Flexible, Bowl-Shaped N-Heterocyclic Carbene ... - ACS Publications

Organometallics 2009, 28, 465–472

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Flexible, Bowl-Shaped N-Heterocyclic Carbene Ligands: Substrate Specificity in Iridium-Catalyzed Ketone Hydrosilylation Anthony R. Chianese,* Allen Mo, and Dibyadeep Datta Department of Chemistry, Colgate UniVersity, 13 Oak DriVe, Hamilton, New York 13346 ReceiVed September 9, 2008

A series of benzimidazolium chlorides was synthesized as precursors to N-heterocyclic carbene ligands, with N-substituents varying in size from 3,5-xylyl (1a) to first-generation dendritic 3,5-bis(3,5-di-tertbutylphenyl)phenyl (1b), to the second-generation 3,5-bis[3,5-bis(3,5-di-tert-butylphenyl)phenyl]phenyl (1c). The dendritic side groups of 1b and 1c form a flexible, bowl-like cavity. Iridium complexes of 1a-c were synthesized and were shown to be catalytically active for the hydrosilylation of aryl methyl ketones. The dendritic ligands 1b and 1c effect a moderate level of substrate specificity in the competitive hydrosilylation of ketones of varying size. In the competitive hydrosilylation of acetophenone versus 3-(3,5-di-tert-butylphenyl)acetophenone, acetophenone is consumed approximately 3.7 times more quickly using the second-generation ligand 1c. Using the control ligand 1a, this ratio is 1.8. Introduction A central goal in synthetic chemistry is the development of organic transformations that are simultaneously general and specific. The most widely useful methods offer predictable selectivity for a well-defined class of substrates, ideally tolerating variations in substrate auxiliary functionality and steric size. Homogeneous catalysis is at the center of this effort, as rational and empirical variation of the catalyst structure provides a versatile, cost-effective manifold for optimizing the reaction outcome. Enzymes are known for their often extreme substrate specificity, but Nature has also evolved catalysts with synthetically useful generality, as evidenced by the utility of lipases in kinetic resolutions.1 Efforts at bridging the gap between traditional synthetic catalysis and the exquisite, superstructure-directed selectivity exhibited by enzymes are challenging, but many successes2 motivate continued study. For example, Nolte et al.,3 Gibson and Rebek,4 and Crabtree, Brudvig, et al.5 have observed substrate recognition in transition metal catalysis using rationally designed, host-like ligands. Breit and co-workers6-8 and Reek and co-workers9 have employed recognition in ligand selfassembly. Nguyen, Hupp, et al.10 and Wa¨rnmark et al.11 have employed self-assembled catalysts for specificity, while Ray* To whom correspondence should be addressed. E-mail: achianese@ colgate.edu. (1) Turner, N. J. Curr. Opin. Chem. Biol. 2004, 8, 114–119. (2) Das, S.; Brudvig, G. W.; Crabtree, R. H. Chem. Commun. 2008, 413–424. (3) Coolen, H. K. A. C.; Meeuwis, J. A. M.; Van Leeuwen, P. W. M. N.; Nolte, R. J. M. J. Am. Chem. Soc. 1995, 117, 11906–11913. (4) Gibson, C.; Rebek, J. Org. Lett. 2002, 4, 1887–1890. (5) Das, S.; Incarvito, C. D.; Crabtree, R. H.; Brudvig, G. W. Science 2006, 312, 1941–1943. (6) Weis, M.; Waloch, C.; Seiche, W.; Breit, B. J. Am. Chem. Soc. 2006, 128, 4188–4189. (7) Breit, B.; Seiche, W. Angew. Chem., Int. Ed. 2005, 44, 1640–1643. (8) Breit, B.; Seiche, W. J. Am. Chem. Soc. 2003, 125, 6608–6609. (9) Kuil, M.; Soltner, T.; van Leeuwen, P.; Reek, J. N. H. J. Am. Chem. Soc. 2006, 128, 11344–11345. (10) Merlau, M. L.; Mejia, M. D. P.; Nguyen, S. T.; Hupp, J. T. Angew. Chem., Int. Ed. 2001, 40, 4239–4242. (11) Jo´nsson, S.; Odille, F. G. J.; Norrby, P. O.; Wa¨rnmark, K. Chem. Commun. 2005, 549–551.

