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Organometallics 2009, 28, 2356–2359
Selective Platinum-Catalyzed C-F Bond Activation as a Route to Fluorinated Aryl Methyl Ethers Heather L. Buckley, Tongen Wang, Olivia Tran, and Jennifer A. Love* Department of Chemistry, 2036 Main Mall, UniVersity of British Columbia, VancouVer, British Columbia V6T 1Z1, Canada ReceiVed February 9, 2009 Summary: [(CH3)2Pt(µ-SMe2)]2catalyzes the formation of aryl methyl ethers Via selectiVe C-F bond actiVation of polyfluoroarylimines. This reaction is functional group tolerant and proceeds in good to excellent yields. The optimization and preliminary substrate scope of this process are described. The activation of strong carbon-element bonds remains a significant challenge in organometallic chemistry. In recent years, platinum-based complexes have shown increasing potential for selective carbon-atom bond activation. Detailed mechanistic investigations of these transformations have brought new understanding to the range of reactivity accessible. Significant advances in platinum chemistry include carbon-hydrogen1 and carbon-halogen bond activation,2 complexes of heavier element species,3 reductive elimination from both Pt(II)4 and Pt(IV) species,5 dehydrogenation,6 and a range of applications such as sensors for SO2 and other * To whom correspondence should be addressed. E-mail: jenlove@ chem.ubc.ca. (1) (a) Crespo, M. Organometallics 1995, 14, 355–364. (b) Wick, D. D.; Goldberg, K. I. J. Am. Chem. Soc. 1997, 119, 10235–10236. (c) Johansson, L.; Tilset, M.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2000, 122, 10846–10855. (d) Johansson, L.; Tilset, M. J. Am. Chem. Soc. 2001, 123, 739–740. (e) Johansson, L.; Tilset, M. J. Am. Chem. Soc. 2001, 123, 739– 740. (f) Zhong, H. A.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2002, 124, 1378–1399. (g) Heyduk, A. F.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2003, 125, 6366–6367. (h) Fekl, U.; Goldberg, K. I. J. Am. Chem. Soc. 2002, 124, 6804–6805. (i) Song, D.; Wang, S. Organometallics 2003, 22, 2187–2189. (j) Jensen, M. P.; Wick, D. D.; Reinartz, S.; White, P. S.; Templeton, J. L.; Goldberg, K. I. J. Am. Chem. Soc. 2003, 125, 8614–8624. (k) Iverson, C. N.; Carter, C. A. G.; Baker, T.; Scollard, J. D.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2003, 125, 12674–12675. (l) Plutino, M. R.; Scolaro, L. M.; Albinati, A.; Romeo, R. J. Am. Chem. Soc. 2004, 126, 6470–6484. (m) Ong, C. M.; Burchell, T. J.; Puddephatt, R. J. Organometallics 2004, 23, 1493–1495. (n) Heyduk, A. F.; Driver, T. G.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2004, 126, 15034–15035. (o) Zhao, S.-B.; Song, D.; Jia, W.-L.; Wang, S. Organometallics 2005, 24, 3290–3296. (p) Zhang, F.; Kirby, C. W.; Hairsine, D. W.; Jennings, M. C.; Puddephatt, R. J. J. Am. Chem. Soc. 2005, 127, 14196–14197. (q) Lersch, M.; Tilset, M. Chem. ReV. 2005, 105, 2471–2526. (r) Zhao, S.-B.; Wu, G.; Wang, S. Organometallics 2006, 25, 5979–5989. (s) Young, K. J. H.; Meier, S. K.; Gonzales, J. M.; Oxgaard, J.; Goddard, W. A., III; Periana, R. A. Organometallics 2006, 25, 4734– 4737. (t) Wik, B. J.; Lersch, M.; Krivokapic, A.; Tilset, M. J. Am. Chem. Soc. 2006, 128, 2682–2696. (u) Labinger, J. A.; Bercaw, J. E.; Tilset, M. Organometallics 2006, 25, 805–808. (v) Capape´, A.; Crespo, M.; Granell, J.; Vizcarro, A.; Zafrilla, J.; Font-Bardia, M.; Solans, X. Chem. Commun. 2006, 4128–4130. (w) Vedernikov, A. N. Curr. Org. Chem. 2007, 11, 1401– 1416. (x) Kloek, S. M.; Goldberg, K. I. J. Am. Chem. Soc. 2007, 129, 3460– 3461. (y) Driver, T. G.; Williams, T. J.; Labinger, J. A.; Bercaw, J. E. Organometallics 2007, 26, 294–301. (z) Chen, G.; Labinger, J. A.; Bercaw, J. E. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 6915–6920. (aa) Williams, T. J.; Caffyn, A. J. M.; Hazari, N.; Oblad, P. F.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2008, 130, 2418–2419. (2) (a) Crespo, M.; Martinez, M.; de Pablo, E. J. Chem. Soc., Dalton Trans. 1997, 1231–1235. (b) Rashidi, M.; Esmaeilbeig, A. R.; Shahabadi, N.; Tangestaninejad, S.; Puddephatt, R. J. J. Organomet. Chem. 1998, 568, 53–61. (c) Crespo, M.; Granell, J.; Solans, X.; Font-Bardia, M. Organometallics 2002, 21, 5140–5143. (d) Song, D.; Sliwowski, K.; Pang, J.; Wang, S. Organometallics 2002, 21, 4978–4983.
