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Organometallics 2009, 28, 6622–6624 DOI: 10.1021/om9008229
User-Friendly Precatalyst for the Methylation of Polyfluoroaryl Imines Heather L. Buckley, Alex D. Sun, and Jennifer A. Love* Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, British Columbia, V6T 1Z1, Canada Received September 21, 2009 Summary: A readily accessible, user-friendly Pt(II) complex (Cl2Pt(SMe2)2, 2) shows good reactivity for selective, catalytic methylation of polyfluoroarylimines.
Introduction The activation of carbon-fluorine bonds by transition metals has received considerable attention in recent years.1 Recent efforts have culminated in the emergence of both metal- and Lewis acid-catalyzed transformations,2-4 including work from our own laboratories, demonstrating the first examples of platinum-catalyzed C-F bond activation.4 This provides access to functionalized fluoroaromatics, which are of interest due to their potential for use as precursors to pharmaceuticals and novel materials. Specifically, our group has demonstrated that [(CH3)2Pt (μ-SMe2)]2 (1) is an effective precatalyst for the methylation of a range of polyfluoroaryl imines (eq 1).4a,b While the synthesis of 1 is reasonably straightforward, this complex is quite sensitive to air, water, and heat.5 We thus mobilized an effort to discover more user-friendly precatalysts with greater air, water, and thermal stability compared to 1.
*Corresponding author. E-mail:
[email protected]. (1) (a) Kiplinger, J. L.; Richmond, T. G.; Osterberg, C. E. Chem. Rev. 1994, 94, 373–431. (b) Braun, T.; Perutz, R. N. Chem. Commun. 2002, 2749–2757. (c) Lucht, B. L.; Poss, M. J.; King, M. A.; Richmond, T. G. J. Chem. Soc., Chem. Commun. 1991, 400–401. Crespo, M.; Martinez, M.; de Pablo, E. J. Chem. Soc., Dalton Trans. 1997, 1231–1235. (d) Anderson, C.; Crespo, M.; Ferguson, G.; Lough, A. J.; Puddephatt, R. J. Organometallics 1992, 11, 1177–1181. (e) Crespo, M.; Martinez, M.; Sales, J. Organometallics 1993, 12, 4297–4304. (f) Crespo, M. Organometallics 1995, 14, 355–364. (g) Reinhold, M.; McGrady, J. E.; Perutz, R. N. J. Am. Chem. Soc. 2004, 126, 5268–5276. (h) Jasim, N. A.; Perutz, R. N.; Whitwood, A. C.; Braun, T.; Izundu, J.; Neumann, B.; Rothfeld, S.; Stammler, H.-G. Organometallics 2004, 23, 6140–6149. (i) Ackermann, L.; Born, R.; Spatz, J. H.; Meyer, D. Angew. Chem., Int. Ed. 2005, 44, 7216–7219. (j) Garratt, S. A.; Hughes, R. P.; Kovacik, I.; Ward, A. J.; Willemsen, S.; Zhang, D. J. Am. Chem. Soc. 2005, 127, 15585–15594. (k) Hughes, R. P.; Larichev, R. B.; Zakharov, L. N.; Rheingold, A. L. Organometallics 2006, 25, 3943–3947. (l) Anderson, D. J.; McDonald, R.; Cowie, M. Angew. Chem., Int. Ed. 2007, 46, 3741–3744. (m) Schaub, T.; Fischer, P.; Steffen, A.; Braun, T.; Radius, U.; Mix, A. J. Am. Chem. Soc. 2008, 130, 9304–9317. (n) Erhardt, S.; Macgregor, S. A. J. Am. Chem. Soc. 2008, 130, 15490– 15498. (o) Nova, A.; Erhardt, S.; Jasim, N. A.; Perutz, R. N.; Macgregor, S. A.; McGrady, J. E.; Whitwood, A. C. J. Am. Chem. Soc. 2008, 130, 15499–15511. (p) Johnson, S. A.; Huff, C. W.; Mustafa, F.; Saliba, M. J. Am. Chem. Soc. 2008, 130, 17278–17280. (q) Johnson, S. A.; Taylor, E. T.; Cruise, S. J. Organometallics 2009, 28, 3842–3855. (r) Doster, M. E.; Johnson, S. A. Angew. Chem., Int. Ed. 2009, 48, 2185–2187. pubs.acs.org/Organometallics
Published on Web 11/09/2009
