBur tot value was found for 3fa0 and can somewhat explain why its synthesis proved problematic. (Table 1, entry 8). A similar explanation can rationalize the experimental failures observed for complexes 3ca0 and 3ha0 , where ligand c and h are well known to be among the bulkiest NHCs (Table 1, entries 5, 8, and 10).11f Noteworthy, all cationic bis-(NHC) gold(I) with %VBur tot lower than 71.1 such as complexes 3aa0 -3ba0 are synthesized at room temperature, whereas the ones with %VBur tot higher than 75.8 required heating. This experimental requirement is logical on the basis of the steric analysis provided above. In the case of cationic (NHC)-phosphine ligands 3ia0 -3ka0 , the %VBur tot can be higher than in the case of cationic bis-(NHC) ligands without affecting the reaction conditions, presumably because of the very different ligand geometry. In conclusion, we have developed a silver-free synthesis to cationic bis-(NHC) gold(I) complexes bearing two different NHCs. These reactions are usually charged and conducted in air! This synthetic route involves a C-H activation of an easily handled imidazolium salt reacting with an air- and moisture-stable gold(I) hydroxide complex (1) with formation of water as byproduct. This efficient synthesis of cationic heteroleptic gold(I) complexes could help generate a large library of gold complexes possessing a wide range of lipophilic properties. This method can also be extended to cationic (NHC)-tertiary phosphine gold(I) complexes using phosphonium salt instead of the NHC salt. Phosphonium salts as reactants constitute an interesting development due to their ease of handling when compared to their corresponding tertiary phosphine relatives, some of which are prone to facile air-oxidation. For all complexes described, biological testing for anticancer activity is ongoing.

Experimental Section General Considerations. All reactions were carried out in air unless otherwise stated. Technical solvents were used and purchased from Aldrich. NMR spectra were recorded on a 400 MHz Bruker spectrometer. Elemental analyses were performed by the analytical services at the University of St Andrews. Synthesis of [Au(IPr)(L)][X] (3). [Au(OH)(IPr)] (1) (100 mg, 0.166 mmol) and L 3 HX 2 (0.166 mmol) were introduced into a vial containing toluene (1.7 mL) and a stir bar. The reaction was stirred at the temperature and time as indicated in Table 1. Pentane (2 mL) was added, and the resulting precipitate was collected on a frit. The solid was washed with pentane (3  3 mL) and dried under vacuum to afford 3 as a white microcrystalline solid. Synthesis of [Au(IPr)(BMIM)][BF4] (3aa0 ). The general procedure afforded 3aa0 as a white microcrystalline solid (125.1 mg, 93%). 1H NMR (300 MHz, CDCl3): δ 7.53 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.42 (s, 2H, CH imidazole IPr), 7.33 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 7.07 (d, J = 1.7 Hz, 1H, CH imidazole BMIM), 6.90 (d, J = 1.7 Hz, 1H, CH imidazole BMIM), 3.49 (t, J = 7.1 Hz, 2H, N-CH2 butyl BIMIM), 3.12 (s, 3H, N-CH3 BMIM), 2.54 (sept, J = 6.7 Hz, 4H, CH(CH3)2), 1.35-1.20 (m, 2H, overlapping CH2 butyl BMIM), 1.27 (d, J = 6.7 Hz, 12H, CH(CH3)2), 1.26 (d, J = 6.9 Hz, 12H, CH(CH3)2), 0.96-0.81 (m, 2H, CH2 butyl BMIM), 0.73 (t, J = 7.1 Hz, 3H, butyl BMIM) ppm. 19F NMR (282 Hz, CDCl3): -154.2 (s, BF4)