mond, Bergman, et al.12,13 have demonstrated selective catalysis inside enclosed self-assembled containers. Mirkin and coworkers14,15 have designed allosterically regulated catalysts. One strategy that mimics some features of enzyme catalysis is to enclose a catalyst in the core of a dendrimer.16-22 With higher generations, the reaction microenvironment is defined increasingly by the dendrimer structure rather than the solvent. Interesting and potentially useful effects have been observed, including increased catalyst activity,23,24 varied selectivity,25-27 and substrate specificity.28,29 This report describes the synthesis of dendritic N-heterocyclic carbene (NHC)30 ligands expected to exhibit a bowl-like topology and their application to iridium-catalyzed ketone hydrosilylation, with an emphasis on discrimination between (12) Fiedler, D.; Leung, D. H.; Bergman, R. G.; Raymond, K. N. Acc. Chem. Res. 2005, 38, 349–358. (13) Fiedler, D.; Bergman, R. G.; Raymond, K. N. Angew. Chem., Int. Ed. 2004, 43, 6748–6751. (14) Gianneschi, N. C.; Nguyen, S. T.; Mirkin, C. A. J. Am. Chem. Soc. 2005, 127, 1644–1645. (15) Gianneschi, N. C.; Bertin, P. A.; Nguyen, S. T.; Mirkin, C. A.; Zakharov, L. N.; Rheingold, A. L. J. Am. Chem. Soc. 2003, 125, 10508– 10509. (16) Brunner, H. J. Organomet. Chem. 1995, 500, 39–46. (17) Smith, D. K.; Diederich, F. Chem.-Eur. J. 1998, 4, 1353–1361. (18) Astruc, D.; Chardac, F. Chem. ReV. 2001, 101, 2991–3023. (19) Oosterom, G. E.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. Angew. Chem., Int. Ed. 2001, 40, 1828–1849. (20) Twyman, L. J.; King, A. S. H.; Martin, I. K. Chem. Soc. ReV. 2002, 31, 69–82. (21) Helms, B.; Fre´chet, J. M. J. AdV. Synth. Catal. 2006, 348, 1125– 1148. (22) Me´ry, D.; Astruc, D. Coord. Chem. ReV. 2006, 250, 1965–1979. (23) Fujihara, T.; Obora, Y.; Tokunaga, M.; Sato, H.; Tsuji, Y. Chem. Commun. 2005, 4526–4528. (24) Mu¨ller, C.; Ackerman, L. J.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2004, 126, 14960–14963. (25) Ooe, M.; Murata, M.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126, 1604–1605. (26) Oosterom, G. E.; van Haaren, R. J.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. Chem. Commun. 1999, 1119–1120. (27) Sato, H.; Fujihara, T.; Obora, Y.; Tokunaga, M.; Kiyosu, J.; Tsuji, Y. Chem. Commun. 2007, 269–271. (28) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708–5711. (29) Chow, H. F.; Mak, C. C. J. Org. Chem. 1997, 62, 5116–5127. (30) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290–1309.

10.1021/om800878m CCC: $40.75  2009 American Chemical Society Publication on Web 12/19/2008

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Figure 1. N-Heterocyclic carbene ligands with m-phenylene dendritic side groups.

aryl methyl ketone substrates of varying size. Substrate specificity has been explored using competition experiments continuously monitored by NMR spectroscopy. The largest ligand employed, 1c, exhibits modest specificity for smaller ketone substrates over larger ones, as compared to smaller control ligands 1a and 1b. The smallest and largest iridium-NHC precatalysts have been structurally characterized by X-ray crystallography.

Results and Discussion Ligand Design and Synthesis. Inspection of molecular models indicates that for NHC ligands with dendritic side groups based on a 1,3,5-substituted aromatic monomer unit as shown in Figure 1, the carbene lone pair (or bound metal atom) rests at the bottom of a roughly bowl-shaped cavity. The structure may be highly rigid or semiflexible, depending on hindrance of rotation about the aryl-aryl linkages. Goto and Kawashima have used the same meta-terphenyl framework in the synthesis of bowl-shaped tertiary phosphine ligands, which have an extremely large cone angle, estimated at 206°.31,32 Tsuji and (31) Ohzu, Y.; Goto, K.; Kawashima, T. Angew. Chem., Int. Ed. 2003, 42, 5714–5717. (32) Ohzu, Y.; Goto, K.; Sato, H.; Kawashima, T. J. Organomet. Chem. 2005, 690, 4175–4183.

co-workers have employed phosphine ligands of this nature in palladium-catalyzed Suzuki-Miyaura coupling33 and rhodiumcatalyzed ketone hydrosilylation. A significant rate enhancement was observed for the latter reaction, caused by enhanced formation of monophosphine-rhodium species.34,35 Ding and coworkers have shown that achiral bowl-shaped phosphine ligands are also useful for Ru-catalyzed asymmetric hydrogenation of ketones.36 Goto and Kawashima have also reported the synthesis of an NHC with meta-terphenyl side groups; a derived Pd0 complex exhibited unique reactivity toward CO2 and O2.37 Benzimidazolium precursors to 1a-c were synthesized as shown in Scheme 1. The simplest ligand precursor, 1a · HCl, was prepared via Buchwald-Hartwig amination38,39 of 1,2(33) Ohta, H.; Tokunaga, M.; Obora, Y.; Iwai, T.; Iwasawa, T.; Fujihara, T.; Tsuji, Y. Org. Lett. 2007, 9, 89–92. (34) Niyomura, O.; Iwasawa, T.; Sawada, N.; Tokunaga, M.; Obora, Y.; Tsuji, Y. Organometallics 2005, 24, 3468–3475. (35) Niyomura, O.; Tokunaga, M.; Obora, Y.; Iwasawa, T.; Tsuji, Y. Angew. Chem., Int. Ed. 2003, 42, 1287–1289. (36) Jing, Q.; Zhang, X.; Sun, H.; Ding, K. L. AdV. Synth. Catal. 2005, 347, 1193–1197. (37) Yamashita, M.; Goto, K.; Kawashima, T. J. Am. Chem. Soc. 2005, 127, 7294–7295. (38) Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, 5575–5580. (39) Sadighi, J. P.; Harris, M. C.; Buchwald, S. L. Tetrahedron Lett. 1998, 39, 5327–5330.