gases,7 biosensors,8 and photochemical products.9 Moreover, the use of Pt(II)/Pt(IV) redox cycles in catalysis is becoming increasingly common. In particular, we have been interested in using Pt(II) complexes to catalyze the activation and subsequent functionalization of aryl C-F bonds. Although several examples of stoichiometric1a,r,2b,10 and catalytic C-F activation have been reported,11 only limited examples for the catalytic cross-coupling of polyfluoroarenes have emerged.12 We recently reported that [(CH3)2Pt(µ-SMe2)]2 catalyzes the methylation of a wide range of fluorinated aryl (3) (a) Janzen, M. C.; Jennings, M. C.; Puddephatt, R. J. Organometallics 2001, 20, 4100–4106. (b) Janzen, M. C.; Jennings, M. C.; Puddephatt, R. J. Inorg. Chem. 2001, 40, 1728–1729. (c) Janzen, M. C.; Jennings, M. C.; Puddephatt, R. J. Inorg. Chem. 2003, 42, 4553–4558. (4) (a) Braterman, P. S.; Cross, R. J.; Young, G. B. J. Chem. Soc., Dalton Trans. 1976, 1892–1897. (b) Komiya, S.; Abe, Y.; Yamamoto, A.; Yamamoto, T. Organometallics 1983, 2, 1466–1468. (c) Schmidtberg, G. S.; Stapp, B.; Brune, H. A. J. Organomet. Chem. 1986, 307, 129–137. (d) Shekhar, S.; Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 13016–13027. (5) (a) Hill, G. S.; Puddephatt, R. J. Organometallics 1997, 16, 4522– 4524. (b) Williams, B. S.; Holland, A. W.; Goldberg, K. I. J. Am. Chem. Soc. 1999, 121, 252–253. (c) Williams, B. S.; Goldberg, K. I. J. Am. Chem. Soc. 2001, 123, 2576–2587. (d) Crumpton-Bregel, D. M.; Goldberg, K. I. J. Am. Chem. Soc. 2003, 125, 9442–9456. (e) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett. 2003, 5, 1055–1058. (f) Procelewska, J.; Zahl, A.; Liehr, G.; van Eldik, R.; Smythe, N. A.; Williams, B. S.; Goldberg, K. I. Inorg. Chem. 2005, 44, 7732–7742. (g) Khusnutdinova, J. R.; Zavalij, P. Y.; Vedernikov, A. N. Organometallics 2007, 26, 3466–3483. (h) Luedtke, A.; Goldberg, K. I. Inorg. Chem. 2007, 46, 8696–8698. (i) Pawilowski, A. V.; Getty, A. D.; Goldberg, K. I. J. Am. Chem. Soc. 2007, 129, 10382–10393. (j) Khusnutdinova, J. R.; Newman, L.; Zavalij, P. Y.; Lam, Y.-F.; Vedernikov, A. N. J. Am. Chem. Soc. 2008, 130, 2174–2175. (k) YahavLevi, A.; Goldberg, I.; Vigalok, A.; Vedernikov, A. N. J. Am. Chem. Soc. 2008, 130, 724–731. (l) Smythe, N. A.; Grice, K. A.; Williams, S.; Goldberg, K. I. Organometallics 2009, 28, 277–288. (6) (a) Khaskin, E.; Zavalij, P. Y.; Vedernikov, A. N. J. Am. Chem. Soc. 2006, 128, 13054–13055. (b) Fekl, U.; Kaminsky, W.; Goldberg, K. I. J. Am. Chem. Soc. 2003, 125, 15286–15287. (7) (a) Albrecht, M.; Gossage, R. A.; Spek, A. L.; van Koten, G. Chem. Commun. 1998, 1003–1004. (b) Albrecht, M.; Lutz, M.; Schreurs, A. M. M.; Lutz, E. T. H.; Spek, A. L.; van Koten, G. Dalton Trans. 