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-152.3 (s, BF4) ppm. 13C NMR (100 MHz, CDCl3): δ 188.0 (s, C carbene), 181.3 (s, C carbene), 145.8 (s, C aromatic IPr), 133.6 (s, C aromatic IPr), 130.9 (s, CH imidazole IPr), 124.3 (CH aromatic IPr), 124.2 (s, CH aromatic IPr), 124.3 (s, CH imidazole BMIM), 121.5 (s, CH imidazole BMIM), 50.6 (s, N-CH2 BMIM), 36.9 (s, N-CH3 BMIM), 33.1 (s, CH2 BMIM), 28.8 (s, CH(CH3)2), 24.6 (s, CH(CH3)2), 24.0 (s, CH(CH3)2), 19.4 (s, CH2 BMIM), 13.5 (s, CH3 butyl BMIM) ppm. Anal. Calcd for C35H50AuBF4N4: C, 51.86; H, 6.22; N, 6.91. Found: C, 51.76; H, 6.14; N, 6.81. Synthesis of [Au(IPr)(BMIM)][PF6] (3ab0 ). The general procedure afforded 3ab0 as a white microcrystalline solid (137.4 mg, 95%). 1H NMR (400 MHz, CDCl3): δ 7.56 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.38 (s, 2H, CH imidazole IPr), 7.35 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 6.98 (d, J = 1.8 Hz, 1H, CH imidazole BMIM), 6.87 (d, J = 1.8 Hz, 1H, CH imidazole BMIM), 3.50 (t, J = 7.2 Hz, 2H, N-CH2 butyl BIMIM), 3.12 (s, 3H, N-CH3 BMIM), 2.55 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.31-1.25 (m, 26H, 2H of CH2 butyl BMIM and 24H of CH(CH3)2), 0.95-0.84 (m, 2H, CH2 butyl BMIM), 0.74 (t, J = 7.2 Hz, 3H, butyl BMIM) ppm. 19F NMR (282 Hz, CDCl3): -74.0 (dd, J = 712.1, 2.9 Hz, 6F, PF6) ppm. 13C NMR (75 MHz, CDCl3): δ 188.0 (s, C carbene), 180.6 (s, C carbene), 145.9 (s, C aromatic IPr), 133.7 (s, C aromatic IPr), 131.0 (s, CH imidazole IPr), 124.3 (CH aromatic IPr), 123.2 (s, CH imidazole BMIM), 121.5 (s, CH imidazole BMIM), 50.7 (s, N-CH2 BMIM), 36.9 (s, N-CH3 BMIM), 33.1 (s, CH2 BMIM), 28.9 (s, CH(CH3)2), 24.7 (s, CH(CH3)2), 24.1 (s, CH(CH3)2), 19.5 (s, CH2 BMIM), 13.6 (s, CH3 butyl BMIM) ppm. Anal. Calcd for C35H50AuClN4: C, 48.39; H, 5.80; N, 6.45. Found: C, 48.32; H, 5.91; N, 6.23. Synthesis of [Au(IPr)(BMIM)][Cl] (3ac0 ). The general procedure afforded 3ac0 as a white microcrystalline solid (118.4 mg, 94%). 1H NMR (400 MHz, CDCl3): δ 7.54 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.52(d, J = 2.0 Hz, 1H, CH imidazole BMIM), 7.41 (s, 2H, CH imidazole IPr), 7.33 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 7.02 (d, J = 1.7 Hz, 1H, CH imidazole BMIM), 3.53 (t, J = 7.1 Hz, 2H, N-CH2 butyl BMIM), 3.22 (s, 3H, N-CH3 BMIM), 2.54 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.34-1.22 (m, 26H, 2H of CH2 butyl BMIM and 24H of CH(CH3)2), 0.94-0.84 (m, 2H, CH2 butyl BMIM), 0.73 (t, J = 7.2 Hz, 3H, butyl BMIM) ppm. 13C NMR (75.5 MHz, CDCl3): δ 188.0 (s, C carbene), 181.1 (s, C carbene), 145.7 (s, C aromatic IPr), 133.5 (s, C aromatic IPr), 130.9 (s, CH imidazole IPr), 124.2 (CH aromatic IPr), 124.1 (s, CH aromatic IPr), 123.8 (s, CH imidazole BMIM), 121.4 (s, CH imidazole BMIM), 50.5 (s, N-CH2 BMIM), 37.0 (s, N-CH3 BMIM), 33.1 (s, CH2 BMIM), 28.7 (s, CH(CH3)2), 24.6 (s, CH(CH3)2), 24.0 (s, CH(CH3)2), 19.4 (s, CH2 BMIM), 13.5 (s, CH3 butyl BMIM) ppm. Anal. Calcd for C35H50AuClN4: C, 55.37; H, 6.64; N, 7.38. Found: C, 55.25; H, 6.49; N, 7.23. Synthesis [Au(IPr)(ICy)][BF4] (3ba0 ). The general procedure afforded 3ba0 as a white microcrystalline solid (136.7 mg, 91%). 1 H NMR (400 MHz, CDCl3): δ 7.60 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.41-7.36 (m, 6H, 2H of CH imidazole IPr and 4H of CH aromatic IPr), 7.03 (s, 2H, CH imidazole ICy), 3.54-3.43 (m, 2H, N-CH ICy), 2.58 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.75-1.66 (m, 4H, CH2 ICy), 1.75-1.66 (m, 6H, CH2 ICy), 1.46-1.35 (m, 4H, CH2 ICy), 1.29 (d, J = 6.8 Hz, 24H CH(CH3)2 IPr), 1.16-1.04 (m, 2H, CH2 ICy), 1.00-0.88 (m, 4H, CH2 ICy) ppm. 19F NMR (376 Hz, CDCl3): -154.2 (s, BF4), -154.3 (s, BF4) ppm. 13C NMR (100 MHz, CDCl3): δ 187.0 (s, C carbene), 178.5 (s, C carbene), 145.9 (s, C aromatic IPr), 133.6 (s, C aromatic IPr), 130.9 (s, CH aromatic IPr), 124.6 (s, CH imidazole IPr), 124.3 (CH aromatic IPr), 118.6 (s, CH imidazole ICy), 60.6 (s, N-CH2 ICy), 36.6 (s, CH2 ICy), 28.7 (s, CH(CH3)2), 24.8 (s, CH(CH3)2), 24.8 (s, CH2 ICy), 24.4 (s, CH2 ICy), 23.6 (s, CH(CH3)2) ppm. Anal. Calcd for C42H60AuBF4N4: C, 55.76; H, 6.68; N, 6.19. Found: C, 55.62; H, 6.52; N, 6.31.