Of particular merit would be the ability to generate an active methylation catalyst in situ, which would obviate the need to isolate and store complex 1. Considering that [(CH3)2Pt(μ-SMe2)]2 (1) is prepared by the reaction of Cl2Pt(SMe2)2 (2) and methyllithium, we hypothesized that dimethylzinc, the transmetalation reagent of choice for the catalytic methylation, could be used to generate 1 (or a comparable catalytically active species) from 2 under catalytic reaction conditions. The practical advantages of such a process are considerable. PtCl 2(SMe2)2 is a yellow solid that is readily prepared5 in 88% yield from K2[PtCl4] and can be stored for months under air at ambient conditions. In comparison, the preparation of [(CH3)2Pt (μ-SMe2)]2 entails an additional step, involves lowtemperature recrystallization, and requires storage under nitrogen at -35 °C. Even with proper handling, [(CH3)2Pt(μ-SMe2)]2 has a tendency to degrade over time. As such, we sought to test complex 2 as an alternative precatalyst (2) For recent reviews and commentary, see: (a) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119–2183. (b) Perutz, R. N. Science 2008, 321, 1168–1169. (c) Meier, G.; Braun, T. Angew. Chem., Int. Ed. 2009, 48, 1546– 1548. (3) (a) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet. Chem. 1973, 50, C12. (b) Aizenberg, M.; Milstein, D. Science 1994, 265, 359–361. (c) Edelbach, B. L.; Kraft, B. M.; Jones, W. D. J. Am. Chem. Soc. 1999, 121, 10327–10331. (d) Wilhelm, R.; Widdowson, D. A. J. Chem. Soc., Perkin Trans. 1 2000, 3808–3813. (e) B€ohm, V. P. W.; Gst€ottmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387– 3389. (f) Braun, T.; Perutz, R. N.; Sladek, M. I. Chem. Commun. 2001, 2254–2255. (g) Mongin, F.; Mojovic, L.; Guillamet, B.; Trecourt, F.; Queguiner, G. J. Org. Chem. 2002, 67, 8991–8994. (h) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2003, 125, 5646–5647. (i) Kim, Y. M.; Yu, S. J. Am. Chem. Soc. 2003, 125, 1696–1697. (j) Mikami, K.; Miyamoto, T.; Hatano, M. Chem. Commun. 2004, 2082–2083. (k) Dankwardt, J. W. J. Organomet. Chem. 2005, 690, 932–938. (l) Liu, J.; Robins, M. J. Org. Lett. 2005, 7, 1149–1151. (m) Steffen, A.; Sladek, M. I.; Braun, T.; Neumann, B.; Stammler, H.-G. Organometallics 2005, 24, 4057–4064. (n) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 17978–17979. (o) Schaub, T.; Backes, M.; Radius, U. J. Am. Chem. Soc. 2006, 128, 15964–15965. (p) Braun, T.; Izundu, J.; Steffen, A.; Neumann, B.; Stammler, H.-G. Dalton Trans. 2006, 5118–5123. (q) Korn, T. J.; Schade, M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725–728. (r) Guo, H.; Kong, F.; Kanno, K.-I.; He, J.; Nakajima, K.; Takahashi, T. Organometallics 2006, 25, 2045–2048. (s) Panisch, R.; Bolte, M.; M€uller, T. J. Am. Chem. Soc. 2006, 128, 9676–9682. (t) Ozerov, O. V.; Douvris, C. Science 2008, 321, 1188–1190. (u) Reade, S. P.; Mahon, M. F.; Whittlesey, M. K. J. Am. Chem. Soc. 2009, 131, 1847–1861. (v) Hazari, A.; Gouverneur, V.; Brown, J. M. Angew. Chem., Int. Ed. 2009, 48, 1296–1299. (w) Braun, T.; Salomon, M. A.; Altenh€oner, K.; Teltewskoi, M.; Hinz, S. Angew. Chem., Int. Ed. 2009, 48, 1818–1822. (x) Wang, J.-R.; Manabe, K. Org. Lett. 2009, 11, 741–744. (y) Manabe, K.; Ishikawa, S. Synthesis 2008, 2645–2649. (z) Ishikawa, S.; Manabe, K. Synthesis 2008, 3180–3182. (4) (a) Wang, T.; Alfonso, B. J.; Love, J. A. Org. Lett. 2007, 9, 5629– 5631. (b) Wang, T.; Love, J. A. Organometallics 2008, 27, 3290–3296. (c) Buckley, H. L.; Wang, T.; Tran, O.; Love, J. A. Organometallics 2009, 28, 2356–2359. (5) Hill, G. S.; Irwin, M. J.; Levy, C. J.; Rendina, L. M.; Puddephatt, R. J.; Andersen, R. A.; McLean, L. Inorg. Synth. 1998, 32, 149–151. r 2009 American Chemical Society
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for catalytic C-F activation and cross-coupling of polyfluoroarylimines.