2000, 3797– 3804. (c) Albrecht, M.; Lutz, M.; Spek, A. L.; van Koten, G. Nature (London) 2000, 406, 970–974. (d) Albrecht, M.; Gossage, R. A.; Lutz, M.; Spek, A. L.; van Koten, G. Chem. Eur. J. 2000, 6, 1431–1445. (e) Albrecht, M.; Gossage, R. A.; Frey, U.; Ehlers, A. W.; Baerends, E. J.; Merbach, A. E.; van Koten, G. Inorg. Chem. 2001, 40, 850–855. (f) Albrecht, M.; Schlupp, M.; Bargon, J.; van Koten, G. Chem. Commun. 2001, 1874–1875. (8) Albrecht, M.; Rodrı´guez, J.; Schoonmaker, J.; van Koten, G. Org. Lett. 2000, 2, 3461–3464. (9) (a) Song, D.; Wu, Q.; Hook, A.; Kozin, I.; Wang, S. Organometallics 2001, 20, 4683–4689. (b) Liu, Q.-D.; Jia, W.-L.; Wu, G.; Wang, S. Organometallics 2003, 22, 3781–3791. (c) Bai, D.-R.; Wang, S. Organometallics 2006, 25, 1517–1524. (10) (a) Crespo, M.; Martinez, M.; Sales, J. J. Chem. Soc., Chem. Commun. 1992, 822–823. (b) Anderson, C.; Crespo, M.; Ferguson, G.; Lough, A. J.; Puddephatt, R. J. Organometallics 1992, 11, 1177–1181. (c) Crespo, M.; Martinez, M.; Sales, J. Organometallics 1993, 12, 4297–4304. (d) Reinhold, M.; McGrady, J. E.; Perutz, R. N. J. Am. Chem. Soc. 2004, 126, 5268–5276. (e) 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. (f) Colmenares, F.; Torrens, H. J. Phys. Chem. A 2005, 109, 10587–10593.
10.1021/om900100f CCC: $40.75 2009 American Chemical Society Publication on Web 03/27/2009
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imines to generate unsymmetrical, functionalized aryl fluoride products that are not available by other processes (eq 1).13
Such functionalized organofluorine compounds have great potential for application in pharmaceutical14 and other industries; indeed, recent estimates suggest that up to 20% of new drugs and approximately 30% of new agrochemicals contain fluorine.15,16 The bioactivity of fluorine-containing organics is due in part to their unique properties, including solubility in a range of solvents, lipophilicity, high metabolic stability, and the ability to hydrogen bond. The low abundance of naturally occurring organofluorine compounds, as well as the limited range of readily available fluorinated building blocks, renders these molecules of great synthetic interest. Aryl ethers are another class of compounds that have inspired considerable synthetic efforts because of their prevalence in bioactive molecules17 and materials.18 They have also emerged recently as potential cross-coupling reagents.19 Historically, the (11) (a) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet. Chem. 1973, 50, C12. (b) Aizenberg, M.; Milstein, D. Science 1994, 265, 359–361. (c) Wilhelm, R.; Widdowson, D. A. J. Chem. Soc., Perkin Trans. 1 2000, 3808– 3813. (d) Bo¨hm, V. P. W.; Gsto¨ttmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387–3389. (e) Mongin, F.; Mojovic, L.; Guillamet, B.; Tre´court, F.; Que´guiner, G. J. Org. Chem. 2002, 67, 8991–8994. (f) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2003, 125, 5646–5647. (g) Kim, Y. M.; Yu, S. J. Am. Chem. Soc. 2003, 125, 1696–1697. (h) Mikami, K.; Miyamoto, T.; Hatano, M. Chem. Commun. 