Copyright 2009
Volume 28, Number 3, February 9, 2009
American Chemical Society
Communications Oxidative Addition of Glycosylbromides to trans-Ir(PMe3)2(CO)Cl Elizabeth M. Pelczar, Colleen Munro-Leighton, and Michel R. Gagne´* UniVersity of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290 ReceiVed NoVember 22, 2008 Summary: trans-Ir(PMe3)2(CO)Cl reacts with acetobromo-RD-glucose in the presence of AIBN to giVe a 1.3:1 ratio of the retentiVe and inVertiVe oxidatiVe addition products, each of which were characterized by crystallography. Reaction with R-D-glucopyranosyl bromide tetrabenzoate gaVe a 2:1 R:β ratio, while acetobromo-R-D-mannose gaVe a 5:1 ratio of retentiVe to inVertiVe products. Although anomeric effects present a means to potentially control the stereochemistry of metal-catalyzed reactions occurring at the C1 carbon of sugars, few studies have addressed the question of how anomeric effects influence oxidative addition reactions at C1. In the case of glycosyl halide electrophiles it has, however, been demonstrated that clean invertive oxidative addition by anionic nucleophiles is possible when the reactions are fast (e.g., [Mn(CO)5-]1-3 or [CpFe(CO)2-]4). Sluggish reactions, however, are poorly selective, since halide byproducts initiate Lemieux anomerization processes that erode the stereospecificity.5 In addition * To whom correspondence should be addressed. E-mail: mgagne@ unc.edu. (1) DeShong, P.; Soli, E. D.; Slough, G. A.; Sidler, D. R.; Elango, V.; Rybczynski, P. J.; Vosejpka, L. J. S.; Lessen, T. A.; Le, T. X.; Anderson, G. B.; von Philipsborn, W.; Vo¨hler, M.; Rentsch, D.; Zerbe, O. J. Organomet. Chem. 2000, 593-594, 49–62. (2) DeShong, P.; Slough, G. A.; Sidler, D. R.; Elango, V.; Rybczynski, P. J.; Smith, L. J.; Lessen, T. A.; Le, T. X.; Andersen, G. B. In Cycloaddition Reactions in Carbohydrate Chemistry; American Chemical Society: Washington, DC, 1992; pp 97-111. (3) DeShong, P.; Slough, G. A.; Elango, V.; Trainor, G. L. J. Am. Chem. Soc. 1985, 107, 7788–7790. (4) Trainor, G. L.; Smart, B. E. J. Org. Chem. 1983, 48, 2447–2448. (5) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. J. Am. Chem. Soc. 1975, 97, 4056–4062.
to two-electron pathways, one-electron reducing agents such as (Cp2TiCl)26 and [Co(dmgH)2py-]7 can generate reactive C1 organometallic complexes, the latter species being observed as the R-glucoside with radical intermediates being implicated in their reactivities.8,9 The above stable organometallic complexes were characterized primarily by NMR methods that rely on vicinal H,H coupling constants along the sugar backbone to report on the chair conformation and anomer selectivity. We report herein the oxidative addition reactivity of Vaska’s complex with various glycosyl bromides and provide X-ray crystallographic data that directly report on the diastereoselectivity of oxidative addition at Ir(I) and additionally confirm previously employed NMR tools. Vaska’s complex, trans-Ir(PPh3)2(CO)Cl (1), has long been known to principally promote oxidative addition reactions via the two-electron pathway.10,11 In contrast the PMe3 derivative, trans-Ir(PMe3)2(CO)Cl (2), is more promiscuous in its choice of mechanism and often chooses radical pathways.12,13 These iridium complexes were therefore chosen as a starting point to study how anomeric effects influenced the mechanism of oxidative addition in sugar electrophiles. We report herein the results of these reactions as well as the solid-state crystal (6) Cavallaro, C. L.; Schwartz, J. J. Org. Chem. 1995, 60, 7055–7057. (7) Ghosez, A.; Goebel, T.; Giese, B. Chem. Ber. 1988, 121, 1807– 1811. (8) Dupuis, J.; Giese, B.; Hartung, J.; Leising, M.; Korth, H.-G.; Sustmann, R. J. Am. Chem. Soc. 1985, 107, 4332–4333. (9) Giese, B.; Dupuis, J. Angew. Chem., Int. Ed. 1983, 22, 622–623. (10) Vaska, L. J. Am. Chem. Soc. 1964, 86, 1943–1950. (11) Heck, R. F. J. Am. Chem. Soc. 1964, 86, 2796–2799. (12) Labinger, J. A.; Osborn, J. A. Inorg. Chem. 1980, 19, 3230–3236. (13) Labinger, J. A.; Osborn, J. A.; Coville, N. J. Inorg. Chem. 1980, 19, 3236–3243.