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Synthesis of [Au(IPr)(ItBu)][BF4] (3da0 ). The general procedure afforded 3da0 as a white microcrystalline solid (107.4 mg, 95%). 1H NMR (400 MHz, CDCl3): δ 7.55 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.44 (s, 2H, CH imidazole IPr), 7.34 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 7.12 (s, 2H, CH imidazole ItBu), 2.65 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.28 (s, 18H, C(CH3)3 ItBu), 1.26 (d, J = 6.9 Hz, 12H, CH(CH3)2), 1.24 (d, J = 6.9 Hz, 12H, CH(CH3)2) ppm. 19F NMR (282 Hz, CDCl3): -154.4 (s, BF4), -154.5 (s, BF4) ppm. 13C NMR (75 MHz, CDCl3): δ 185.5 (s, C carbene), 179.6 (s, C carbene), 145.4 (s, C aromatic IPr), 134.4 (s, C aromatic IPr), 130.8 (s, CH imidazole IPr), 124.6 (CH imidazole IPr), 124.6 (s, CH aromatic IPr), 117.7 (s, CH imidazole ItBu), 58.0 (s, N-C ItBu), 31.6 (s, CH3 ItBu), 28.8 (s, CH(CH3)2), 24.6 (s, CH(CH3)2), 23.6 (s, CH(CH3)2) ppm. Anal. Calcd for C38H56AuBF4N4: C, 53.53; H, 6.62; N, 6.57. Found: C, 53.32; H, 6.34; N, 6.89. Synthesis of [Au(IPr)(IMes)][BF4] (3ea0 ). The general procedure afforded 3ea0 as a white microcrystalline solid (158.4 mg, 97%). 1H NMR (400 MHz, CDCl3): δ 7.54 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.24 (s, 2H, CH imidazole IPr), 7.16 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 7.02 (s, 2H, imidazole IMes), 6.77 (s, 4H, CH aromatic IMes), 2.39 (s, 6H, CH3 IMes), 2.28 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.68 (s, 12H, CH3 IMes), 1.12 (d, J = 6.9 Hz, 12H, CH(CH3)2), 0.86 (d, J = 6.9 Hz, 12H, CH(CH3)2) ppm. 19F NMR (376 Hz, CDCl3): -154.9 (s, BF4), -155.0 (s, BF4) ppm. 13C NMR (75 MHz, CDCl3): δ 186.1 (s, C carbene), 183.1 (s, C carbene), 145.1 (s, C aromatic IPr), 139.1 (s, C aromatic IMes), 134.1 (s, C aromatic IPr), 133.9 (s, C aromatic IMes), 133.4 (s, C aromatic IMes), 130.5 (s, CH aromatic IPr), 129.5 (s, CH aromatic IMes), 124.2 (CH imidazole IPr), 123.8 (s, CH aromatic IPr), 123.6 (s, CH imidazole IMes), 28.4 (s, CH(CH3)2), 23.9 (s, CH(CH3)2), 23.7 (s, CH(CH3)2) 21.1 (s, CH3 IMes), 17.0 (s, CH3 IMes) ppm. Anal. Calcd for C48H60AuBF4N4: C, 59.02; H, 6.19; N, 5.74. Found: C, 59.35; H, 5.84; N, 5.41. Synthesis of [Au(IPr)(SIMes)][BF4] (3fa0 ). The general procedure with complex 1 (30 mg, 0.0050 mmol) and SIMes 3 HBF4 (2fa0 ) (39.3 mg, 0.10 mmol) afforded crude 3fa0 , which passed in solution in dichloromethane through a pad of silica and crystallized by slow gas diffusion of Et2O into a solution of crude 3fa0 in dichloromethane to afford colorless crystals (28.9 mg, 59%). 