2004, 2082–2083. (i) Dankwardt, J. W. J. Organomet. Chem. 2005, 690, 932–938. (j) Liu, J.; Robins, M. J. Org. Lett. 2005, 7, 1149–1151. (k) Hazari, A.; Gouverneur, V.; Brown, J. M. Angew. Chem., Int. Ed. 2009, 48, 1296–1299. (12) (a) Edelbach, B. L.; Kraft, B. M.; Jones, W. D. J. Am. Chem. Soc. 1999, 121, 10327–10331. (b) Braun, T.; Perutz, R. N.; Sladek, M. I. Chem. Commun. 2001, 2254–2255. (c) Steffen, A.; Sladek, M. I.; Braun, T.; Neumann, B.; Stammler, H.-G. Organometallics 2005, 24, 4057–4064. (d) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 17978–17979. (e) Braun, T.; Izundu, J.; Steffen, A.; Neumann, B.; Stammler, H.-G. Dalton Trans. 2006, 5118–5123. (f) Schaub, T.; Backes, M.; Radius, U. J. Am. Chem. Soc. 2006, 128, 15964–15965. (g) Korn, T. J.; Schade, M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725–728. (h) Guo, H.; Kong, F.; Kanno, K.-I.; He, J.; Nakajima, K.; Takahashi, T. Organometallics 2006, 25, 2045–2048. (13) (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. (14) Ding, Y.-S.; Liu, N.; Wang, T.; Marecek, J.; Garza, V.; Ojima, I.; Fowler, J. S. Nucl. Med. Biol. 2000, 27, 381–389. (15) Kirk, K. L. Org. Process Res. DeV. 2008, 12, 305–321. (16) Mu¨ller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881–1886. (17) (a) Jung, M. E.; Rohloff, J. C. J. Org. Chem. 1985, 50, 4909– 4913. (b) Boger, D. L.; Yohannes, D. J. Org. Chem. 1989, 54, 2498–2502. (c) Boger, D. L.; Sakya, S. M.; Yohannes, D. J. Org. Chem. 1991, 56, 4204–4207. (d) Evans, D. A.; Wood, M. R.; Trotter, B. W.; Richardson, T. I.; Barrow, J. C.; Katz, J. K. Angew. Chem., Int. Ed. 1998, 37, 2700– 2704. (e) Evans, D. A.; Dinsmore, C. J.; Watson, P. S.; Wood, M. R.; Richardson, T. I.; Trotter, B. W.; Katz, J. L. Angew. Chem., Int. Ed. 1998, 37, 2704–2708. (f) Nicolaou, K. C.; Natarajan, S.; Li, H.; Jain, N. F.; Hughes, R.; Solomon, M. E.; Ramanjulu, J. M.; Boddy, C. N. C.; Takayanagi, M. Angew. Chem., Int. Ed. 1998, 37, 2708–2714. (g) Nicolaou, K. C.; Jain, N. F.; Natarajan, S.; Hughes, R.; Solomon, M. E.; Li, H.; Ramanjulu, J. M.; Takayanagi, M.; Koumbis, A. E.; Bando, T. Angew. Chem., Int. Ed. 1998, 37, 2714–2716. (h) Nicolaou, K. C.; Takayanagi, M.; Jain, N. F.; Natarajan, S.; Koumbis, A. E.; Bando, T.; Ramanjulu, J. M. Angew. Chem., Int. Ed. 1998, 37, 2717–2719. (i) Boger, D. L.; Miyazaki, S.; Kim, S. H.; Wu, J. H.; Loiseleur, O.; Castle, S. L. J. Am. Chem. Soc. 1999, 121, 3226–3227. (j) Deng, H.; Jung, J.-K.; Liu, T.; Kuntz, K. W.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 9032–9034. (18) (a) Cotter, R. J. In Engineering Plastics: A Handbook of Polyarylethers; Gordon and Breach: Langhorne, PA, 1995. (b) Hay, A. S. Prog. Polym. Sci. 1999, 24, 45–80. (19) Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem., Int. Ed. 2008, 47, 4866–4869.