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Scheme 1. Synthesis of Benzimidazolium Salts 1a-c · HCl43

dibromobenzene with 3,5-dimethylaniline to give 3, followed by treatment with triethyl orthoformate and HCl.40 To prepare the first-generation dendrimer 1b · HCl, nitroarene 4 was synthesized by the Suzuki coupling41 of 3,5-di-tert-butylbenzeneboronic acid with 3,5-dibromonitrobenzene. Reduction of the nitro group42 then gave the aniline 5, from which benzimidazolium salt 1b · HCl was acquired analogously to 1a · HCl. To synthesize the second-generation 1c · HCl, Suginome’s procedure for boronic acid masking was employed.44 First, 3,5dibromobenzeneboronic acid was protected with 1,8-diaminonaphthalene to give 6. Reaction with 3,5-di-tert-butylbenzeneboronic acid under Buchwald’s optimized conditions for Suzuki (40) Khramov, D. M.; Boydston, A. J.; Bielawski, C. W. Org. Lett. 2006, 8, 1831–1834. (41) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew. Chem., Int. Ed. 2004, 43, 1871–1876. (42) McDonald, I. M.; Black, J. W.; Buck, I. M.; Dunstone, D. J.; Griffin, E. P.; Harper, E. A.; Hull, R. A. D.; Kalindjian, S. B.; Lilley, E. J.; Linney, I. D.; Pether, M. J.; Roberts, S. P.; Shaxted, M. E.; Spencer, J.; Steel, K. I. M.; Sykes, D. A.; Walker, M. K.; Watt, G. F.; Wright, L.; Wright, P. T.; Xun, W. J. Med. Chem. 2007, 50, 3101–3112.

coupling41 gave 7 in high yield, and deprotection with aqueous acid in THF44 yielded boronic acid 8. Coupling with 3,5dibromonitrobenzene gave 9, and nitro-group reduction gave 10. Palladium-catalyzed amination of 1,2-dibromobenzene followed by treatment with triethyl orthoformate and HCl then gave the desired benzimidazolium chloride 1c · HCl. Synthesis and Characterization of Iridium Complexes. Neutral iridium(I) complexes of ligands 1a-c were synthesized by Lin’s method45 of transmetalation from intermediate silver(I) complexes 1a-c · AgCl (Scheme 2). Metalation of the benzimidazolium salts 1a-c · HCl using Ag2O was monitored by 1 H NMR spectroscopy, but the silver complexes were not isolated as described by Lin and co-workers. Instead, [Ir(cod)Cl]2 (cod ) 1,5-cyclooctadiene) was added directly to the dichlo(43) Abbreviations: rac-BINAP ) rac-2,2′-bis(diphenylphosphino)-1,1′binaphthyl; SPHOS ) 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl; DPEPHOS ) bis(2-diphenylphosphinophenyl) ether. (44) Noguchi, H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc. 2007, 129, 758–759. (45) Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972–975.

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Scheme 2. Synthesis of Iridium Complexes 2a-c