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Table 1. Comparison of in Situ and Isolated Precatalysts in Methylation
Results and Discussion To test the hypothesis that complex 2 could serve as a precatalyst under catalytic conditions, imine 3a (0.034 mmol) was dissolved in CD 3 CN (1 mL) and transferred to an NMR tube. Cl 2 Pt(SMe 2 )2 (0.0034 mmol, 10 mol %), dimethylzinc (0.041 mmol, 1.2 equiv), and 1,3,5-trimethoxybenzene (internal standard) were added sequentially, and the tube was heated at 60 °C (eq 2). Reaction progress was monitored periodically by 1 H and 19 F NMR spectroscopy. During the course of the reaction, resonances in the 1 H NMR spectrum consistent with the formation of Pt-CH 3 bonds were observed, on the basis of the characteristic chemical shifts (δ 0.5-1) and J Pt-H coupling constants (70-80 Hz). This result supports our hypothesis that 2 would react with dimethylzinc to generate a methyl platinum species. After 24 h, the reaction of 3a to 4a had proceeded cleanly in 60% yield, with the mass balance being unconverted starting material. No further progress was observed with prolonged heating. In comparison, complex 1 (5 mol % of the dimer) provides 4a in 95% yield. Comparable results are obtained if Cl 2 Pt(SMe 2 )2 is permitted to react for 6 h with dimethylzinc prior to addition of imine (eq 3). Thus, complex 2 is successful as a methylation precatalyst.
Encouraged by this promising result, we were prompted to investigate the substrate scope. Reactions of imines 3b-i were carried out as described for 3a. Table 1 shows the yields of reactions where the catalyst is generated in situ from Cl2Pt(SMe2)2, as well as a comparison to the yields obtained in reactions with [(CH3)2Pt(μ-SMe2)]2.4a In several cases where yields obtained with Cl2Pt(SMe2)2 are not as high as with [(CH3)2Pt(μ-SMe2)]2, Cl2Pt(SMe2)2 was pretreated with dimethylzinc for 6 h (entries 1, 7-9). Importantly, spectroscopic data for known compounds (entries 1-6, 8, and 9) matched the characterization data obtained in our earlier work.4a In general, the functional group tolerance of this reaction is high, with both nitriles and potentially reactive halogens being well-tolerated. In all cases except for imines 3c and 3f (entries 3 and 6), the yields are lower than those obtained with complex 1. However, comparable yields are obtained when complex 2 is pretreated with dimethylzinc for 6 h before addition of the imine. This suggests that the catalytic species is formed in situ. The ease of utility and thus convenience of complex 2 warrants its closer examination in catalysis. For imine 3c, the higher yield makes the new
a Yields based on 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. bTaken from ref 4a, unless otherwise noted. c Reactions run for 4-12 h at 60 °C, using 5 mol % [(CH3)2Pt(μ-SMe2)]2 and 0.6 equiv of ZnMe2; isolated yields reported unless otherwise indicated. d This paper; 71% isolated yield. eUnidentified byproducts were formed.
catalyst a better choice even without premixing; when run on a preparative scale, this reaction generated imine 4c in 97% isolated yield. Imines 3e-g (entries 5-7, respectively) react exclusively at the more substituted position, consistent with our previous results4a,b as well as stoichiometric C-F activation.1e Imine 3g (entry 7), which possesses a CF3 group ortho to the imine, had not been evaluated in our previous study. It is noteworthy that 3g is the first successful methylation substrate that does not possess a 2,6-difluoro substitution pattern. Moreover, the reaction of 3g demonstrates the selectivity of the C-F activation, with a preference for aryl over alkyl fluorides. The imine substituent of 3h, which possesses an aryl C-Cl bond, could potentially undergo C-Cl activation; however, only C-F activation is observed. This result is consistent with similar findings by Crespo and Martinez in stoichiometric C-F activation.1e The selectivity of this process could be attributable to faster reaction at the more electron-deficient ring, as well as a more facile formation of an unsaturated metallacycle.1e
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Having established the feasibility of using 2 as a methylation precatalyst, we turned our attention to stoichiometric experiments designed to probe the nature of the catalytic species being generated in situ. Unlike complex 1, which readily promotes stoichiometric C-F activation of 3a, no reaction was observed between complex 2 and 3a. In comparison, addition of 2.4 equiv of dimethylzinc to a mixture of complex 2 and 3a resulted in formation of 4a. Use of only 1.2 equiv of dimethylzinc was ineffective at promoting methylation. This result indicates that 2 equiv of methyl reagent are required, consistent with in situ generation of 1 from 2. These preliminary mechanistic studies support our hypothesis that the reaction of 2 with dimethylzinc generates a methyl platinum species capable of both stoichiometric and catalytic C-F activation reaction. This hypothesis is further supported by the appearance of characteristic Pt-CH3 peaks in the 1 H NMR spectrum upon mixing of 2 and dimethylzinc, although we cannot rigorously exclude other possible explanations at this time.
Conclusion In summary, we have shown that pretreatment of Cl2Pt(SMe2)2 with Me2Zn for 6 h, followed by addition of the appropriate imine, generates a species in situ that is as effective as [(CH3)2Pt(μ-SMe2)]2 at catalyzing methylation of a series of fluoroaryl imines. In some cases, pregeneration of the catalytic species is not needed. The use of Cl2Pt(SMe2)2 provides a practical alternative to other platinum species previously used for this chemistry. Mechanistic studies are underway to determine the exact nature of the catalytically active species.
Experimental Section General Procedures. Manipulation of organometallic compounds was performed using standard Schlenk techniques under an atmosphere of dry nitrogen or in a nitrogen-filled Vacuum Atmospheres drybox (O2