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Ullmann coupling has seen extensive use in aryl ether synthesis,20 but harsh conditions and the need for excess Cu salt make new approaches desirable.21 Notably, Pd-catalyzed crosscoupling of alkoxides and phenoxides with aryl bromides has been advanced independently by both Hartwig and Buchwald as the first method of generating aryl ethers through a conventional cross-coupling cycle.22 Notwithstanding these significant contributions, methods to generate fluorinated aryl methyl ether building blocks, which could have considerable bioactivity, have not been reported. On the basis of our earlier work using [(CH3)2Pt(µ-SMe2)]2 for catalytic C-F activation,13 we have discovered that this complex also catalyzes aryl methyl ether formation. We disclose herein the development, optimization, and preliminary scope of this reaction. Anticipating that silanes should serve as excellent transmetalation reagents, we treated trifluoroaryl imine 1a with 5 mol % of [(CH3)2Pt(µ-SMe2)]2 and 1.2 equiv of tetramethoxysilane under typical cross-coupling conditions from our previous report on C-C bond formation (eq 2). These reactions were carried out on an appropriate scale (0.034 mmol of imine) to allow reaction monitoring by 1H and 19F NMR spectroscopy. A new product was generated that contained a distinctive singlet at approximately δ 3.9, indicative of incorporation of a methoxy substituent. The spectrum also showed a diagnostic imine CHN resonance at δ 8.6. After 24 h at 60 °C, 2a was obtained in 63% conversion as the sole product.
Our next task was to determine the necessity of the platinum catalyst, particularly as aryl ethers can be generated from fluoroaromatics through nucleophilic aromatic substitution (SNAr). To determine whether or not such a process could promote the conversion of 1a to 2a, the reaction of 1a under Table 1. Control Experiments That Exclude SNAr for Conversion of 1a to 2a
a
The byproduct appears to be an isomer of 1a (wherein the imine is conjugated to the unsubstituted aryl group), on the basis of 1H NMR and 19F NMR spectroscopy as well as LRMS. b Conversions based on 1 H NMR spectroscopy by integration of the CHN resonance, with 1,3,5-trimethoxybenzene as an internal standard. c Mixture of several byproducts apparent by 1H NMR spectroscopy.
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Table 2. Optimization of Conditions for C-O Cross-Coupling
entry
solvent
temp (°C)
silane (equiv)
conversn (%)a
1 2 3 4 5 6 7 8 9 10
CD3CN CD3CN d6-DMSO C6D6 CD2Cl2 CD2Cl2 CD2Cl2 CD2Cl2 THF THF
35 60 35 35 35 17 35 35 35 60
1.2 1.2 1.2 1.2 1.2 1.2 0.6 0.3 1.2 1.2
39 63 95 61
Table 3. Exploration of the Scope of Imines and Silanes for C-O Cross-Coupling
a Conversions based on 1H NMR spectroscopy by integration of the CHN proton resonance, with 1,3,5-trimethoxybenzene as an internal standard.
Pt-catalyzed conditions (Table 1, entry 1) was compared to standard SNAr conditions (entries 2-4).23 In THF at 60 °C, the Pt-catalyzed reaction proceeded to >95% conversion in 24 h. In marked contrast, the addition of excess sodium methoxide to a solution of 1a in CD2Cl2 generated only a trace amount of 2a (entry 2); similar results were found in THF. When methanol was added to the mixture (entry 3), 20% conversion to the aryl methyl ether 2a was observed after 24 h, with a further 20% conversion to multiple byproducts. The use of TBAF and tetramethoxysilane, which is an alternative method for SNAr, resulted exclusively in formation of what appears to be an isomer of 1a. We also discovered that added methoxide ion has a slightly deleterious effect on the catalytic reaction (entry 1 as compared to entry 5). These results clearly indicate that conventional SNAr conditions are inadequate for the efficient conversion of 1a to 2a. Moreover, there was no conversion when [(CH3)2Pt(µ-SMe2)]2 was omitted from the reaction of 1a with Si(OCH3)4 (entry 6). Having established that the platinum catalyst is required for the conversion of 1a to 2a, we next sought to optimize the reaction conditions for this process; results of this study are presented in Table 2. Although CD3CN was the