romethane solutions of 1a-c · AgCl. Precipitation of silver chloride was observed immediately, but the mixtures were allowed to stir at room temperature for 30 min before workup. Iridium complexes 2a-c were isolated by silica gel chromatography in 36-58% yield. The 1H and 13C NMR spectra for 2a-c are as expected for complexes of the general formula Ir(NHC)(cod)Cl.46-50 Cyclooctadiene vinylic hydrogens appear in the range 2.50-2.74 ppm for the alkene moiety trans to chloride; those trans to the NHC ligand appear at 4.49-4.61 ppm, indicative of the larger trans influence of the NHC ligand. The carbene carbon resonates at 192.0-193.3 ppm. For 2a, the four methyl groups are chemically equivalent by 1H and 13C NMR; the same is true for the ortho-CH groups and the meta-ipso carbons. This indicates that rotation about the N-C single bonds is fast on the NMR time scale. For 2b and 2c, a broadened resonance is observed for the four hydrogens closest to the benzimidazole ring in the 1H NMR spectrum; the associated carbon signal is also broad in the 13C NMR spectrum. This is consistent with rotation about the N-C bonds near the fast exchange limit. Complexes 2a and 2c were structurally characterized by X-ray crystallography. Figure 2 shows the structure of 2a. Figure 3 shows the full structure of 2c, and Figure 4 shows a close-up view of the organometallic fragment. Relevant distances and angles are given in Table 1 (2a) and Table 2 (2c). The structural parameters for 2a and 2c are consistent with previously characterized related complexes.47,51,52 The Ir-CNHC distances of 2.007 Å (2a) and 2.008 Å (2c) are within the expected range. The unsymmetrical binding of cyclooctadiene reflects the larger trans influence of the NHC ligand as compared to chloride: the distance between Ir and the alkene centroid trans to the NHC ligand is 2.063 Å for 2a and 2.063 for 2c, while the distance to the alkene centroid trans to chloride is 1.981 Å for 2a and 1.995 for 2c. As is generally observed for monodentate NHC ligands, the benzimidazol-2-ylidine ring plane is orthogonal to the iridium coordination plane. The crystal structure of 2c confirms what is predicted by molecular models: that NHC ligand 1c forms a loose pocket around the iridium center, which is expected to impose an (46) Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus, G. R. J. Chem.-Eur. J. 1996, 2, 772–780. (47) Chianese, A. R.; Li, X. W.; Janzen, M. C.; Faller, J. W.; Crabtree, R. H. Organometallics 2003, 22, 1663–1667. (48) Stylianides, N.; Danopoulos, A. A.; Tsoureas, N. J. Organomet. Chem. 2005, 690, 5948–5958. (49) Kelly, R. A.; Clavier, H.; Giudice, S.; Scott, N. M.; Stevens, E. D.; Bordner, J.; Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P. Organometallics 2008, 27, 202–210. (50) Zanardi, A.; Peris, E.; Mata, J. A. New J. Chem. 2008, 32, 120– 126. (51) Seo, H.; Kim, B. Y.; Lee, J. H.; Park, H. J.; Son, S. U.; Chung, Y. K. Organometallics 2003, 22, 4783–4791. (52) Herrmann, W. A.; Baskakov, D.; Herdtweck, E.; Hoffmann, S. D.; Bunlaksananusorn, T.; Rampf, F.; Rodefeld, L. Organometallics 2006, 25, 2449–2456.

Figure 2. ORTEP diagram of 2a, showing 50% probability ellipsoids. Hydrogen atoms are omitted for clarity.

Figure 3. ORTEP diagram of 2c, showing 50% probability ellipsoids. Hydrogen atoms are omitted for clarity.

Figure 4. ORTEP diagram of 2c, showing 50% probability ellipsoids. Side groups attached to C(81) and C(123) are excluded, and hydrogen atoms are omitted for clarity.

energetic cost as the side groups rearrange to accommodate a large incoming substrate. Ketone Hydrosilylation. The hydrosilylation of carbonyl compounds to give silyl ethers is a useful transformation, as

Flexible, Bowl-Shaped NHC Ligands

Organometallics, Vol. 28, No. 2, 2009 469 Table 1. Selected Bond Lengths and Angles for 2a Bond Lengths (Å)

Ir(1)sC(1) Ir(1)sCl(1) Ir(1)sC(24)

2.007(4) 2.384(1) 2.101(4)

N(1)sC(1)sN(2) N(1)sC(1)sIr(1)

105.2(3) 126.1(3)

Ir(1)sC(25) Ir(1)sC(28) Ir(1)sC(29)

2.106(4) 2.189(5) 2.165(5)

N(2)sC(1)sIr(1) C(1)sIr(1)sCl(1)

128.5(3) 92.65(10)

Bond Angles (deg)

Torsion Angles (deg) -92.2(3) 93.7(3)

N(1)sC(1)sIr(1)sCl(1) N(2)sC(1)sIr(1)sCl(1)

Table 2. Selected Bond Lengths and Angles for 2c Bond Lengths (Å) Ir(1)sC(1) Ir(1)sCl(1) Ir(1)sC(74)

2.008(3) 2.3654(8) 2.169(3)

N(1)sC(1)sN(2) N(1)sC(1)sIr(1)

105.4(2) 127.20(19)

Ir(1)sC(75) Ir(1)sC(78) Ir(1)sC(79)

2.179(4) 2.108(4) 2.124(3)

N(2)sC(1)sIr(1) C(1)sIr(1)sCl(1)

127.3(2) 92.20(8)

Bond Angles (deg)

Torsion Angles (deg) -96.1(2) 87.5(2)

N(1)sC(1)sIr(1)sCl(1) N(2)sC(1)sIr(1)sCl(1)