1H NMR (400 MHz, CD2Cl2): δ 7.56 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.18 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 7.15 (s, 2H, CH imidazole IPr), 6.74 (s, 4H, CH aromatic SIMes), 3.76 (s, 4H, CH2 imidazole SIMes), 2.34 (s, 6H, CH3 SIMes), 2.24 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.90 (s, 12H, CH3 SIMes), 1.09 (d, J = 6.9 Hz, 12H, CH(CH3)2), 0.87 (d, J = 6.9 Hz, 12H, CH(CH3)2) ppm. 19F NMR (376 Hz, CD2Cl2): -154.0 (s, BF4), -154.0 (s, BF4) ppm. 13C NMR (100 MHz, CD2Cl2): δ 205.2 (s, C carbene SIMes), 186.7 (s, C carbene IPr), 145.5 (s, C aromatic IPr), 138.7 (s, C aromatic SIMes), 135.4 (s, C aromatic IPr), 134.2 (s, C aromatic SIMes), 133.8 (s, C aromatic SIMes), 131.0 (s, CH aromatic IPr), 130.3 (s, CH aromatic SIMes), 124.4 (s, CH aromatic IPr), 124.4 (CH imidazole IPr), 51.7 (s, CH2 imidazole SIMes), 28.9 (s, CH(CH3)2), 24.1 (s, CH(CH3)2), 23.9 (s, CH(CH3)2) 21.3 (s, CH3 SIMes), 17.6 (s, CH3 SIMes) ppm. Anal. Calcd for C48H62AuBF4N4: C, 58.90; H, 6.38; N, 5.72. Found: C, 58.74; H, 6.02; N, 5.66. Synthesis of [Au(IPr)2][BF4] (3ga0 ). The general procedure afforded 3ga0 as a white microcrystalline solid (168.0 mg, 95%). 1H NMR (400 MHz, CDCl3): δ 7.45 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.11 (s, 2H, CH imidazole IPr), 7.09 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 2.27 (sept, J = 6.9 Hz, 4H, CH(CH3)2), 1.04 (d, J = 6.9 Hz, 12H, CH(CH3)2), 0.83 (d, J = 6.9 Hz, 12H, CH(CH3)2) ppm. 19F NMR (282 Hz, CDCl3): -151.0 (s, BF4), -151.1 (s, BF4) ppm. 13C NMR (100 MHz, CDCl3): δ 184.2 (s, C carbene), 145.0 (s, C aromatic IPr), 133.9 (s, C aromatic IPr), 130.7 (s, CH aromatic IPr), 125.2 (CH imidazole IPr), 124.3 (s, CH aromatic IPr), 28.5 (s, CH(CH3)2),

Gaillard et al. 24.2 (s, CH(CH3)2), 24.0 (s, CH(CH3)2) ppm. Anal. Calcd for C54H72AuBF4N4: C, 61.13; H, 6.84; N, 5.28. Found: C, 60.95; H, 6.80; N, 5.31. Synthesis of [Au(IPr)(PtBu3)][BF4] (3ia0 ). The general procedure afforded 3ia0 as a white microcrystalline solid (129.2 mg, 89%). 1H NMR (300 MHz, CDCl3): δ 7.57 (d, J = 0.6 Hz, 2H, CH imidazole IPr), 7.51 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.30 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 2.58 (sept, J = 6.7 Hz, 4H, CH(CH3)2), 1.26 (app t, J = 7.3 Hz, 24H, CH(CH3)2), 1.13 (d, J = 13.7 Hz, 27H, C(CH3)3 PtBu3) ppm. 31P NMR (121 Hz, CDCl3): δ 90.7 (s, tBu3P) ppm. 19F NMR (282 Hz, CDCl3): δ -154.8 (m, BF4) ppm. 13C NMR (100 MHz, CDCl3): δ 191.9 (d, J = 111.9 Hz, C carbene), 145.6 (s, C aromatic IPr), 133.8 (s, C aromatic IPr), 131.0 (s, CH aromatic IPr), 125.0 (d, J = 2.6 Hz, CH imidazole IPr), 124.2 (s, CH aromatic IPr), 39.2 (d, J = 18.3 Hz, C P(tBu)3), 31.7 (d, J = 3.7 Hz, CH3 P(tBu)3), 28.9 (s, CH(CH3)2), 24.5 (s, CH(CH3)2), 24.2 (s, CH(CH3)2) ppm. Anal. Calcd for C39H63AuBF4N2P: C, 53.55; H, 7.26; N, 3.20. Found: C, 53.52; H, 7.17; N, 3.28. Synthesis of [Au(IPr)(PnBu3)][BF4] (3ja0 ). The general procedure afforded 3ja0 as a white microcrystalline solid (130.6 mg, 90%). 