optimal solvent for our previous C-C cross-coupling work, only moderate yields of product were obtained in the C-O bond forming reaction (entries 1 and 2). At the extremes of polarity, d6-DMSO (entry 3) and C6D6 (entry 4) gave poor yields, whereas high conversion was obtained with both CD2Cl2 (entry 5) and THF (entry 9) at 35 °C. Because our previous work13a had shown that a (20) Ullmann, F. Ber. Dtsch. Chem. Ges. 1904, 37, 853–854. (21) (a) Marcoux, J. F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 10539–10540. (b) Kalinin, A. V.; Bower, J. F.; Riebel, P.; Snieckus, V. J. Org. Chem. 1999, 64, 2986–2987. (c) Ouali, A.; Spindler, J.-F.; Christau, H.-J.; Taillefer, M. AdV. Synth. Catal. 2006, 348, 499–505. (d) Schmittling, E. A.; Sawyer, J. S. J. Org. Chem. 1993, 58, 3229–3230. (e) Sawyer, J. S.; Schmittling, E. A.; Palkowitz, J. A.; Smith, W. J., III J. Org. Chem. 1998, 63, 6338–6343. (f) Zhao, J. K.; Wang, Y. G. Chin. Chem. Lett. 2003, 14, 1012–1014. (g) Wang, T.; Love, J. A. Synthesis 2007, 2237– 2239. (22) (a) Mann, G.; Incarvito, C.; Rheingold, A. L.; Hartwig, J. F. J. Am. Chem. Soc. 1999, 121, 3224–3225. (b) Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 4369–4378. (c) Katoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67, 5553–5566. (d) Anderson, K. W.; Ikawa, T.; Tundel, R. E.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 10694–10695. (e) Tzschucke, C. C.; Murphy, J. M.; Hartwig, J. F. Org. Lett. 2007, 9, 761–764. (f) Altman, R. A.; Shafir, A.; Choi, A.; Lichtor, P. A.; Buchwald, S. L. J. Org. Chem. 2008, 73, 284–286. (23) (a) Idoux, J. P.; Gupton, J. T.; McCurry, C. K.; Crews, A. D.; Jurss, C. D.; Colon, C.; Rampi, R. C. J. Org. Chem. 1983, 48, 3771–3773. (b) Idoux, J. P.; Madenwald, M. L.; Garcia, B. S.; Chu, D. L.; Gupton, J. T. J. Org. Chem. 1985, 50, 1876–1878.
a Yields are based on 1H NMR spectroscopy by integration of the CHN resonance, with 1,3,5-trimethoxybenzene as an internal standard, and are averaged over several runs. b After chromatography, the corresponding aldehydes were isolated and characterized as products of these reactions. c Reaction run in CD3CN at 60 °C. d Product of C-C bond formation also observed (95% yield (entry 1). Other silanes also reacted with this imine to generate 2a (entries 2-4). The use of PhSi(OMe)3 generated 2a in 46% yield along with ca. 10% of the aryl methyl imine, resulting from stoichiometric coupling of one of the methyl groups from [(CH3)2Pt(µ-SMe2)]2. It is notable that competing incorporation of a phenyl group from PhSi(OMe)3 was not observed (entry 2). Reactions with (CH3)nSi(OMe)4-n successfully formed 2a, but in lower yields than that with Si(OMe)4 (entries 3 and 4). Consequently, Si(OMe)4 was used to investigate the imine scope. Reactions of several other imines with Si(OMe)4 generated moderate to excellent yields of the corresponding aryl methyl ether products (entries 5-7 and 9). The imine products characterized in situ are reported in Table 3. The imine products were prone to hydrolysis; thus, the corresponding aldehydes were isolated for characterization. A notable feature of this reaction is the tolerance for other potentially reactive functional groups remote from the ortho position. In no cases did we observe competing C-Br or C-Cl bond cleavage (entries 7-10), despite these being considerably weaker bonds and typically more susceptible to cross-coupling than aryl C-F bonds. The high selectivity is likely due to the imine directing group, consistent with our discovery that the same aryl fluorides undergo efficient methylation ortho to the imine.13a In cases where the conversion to product is low (e.g., entry 8), the remainder of the material was recovered as unreacted starting material. We are currently exploring the reaction mechanism and anticipate that this study will yield insight into the factors contributing to the incomplete conversions, as well as allowing a systematic extension of the substrate scope. Finally, the apparent requirement for a 2,4,6-substitution pattern on the aryl imine is also worthy of comment. Imine 1g (entry 10) underwent C-O bond formation in only 12% conversion, whereas 1h (entry 11) provided