protected alcohols can be produced directly from ketone or aldehyde precursors. Catalyst systems employing a wide variety of transition metal complexes have been developed, including several highly enantioselective systems for the asymmetric reduction of prochiral ketones.53,54 Rhodium complexes are often employed, but the use of less expensive iridium is increasingly common,55-62 inonecasegivingusefullydistinctenantioselectivity.63,64 Rhodium and iridium complexes of N-heterocyclic carbenes are well known as catalysts for ketone hydrosilylation,23,60,65-78 so this reaction is a potentially useful testbed for comparing the steric influence of ligands 1a-c in catalysis. Iridium complexes 2a-c proved to be active precatalysts for the hydrosilylation of aryl methyl ketones using diphenylsilane at room temperature. Hydrosilylation of acetophenone 11a, performed in benzene-d6 with 3.0 equiv of silane and 3 mol % catalyst, reaches full conversion in 3-17 h, depending on the ligand (Table 3). In each case, the major product is the silyl ether 12a, while 4% of the enol silyl ether 13a, a product of dehydrogenative silylation, is formed. A slight decrease in the yield (NMR) of 12a with increasing size of the NHC ligand is observed. To assess whether ligands that form a bowl-shaped cavity such as 1b and 1c can promote substrate specificity based on size and shape, the series of aryl methyl ketones shown in Figure (53) Diez-Gonzalez, S.; Nolan, S. P. Org. Prep. Proced. Int. 2007, 39, 523–559. (54) Carpentier, J. F.; Bette, V. Curr. Org. Chem. 2002, 6, 913–936. (55) Kinting, A.; Kreuzfeld, H. J.; Abicht, H. P. J. Organomet. Chem. 1989, 370, 343–349. (56) Faller, J. W.; Chase, K. J. Organometallics 1994, 13, 989–992. (57) Nishibayashi, Y.; Singh, J. D.; Segawa, K.; Fukuzawa, S.; Uemura, S. J. Chem. Soc., Chem. Commun. 1994, 1375–1376. (58) Nishibayashi, Y.; Segawa, K.; Singh, J. D.; Fukuzawa, S.; Ohe, K.; Uemura, S. Organometallics 1996, 15, 370–379. (59) Karame, I.; Tommasino, M. L.; Lemaire, M. J. Mol. Catal. A: Chem. 2003, 196, 137–143. (60) Chianese, A. R.; Crabtree, R. H. Organometallics 2005, 24, 4432– 4436. (61) Cuervo, D.; Dı´ez, J.; Gamasa, M. P.; Gimeno, J.; Paredes, P. Eur. J. Inorg. Chem. 2006, 599–608. (62) Go´mez, M.; Jansat, S.; Muller, G.; Bonnet, M. C.; Breuzard, J. A. J.; Lemaire, M. J. Organomet. Chem. 2002, 659, 186–195. (63) Nishibayashi, Y.; Segawa, K.; Ohe, K.; Uemura, S. Organometallics 1995, 14, 5486–5487. (64) Nishibayashi, Y.; Segawa, K.; Takada, H.; Ohe, K.; Uemura, S. Chem. Commun. 1996, 847–848.

Table 3. Hydrosilylation of Acetophenone Using Catalysts 2a-ca

entry

catalyst

time (h)

NMR yield 12a

NMR yield 13a

1 2 3

2a 2b 2c

3 16 17

92% 87% 84%

4% 4% 4%

a Initial concentration: 0.074 M 11a in benzene-d6. Yields calculated by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard.

5 was employed. Internal competition experiments were performed for each catalyst 2a-c, comparing the reactivity of acetophenone (11a) with larger ketones 11b-d of varying size and shape. For each experiment, the conversion of both substrates was monitored continuously by 1H NMR. For each catalyst and pair of substrates, Figure 6 shows the ratio of (65) Lappert, M. F.; Maskell, R. K. J. Organomet. Chem. 1984, 264, 217–28. (66) Herrmann, W. A.; Goossen, L. J.; Ko¨cher, C.; Artus, G. R. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 2805–2807. (67) Enders, D.; Gielen, H.; Breuer, K. Tetrahedron: Asymmetry 1997, 8, 3571–3574. (68) Enders, D.; Gielen, H.; Runsink, J.; Breuer, K.; Brode, S.; Boehn, K. Eur. J. Inorg. Chem. 1998, 913–919. (69) Duan, W. L.; Shi, M.; Rong, G. B. Chem. Commun. 2003, 2916– 2917. (70) Rivera, G.; Crabtree, R. H. J. Mol. Catal. A: Chem. 2004, 222, 59–73. (71) Cesar, V.; Bellemin-Laponnaz, S.; Wadepohl, H.; Gade, L. H. Chem.-Eur. J. 2005, 11, 2862–2873. ¨ ezdemir, I.; C¸etinkaya, B.; C¸etinkaya, E. J. Mol. Catal. (72) Yig˘it, M.; O A: Chem. 2005, 241, 88–92. (73) Yuan, Y.; Raabe, G.; Bolm, C. J. Organomet. Chem. 2005, 690, 5747–5752. (74) Chen, T.; Liu, X. G.; Shi, M. Tetrahedron 2007, 63, 4874–4880. ¨ zdemir, I.; Yig˘it, M.; Yig˘it, B.; C¸etinkaya, B.; C¸etinkaya, E. J. (75) O Coord. Chem. 2007, 60, 2377–2384. (76) Sato, H.; Fujihara, T.; Obora, Y.; Tokunaga, M.; Kiyosu, J.; Tsuji, Y. Chem. Commun. 2007, 269–271. (77) Wolf, J.; Labande, A.; Daran, J. C.; Poli, R. Eur. J. Inorg. Chem. 2007, 5069–5079. (78) Nonnenmacher, M.; Kunz, D.; Rominger, F. Organometallics 2008, 27, 1561–1568.