1H NMR (400 MHz, CDCl3): δ 7.54 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.50 (d, J = 0.8 Hz, 2H, CH imidazole IPr), 7.32 (d, J = 7.8 Hz, 4H, CH aromatic IPr), 2.52 (sept, J = 6.7 Hz, 4H, CH(CH3)2),1.51-1.59 (m, 6H, nBu3P), 1.27 (d, J = 6.7 Hz, 12H, CH(CH3)2), 1.26 (d, J = 6.7 Hz, 12H, CH(CH3)2) 1.25-1.16 (m overlapping with previous signal, 6H, nBu3P), 1.09-0.98 (m, 6H, nBu3P), 0.78 (t, J = 7.3 Hz, 9H, nBu3P) ppm. 31 P NMR (162 Hz, CDCl3): δ 29.7 (s, nBu3P) ppm. 19F NMR (282 Hz, CDCl3): δ -158.4 (m, BF4) ppm. 13C NMR (75 MHz, CDCl3): δ 191.6 (d, J = 122.0 Hz, C carbene), 145.7 (s, C aromatic IPr), 133.2 (s, C aromatic IPr), 131.0 (s, CH aromatic IPr), 124.9 (d, J = 3.1 Hz, CH imidazole IPr), 124.2 (s, CH aromatic IPr), 28.7 (s, CH(CH3)2), 27.3 (s, CH2 nBu3P), 24.9 (d, J = 33.9 Hz, CH2 nBu3P), 24.8 (s, CH(CH3)2), 23.9 (d, J = 15.0 Hz, CH2 nBu3P), 23.9 (s, CH(CH3)2), 13.5 (s, CH3 nBu3P) ppm. Anal. Calcd for C39H63AuBF4N2P: C, 53.55; H, 7.26; N, 3.20. Found: C, 53.49; H, 7.10; N, 3.21. Synthesis of [Au(IPr)(PPh3)][BF4] (3ka0 ). The general procedure afforded 3ka0 as a white microcrystalline solid (140.6 mg, 91%). 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 0.8 Hz, 2H, CH imidazole IPr), 7.60 (t, J = 7.8 Hz, 2H, CH aromatic IPr), 7.53-7.47 (m, 3H, CH aromatic Ph3P), 7.37-7.31 (m, 10H, 4H CH aromatic IPr and 6H CH aromatic Ph3P), 7.01-6.94 (m, 6H CH aromatic Ph3P), 2.55 (sept, J = 6.7 Hz, 4H, CH(CH3)2), 1.27 (d, J = 13.7 Hz, 12H, C(CH3)3 Ph3P), 1.15 (d, J = 13.7 Hz, 12H, C(CH3)3 Ph3P) ppm. 31P (162 Hz, CDCl3): δ 40.0 (s, Ph3P) ppm. 19F NMR (282 Hz, CDCl3): δ -154.8 (m, BF4) ppm. 13C NMR (75 MHz, CDCl3): δ 188.2 (d, J = 126.4 Hz, C carbene), 145.8 (s, C aromatic IPr), 133.6 (d, J = 13.8 Hz, CH aromatic Ph3P), 133.2 (s, C aromatic IPr), 132.3 (d, J = 2.2 Hz, CH aromatic Ph3P), 131.1 (s, CH aromatic IPr), 129.4 (d, J = 11.7 Hz, CH aromatic Ph3P), 127.4 (d, J = 58.9 Hz, C aromatic Ph3P), 125.3 (d, J = 3.1 Hz, CH imidazole IPr), 124.3 (s, CH aromatic IPr), 28.8 (s, CH(CH3)2), 24.7 (s, CH(CH3)2), 23.9 (s, CH(CH3)2) ppm. Anal. Calcd for C45H51AuBF4N2P: C, 57.83; H, 5.50; N, 3.00. Found: C, 57.45; H, 5.28; N, 2.92.

Acknowledgment. Support of this work by the ERC (Advanced Researcher Grant to S.P.N.) and the EPSRC is gratefully acknowledged. The authors thank Professor Luigi Cavallo for helpful discussions and assistance with the SambVca calculations. S.P.N. is a Royal SocietyWolfson Research Merit Award holder. Supporting Information Available: This material is available free of charge via the Internet at http://pubs.acs.org.