10.1021/om8011135 CCC: $40.75 2009 American Chemical Society Publication on Web 01/06/2009
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Figure 1. X-ray structure of trans-Ir(PMe3)2(CO)(Cl)(Br)(R-acetoglucopyranose).
structure of trans-Ir(PMe3)2(CO)(Cl)(Br)(R-acetoglucopyranose) and trans-Ir(PMe3)2(CO)(Cl)(Br)(β-acetoglucopyranose), which are, to the best of our knowledge, the first examples of crystallographically characterized C1-glycopyranosyl organometallic complexes. The reaction of acetobromo-R-D-glucose (3) with both 1 and 2 in benzene at 65 °C did not yield any oxidative addition product. Osborn has shown that the addition of AIBN (azobis(isobutyronitrile)) to the reaction of 1-bromo-2-phenylethane with 2 increased both the rate and yield of the reaction.13 Adding AIBN to the reaction of 1 and 3 had no effect, however, in the reaction of 2 and 3; the oxidative addition product was indeed formed, with a 1.3:1 preference for the R over the β anomer (eq 1), on the basis of 1H NMR analysis. In the 31P{1H} NMR these two diastereomers showed coincidental AB quartets. The excess glucosyl bromide and minor β anomer were easily removed with a diethyl ether wash of the crude material to yield the pure R anomer.
Communications
Figure 2. X-ray structure of trans-Ir(PMe3)2(CO)(Cl)(Br)(β-acetoglucopyranose). Scheme 1
the preferential equatorial orientation of the metal is supported by previous NMR analyses.1-7
The structure of trans-Ir(PMe3)2(CO)(Cl)(Br)(R-acetoglucopyranose) showed the iridium to be equatorial and each of the sugar substituents to be oriented axially (Figure 1).14 This arrangement was consistent with the solution structure deduced from the broadened singlets (small vicinal JH-H) of the ring protons (3-6 ppm) in the 1H NMR spectrum, which are indicative of equatorial-equatorial relationships between the vicinal hydrogens in an inverted chair. The all-axial OAc sugar results from a retentive oxidative addition and a chair flip to place the [Ir] in the more favorable equatorial position. The crystal structure also showed that the PMe3 groups remain trans and are characterized by two sets of doublets in the 1H NMR. The 31P{1H} NMR shows a characteristic AB quartet at -36.5 and -36.8 ppm (2JP-P ) 105 Hz). Although no other solidstate structures of glycosyl metal complexes have been reported, (14) Crystals showed some indication of satellite reflections, which could indicate an incommensurate structure. The structure also had a number of ill-defined thermal parameters, also consistent with an average structure. For the time being this has been handled by constraining thermal parameters to be similar to those of their nearest neighbors.
Crystals of the β anomer, the product of invertive oxidative addition, were grown from the diethyl ether wash. As in the R anomer, the square plane of the original trans-Ir(PMe3)2(CO)Cl complex remained intact with the Br- and glucosyl ring adding mutually trans (Figure 2). The structure additionally showed that the OAc protecting groups and [Ir] each orient equatorially, again consistent with the solution structure deduced from the 1 H NMR spectrum, where all but one of the resonances due to the ring protons were sharp with coupling constants between 9 and 13 Hz indicative of axial-axial vicinal H-H relationships. The 1H NMR also showed a sharp virtual triplet at 1.78 ppm (N ) 16 Hz), often observed for trans PMe3 groups.15 The 31 P{1H} NMR was characterized by an AB quartet at -35.5 and -37.8 ppm (2JP-P ) 792 Hz), with the upfield doublet slightly broadened.16
(15) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals; Wiley: New York, 1994. (16) Although the AB quartets for each anomer seem as though they should be resolved in the crude NMR, the main peaks of the minor β product overlap with the outside quartet signals of the major R product, leading to the appearance of a single product.
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Reaction of either R-D-glucopyranosyl bromide tetrabenzoate (4)17 or R-D-mannopyranosyl bromide tetraacetate (5) with 2 also gave the oxidative addition products (eqs 2 and 3); however, unlike the case with 3, the oxidative addition occurred in the absence of AIBN and its presence did not affect the rate, suggesting a different mechanism than above. In the case of 5, the AIBN reaction was messier.