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effects a moderate level of substrate specificity in the competitive hydrosilylation of ketones of varying size and shape. Current efforts are directed at the development of ligands with conformationally more rigid dendritic side groups, which may improve the level of discrimination between substrates or between different carbonyl groups in the same substrate molecule.

Figure 5. Aryl methyl ketones of varying size and shape.

Experimental Section

A series of benzimidazole-based N-heterocyclic carbene ligands was synthesized as the hydrochloride salts, with Nsubstituents varying in size from a simple 3,5-xylyl group to first- and second-generation meta-phenylene-linked dendrimers that form a flexible, bowl-like cavity. Iridium complexes were synthesized and were shown to be catalytically active for the hydrosilylation of aryl methyl ketones. The largest ligand, 1c,

General Methods. [Ir(cod)Cl]2 was prepared as previously described.80 All other materials were commercially available and were used as received, unless otherwise noted. All solvents were reagent grade. Synthesis was performed using solvents that were sparged with argon, then passed through columns of activated alumina. Catalytic experiments were performed in benzene-d6, which was dried over activated 3.5 Å molecular sieves, but was not purified further. Isolated yields are given for all products. NMR spectra were recorded on a Bruker spectrometer operating at 400 MHz (1H NMR) and 100 MHz (13C NMR) and referenced to the residual solvent resonance (δ in parts per million, and J in Hz). NMR spectra were recorded at room temperature. Elemental analyses were performed by Robertson Microlit, Madison, NJ. Iridium Complex 2a. Benzimidazolium salt 1a · HCl (160 mg, 0.44 mmol) and Ag2O (56 mg, 0.24 mmol) were combined in a 25 mL Schlenk flask, and 10 mL of dry, degassed dichloromethane was added under argon. After stirring for 30 min, the flask was opened, and [Ir(cod)Cl]2 (147 mg, 0.22 mmol) was added. The mixture was stirred for an additional 30 min, opened, and filtered through Celite, washing with dichloromethane. The crude product was purified by flash chromatography on silica gel, first washing with dichloromethane, then eluting the product with 1:1 ethyl acetate/dichloromethane. The product was recrystallized from CH2Cl2/pentane. Yield: 170 mg, 58%. 1H NMR (CDCl3): δ 7.69 (s, 4H); 7.35 (AA′BB′, 2H, 3JHH ) 6.2 Hz, 4JHH ) 3.3 Hz); 7.23 (AA′BB′, 2H, 3JHH ) 6.2 Hz, 4JHH ) 3.3); 7.14 (s, 2H); 4.49 (m, 2H); 2.50 (m, 2H); 2.46 (s, 12H); 1.74 (m, 2H); 1.45 (m, 4H); 1.25 (m, 2H). 13C NMR (CDCl3): δ 192.0; 138.6; 137.6; 135.7; 130.0; 125.3; 123.2; 111.2; 84.7; 52.1; 33.1; 29.2; 21.5. Anal. Calcd for C31H34ClIrN2: C, 56.22; H, 5.17; N, 4.23. Found: C, 56.22; H, 5.18; N, 4.20. Iridium Complex 2b. Benzimidazolium salt 1b · HCl (0.146 mmol, 150 mg) and Ag2O (0.081 mmol, 18.8 mg) were combined in a 25 mL Schlenk flask, and 4 mL of dry, degassed dichloromethane was added under argon. After stirring for 30 min, the flask was opened, and [Ir(cod)Cl]2 (0.073 mmol, 48.8 mg) was added; a white precipitate was observed immediately. The mixture was stirred for an additional 30 min and then filtered through Celite. The solvent was evaporated, and the residue was purified by flash chromatography on silica gel, using 2% EtOAc in hexanes as eluent. The product was recrystallized by slow evaporation of a CH2Cl2/ benzene solution. Yield: 72 mg, 36%. 1H NMR (CDCl3): δ 8.33 (4H, br s), δ 8.03 (2H, s), δ 7.70 (8H, s), δ 7.52 (6H, m), δ 7.32 (2H, aa′bb′, 3JHH ) 6.1 Hz, 4JHH ) 3.2 Hz), δ 4.58 (2H, m), δ 2.6 (2H,m), δ 1.43 (72H, s), δ 1.66-1.16 (8H, m). 13C NMR (CDCl3): 193.3, 151.7, 143.6, 139.9, 138.3, 135.9, 126.6, 125.6, 123.5, 122.1, 122.1, 111.1, 85.8, 52.7, 35.3, 33.1, 31.7, 29.2. The coincidence at 122.1 ppm was verified by HMQC. Anal. Calcd for C83H106ClIrN2: C, 73.33; H, 7.86; N, 2.06. Found: C, 73.27; H, 8.01; N, 1.96. Iridium Complex 2c. Compound 1c · HCl (77.2 µmol) was dissolved in 5 mL of CH2Cl2, and silver(I) oxide (18 mg, 77 µmol) was added. The mixture was stirred under argon for 1 h, and [Ir(cod)Cl]2 (26 mg, 39 µmol) was added. After stirring for 30 min, the mixture was filtered through Celite. The volatiles were removed, and the residue was purified by flash chroma-

(79) See Supporting Information for conversion data at additional timepoints and additional time course plots.

(80) Lin, Y.; Nomiya, K.; Finke, R. G. Inorg. Chem. 1993, 32, 6040– 6045.

Figure 6. Results of internal competitive hydrosilylation of 11a versus 11b-d.The ratio of conversion 11a/11b-d is reported at 25% conversion of 11a.

conversion 11a/11b-d, when 11a is 25% consumed.79 As one might expect, no discrimination is observed between 11a and 11b using any catalyst, the only difference being the para tertbutyl group of 11b. For the competitive hydrosilylation of 11a versus 11c, which has a large 3,5-di-tert-butylphenyl group at the para position, catalyst 2c exhibits a slight discrimination, while catalysts 2a and 2b still show none. For 11a versus 11d, where the bulky di-tert-butylphenyl group is installed at the meta position, the unsubstituted 11a is consumed more rapidly using any catalyst, but the second-generation catalyst 2c shows the largest effect, as 11a is consumed approximately 3.7 times more quickly than 11d. Figure 7 shows the time course of competition experiments between 11a and 11d.79 It is apparent that both substrates are smoothly consumed throughout the course of the experiment and that the discrimination between 11a and 11d increases as the size of the NHC ligand is increased. It is also noteworthy that catalyst initiation and/or decomposition do not appear to pose a problem under these conditions.

Conclusion

Flexible, Bowl-Shaped NHC Ligands

Organometallics, Vol. 28, No. 2, 2009 471

Figure 7. Time course for competition experiments between substrate 11a and 11d. tography on silica gel, eluting with 1% ethyl acetate in hexanes. Some residual hexane was observed even after several days under vacuum at room temperature. Yield: 82 mg, 44%. 1H NMR (CDCl3): δ 8.51 (br d, 4H); 8.19 (br t, 2H); 7.95 (d, 8H, 4JHH ) 1.3 Hz); 7.81 (t, 4H, 4JHH ) 1.3 Hz); 7.58 (aa′bb′, 2H, 3JHH ) 6.1 Hz, 4JHH ) 3.2 Hz); 7.52 (d, 16H, 4JHH ) 1.6 Hz); 7.48 (t, 8H, 4JHH ) 1.6 Hz); 7.29 (aa′bb′, 2H, 3JHH ) 6.1 Hz, 4JHH ) 3.2 Hz); 4.61 (m, 2H, CHcod); 2.74 (m, 2H, CHcod); 1.7-1.25 (m, 8H, CH2-cod); 1.38 (s, 144H). 13C NMR (CDCl3): δ 193.2, 151.4, 144.2, 143.0, 141.2, 140.9, 138.9, 135.9, 127.2, 126.9, 125.8, 125.6, 123.6, 122.2, 121.9, 111.2, 86.2, 52.9, 35.2, 31.7, 29.9, 22.8. Anal. Calcd for C163H202ClIrN2: C, 81.00; H, 8.42; N, 1.16. Found: C, 80.88; H, 8.40; N, 1.09. X-ray Structure Determination of 2a. A yellow plate, obtained by slow evaporation of a dichloromethane/pentane solution, was mounted on a Cryoloop with Paratone oil and transferred to a Bruker CCD platform diffractometer. Unit cell determination, data collection, and multiscan absorption correction were performed using the APEX2 program suite. Subsequent calculations were carried out using the SHELXTL81 program package. The structure was solved by a Patterson projection and refined on F2 by full-matrix least-squares techniques. All non-hydrogen atoms were refined anisotropically, and hydrogen atoms were placed in calculated positions using a riding model. Details of data collection and refinement are given in Table 4. X-ray Structure Determination of 2c. A yellow plate, grown by slow evaporation of an ethanol/diethyl ether solution, was mounted on a Cryoloop with Paratone oil and transferred to a Bruker CCD platform diffractometer. Unit cell determination, data collection, and multiscan absorption correction were performed using the APEX2 program suite. Subsequent calculations were carried out using the SHELXTL81 program package. The structure was solved by direct methods (SHELXS) and refined on F2 by full-matrix least-squares techniques (SHELXL). In the main residue, a tert-butyl group was disordered over two conformations, C(8A)-C(12A) and C(8B)-C(12B); these fragments were restrained using SAME and were refined isotropically. Two diethyl ether molecules were located and included in the model. Correction for residual density of additional disordered solvent was performed using the option SQUEEZE in the program package PLATON.82 A total of 79 electrons per unit cell were removed, from a total potential solvent-accessible void of 1441.2 Å3. In the final Fourier difference map, a positive residual density peak of 5.35 e/Å3 was observed, 1.295 Å from C(78), 1.224 Å from C(79), and 2.135 Å from Ir(1). Attempts to account for this density were unsuccessful. All remaining nonhydrogen atoms were refined anisotropically, and hydrogen atoms were placed in calculated positions using a riding model. Details of data collection and refinement are given in Table 4. (81) Sheldrick, G. M. SHELXTL, Version 6.14; Bruker AXS Inc.: Madison, WI, 2004. (82) Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7–13.