In the reaction of 2 with 4, the R and β anomers were formed in a 1.8:1 ratio on the basis of 1H NMR analysis. The mixture of both anomers showed broadened singlets for the major R anomer and smaller sharper signals for the β species. The 31 P{1H} NMR showed two sets of AB quartets that overlapped in their upfield doublets. The reaction with 5 also showed broad signals in the 1H NMR due to the R anomer and sharper signals due to the β anomer. The 31P{1H} NMR showed two easily discernible sets of AB quartets which integrated to 5.1:1. The C1-H and C2-H protons of the major R isomer were coincidentally overlapped, which precluded the observation of the key axial-axial vicinal coupling constant. The AB quartet belonging to the β product resonates at -40.3 and -43.1 ppm (2JP-P ) 349 Hz). The β products are the result of oxidative additions to the Ir(I) that are invertive at C1 and trans at Ir. Since the reaction of 2 with 3 required AIBN to proceed, one reasonably invokes radical intermediates in the process. One such mechanism, a radical chain variant, is shown in Scheme 1. The mechanism invokes an initiative Br• abstraction to generate a glucosyl radical8,9,18,19 that attacks Ir(I) to generate an intermediate glucosyl-Ir(II) species that subsequently propagates the chain (17) In the reaction of trans-Ir(PPh3)2(CO)Cl and 3, with or without AIBN, and 4, with AIBN, multiple products were observed in the 31P{1H} NMR. Reaction with 4 in the absence of AIBN only returned starting material. (18) Adlington, R. M.; Baldwin, J. E.; Basak, A.; Kozyrod, R. P. J. Chem. Soc., Chem. Commun. 1983, 944–945. (19) Dupuis, J.; Giese, B.; Ru¨egge, D.; Fischer, H.; Korth, H.-G.; Sustmann, R. Angew. Chem., Int. Ed. 1984, 23, 896–898.
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by abstracting Br• from 3. Arguing against various single electron transfer (SET) mechanisms or direct Br• abstraction by Ir(I) is the lack of reactivity in the absence of AIBN.15 The stereochemistry of oxidative addition should be established in the glucose radical + Ir(I) step of the propagation.20 Worth noting here is that the glucose-free radical is a ground-state boat that tends to react with alkenes with high R selectivities8,9,18 and metal radicals such as SmI2 with β selectivities.21,22 Unlike the acetoxy-protected glucosides, SET initiated processes or Br• abstraction by Ir(I)15 may be operating in 4 or 5, which did not require AIBN initiation. Despite these potentially different mechanisms, the diastereoselectivities were not found to be significantly different, ranging from 1.3:1 to ∼5:1 for retentive oxidative addition, the latter for the manno sugar.23 In summary, we have reported on the oxidative addition reactions of acetobromo-R-D-glucose (3), R-D-glucopyranosyl bromide tetrabenzoate (4), and acetobromo-R-D-mannose (5) to trans-Ir(PMe3)2(CO)Cl. In all three cases the reaction favored the R anomer by a net retentive oxidative addition. The reactions of 4 and 5 with trans-Ir(PMe3)2(CO)Cl occurred with or without AIBN and with the same dr value. In the case of 3, the reaction with trans-Ir(PMe3)2(CO)Cl proceeded only with AIBN, suggestive of a radical chain mechanism. In no case did transIr(PPh3)2(CO)Cl lead to a successful oxidative addition. In addition, trans-[Ir(PMe3)2(CO)(Cl)(Br)(R-acetoglucopyranose)] and trans-[Ir(PMe3)2(CO)(Cl)(Br)(β-acetoglucopyranose)] were each characterized by single-crystal X-ray methods, which confirmed the NMR analyses used to assign anomer configuration and the chair form of the pyranoside ring.
Acknowledgment. We thank the Department of Energy, Office of Basic Energy Sciences, for funding (Grant No. FG02-05ER15630). Supporting Information Available: Text, figures, and tables giving full experimental details and characterization data for new compounds and CIF files giving X-ray data for trans-Ir(PMe3)2(CO)(Cl)(Br)(R-acetoglucopyranose) and transIr(PMe3)2(CO)(Cl)(Br)(β-acetoglucopyranose). This material is available free of charge via the Internet at http://pubs.acs.org. OM8011135 (20) The observed selectivities appear to be kinetic on the basis of the following control experiments. (1) Thermolysis of an epimerically pure trans-Ir(PMe3)2(CO)(Cl)(Br)(R-acetoglucopyranose) at 65 °C (16 h) did not erode the dr; (2) spiking the reaction in eq 1 with trans-Ir(PMe3)2(CO)(Cl)(Βr)(Racetoglucopyranose) yielded a product mixture whose dr was that expected from a sum of the expected 1.7:1 R:β and the spiked pure R. This latter control showed that radicals, AIBN, and putative odd-electron intermediates do not erode the product dr. (21) Hung, S.-C.; Wong, C.-H. Angew. Chem., Int. Ed. 1996, 35, 2671– 2674. (22) Miquel, N.; Doisneau, G.; Beau, J.-M. Angew. Chem., Int. Ed. 2000, 39, 4111–4114. (23) While the role of anomeric effects is a bit blurred by the diverging behavior noted above, cyclohexyl bromide was found to be completely unreactive under the free radical initiation conditions, pointing to a significant reactivity benefit if not a stereochemical one.