Table 4. Crystal Data and Structure Refinement for 2a and 2c 2a color, shape empirical formula fw radiation temp (K) cryst syst space group unit cell dimens a (Å) b (Å) c (Å) R (deg) β (deg) χ (deg) V (Å3) Z Dcalc (g cm-3) µ(Mo KR) (mm-1) cryst size (mm) θ range for data coll. (deg) total, unique no. of reflns Rint no. of params, restraints R, Rw2 for all data R, Rw2 for I > 2σ GOF resid density (e Å-3)

2c

yellow, block C31H34ClIrN2 662.25 Mo KR, 0.71073 100 triclinic P1j (No. 2)

yellow, block C171H222ClIrN2O2 2565.32 Mo KR, 0.71073 100 triclinic P1j (No. 2)

7.9618(18) 11.220(3) 16.253(4) 81.661(3) 83.367(3) 70.772(3) 1352.9(6) 2 1.626 5.055 0.30 × 0.20 × 0.20 1.93 < θ < 28.76 9466, 6156 0.339 321, 0 0.0334, 0.0799 0.0312, 0.0780 1.074 -2.66 < 1.73

20.670(2) 21.111(2) 21.924(2) 105.182(1) 91.662(1) 112.457(1) 8442.8(14) 2 1.009 0.852 0.54 × 0.51 × 0.33 1.55 < θ < 28.36 121 184, 38 383 0.483 1645, 64 0.0619, 0.1358 0.0492, 0.1293 1.079 -0.80 < 5.35

Ketone Hydrosilylation, Table 3. Iridium complex 2a, 2b, or 2c (1.1 µmol) and 1,3,5-trimethoxybenzene (internal standard, 3.1 mg, 18.6 µmol) were weighed into a small vial. C6D6 (0.48 mL) was added, followed by diphenylsilane (21 µL, 0.112 mmol) and acetophenone (4.3 µL, 37.2 µmol). The tube was capped and inverted several times, and the reaction was monitored by 1 H NMR spectroscopy until acetophenone was fully consumed. The yield of silyl ether 12a was calculated by comparing the integration values of the CH3 doublet and the CH quartet with that of the OCH3 singlet from the internal standard, 1,3,5trimethoxybenzene. The yield of the enol silyl ether 13a was calculated by comparing the integration values of the two vinylic CH doublets with that of the OCH3 singlet from the internal standard, 1,3,5-trimethoxybenzene. Competition Experiments, Table 4. Iridium complex 2a, 2b, or 2c (1.1 µmol) and 1,3,5-trimethoxybenzene (internal standard, 3.1 mg, 18.6 µmol) were weighed into a small vial. About 0.3 mL of C6D6 was added, followed by diphenylsilane (69 µL, 0.372 mmol). The solution was transferred to an NMR tube, and C6D6 was added to bring the total volume to 0.5 mL. The tube was capped and incubated at room temperature for 2 h, during which time a small amount of H2 was evolved as adventitious water was consumed by iridium-catalyzed silane hydrolysis.83 Acetophenone (11a) and ketone 11b, 11c, and 11d were added (37.2 µmol of each), the NMR tube was inverted several times, and the reaction was monitored by 1H NMR at 23 °C for ap-

472 Organometallics, Vol. 28, No. 2, 2009 proximately 12 h. Conversion of the starting ketones was measured using the -COCH3 resonance. In all experiments, silyl ethers 12a-d were the major products; less than 5% yield (NMR) of silyl enol ether from dehydrogenative silylation was observed. Products 12a-d decompose upon attempts at chromatographic purification and were identified by their 1H NMR spectra, as observed in individual (noncompetition) hydrosilylation experiments using 2a as catalyst. The identities of silyl ethers 12c,d were confirmed by hydrolysis of the siloxy group and full characterization of the resulting alcohols 13c,d, as described in the Supporting Information. Silyl ethers 12a,b were identified by hydrolysis and comparison with the known phenethyl alcohols.84

Acknowledgment. This work was supported by generous funding from the ACS Petroleum Research Fund (46754GB3) and Colgate University. The authors would like to thank Bruce Foxman, Paul Williard, and James Golen for

Chianese et al.

helpful advice on X-ray crystallography, and the Crystallography Summer School hosted by Arnold Rheingold for instruction and use of instrumentation. Supporting Information Available: Details of the synthesis and characterization of new compounds, including images of 1 H and 13C NMR spectra. Complete data for catalytic experiments. CIF files giving X-ray diffraction data, atomic coordinates, thermal parameters, and complete bond distances and angles. This material is available free of charge via the Internet at http://pubs.acs.org. OM800878M

(83) Lee, Y.; Seomoon, D.; Kim, S.; Han, H.; Chang, S.; Lee, P. H. J. Org. Chem. 2004, 69, 1741–1743. (84) Hu, A. G.; Ngo, H. L.; Lin, W. B. J. Am. Chem. Soc. 2003, 125, 11490–11491.