Organometallics 2010, 29, 4203–4206 DOI: 10.1021/om100649z
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Dearomatization and C-H Deprotonation with Heavier Group 2 Alkyls: Does Size Matter? Merle Arrowsmith, Michael S. Hill,* and Gabriele Kociok-K€ ohn Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, U.K. Received July 5, 2010 Summary: We report that reaction of group 2 dialkyl compounds, [M{CH(SiMe3)2}2(THF)n] [M = Mg, Ca, n = 2; M = Sr, Ba, n = 3] with a bis(imino)pyridine ligand ultimately results in deprotonation of both methyl groups attached to the imine carbon center. The resulting compounds are mononuclear for M = Mg or Ca, but assemble into cyclic hexameric arrays when M = Sr or Ba. In all four cases deprotonation appears to occur by a common pathway involving pyridine dearomatization and subsequent deprotonation of a single imine-bound methyl substituent. Monitoring of each reaction has revealed that the efficacy of the transformation, as well as the stability of each intermediate, is dependent upon the identity, ionic radius, and resultant charge density of the alkaline earth reagent employed. The deprotonation and selective metalation of organic substrates is one of the main uses of organometallic derivatives of the s-block metals.1 While lithium and, to a lesser extent, magnesium compounds are likely to maintain their pre-eminence as the organic chemist’s reagents of choice, there is a growing awareness that either greater selectivity or deprotonating power may be achieved through the use of reagents containing heavier elements from groups 1 and 2 of the periodic table. While there have been rapid advances in related applications of multicomponent and mixed metal bases,2 our primary interest lies in the development of a more widespread stoichiometric and catalytic reaction chemistry based upon combinations of σ-bond metathesis and polarized insertion pathways for the heavier members of group 2, Ca, Sr, and Ba.3 Polarized metathesis reactivity without adjustment to the metal oxidation state is especially prevalent for electrophilic d0 and d0fn complexes of the early transition elements and lanthanides in their highest oxidation states, and it is noteworthy that the relative rates of reaction for degenerate methyl/methane exchange with Cp*2M-CH3 complexes have been observed to decrease in the order M = Y > Lu > Sc.4 In DFT studies Eisenstein and *To whom correspondence should be addressed. E-mail: m.s.hill@ bath.ac.uk. (1) (a) Schlosser, M., Organometallics in Synthesis-A Manual, 2nd ed.; Wiley: New York, 2002. (b) Clayden, J. Organolithiums: Selectivity for Synthesis; Elsevier: New York, 2002. (2) (a) Mulvey, R. E.; Mongin, F; Uchiyama, M.; Kondo, Y. Angew. Chem., Int. Ed. 2007, 46, 3802. (b) Snegaroff, K.; L’Helgoual’ch, J.-M.; Bentabed-Ababsa, C.; Nguyen, T. T.; Chevallier, F.; Yonehara, M.; Uchiyama, M.; Derdour, A.; Mongin, F. Chem.;Eur. J. 2009, 15, 10280. (c) Mulvey, R. E. Acc. Chem. Res. 2009, 42, 743. (d) Mulvey, R. E. Organometallics 2006, 25, 1060. (3) For general reviews, see: (a) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; Procopiou, P. A. Proc. R. Soc., A 2010, 466, 927. (b) Harder, S. Chem. Rev. 2010, 110, 3852. (4) (a) Watson, P. L. J. Am. Chem. Soc. 1983, 105, 6491. (b) Watson, P. L.; Parshall, G. W. Acc. Chem. Res. 1985, 18, 51. r 2010 American Chemical Society
Maron have also calculated that the larger, early lanthanides provide the lowest activation energies with a smooth progression toward decreasing activity across the 4f series.5 Although the relative facility toward related C-H reactivity of the group 2 elements may be underpinned by a similar interplay of charge density and polarization effects, consideration of the lower intrinsic charge and increasing radii (sixcoordinate radii: Ca2þ, 114; Sr2þ, 132; Ba2þ, 149 pm)6 of the electropositive alkaline earth series has led us to tentatively suggest that any discerned reactivity series is as likely to be marked by gross discontinuities as by smooth trends.7 We have recently reported a series of heavier alkaline earth dialkyl derivatives [M{CH(SiMe3)2}2(THF)n] [1: M = Ca, n = 2; 2: M = Sr, n = 3; 3: M = Ba, n = 3],8 which have the potential to operate as readily available reagents for further explorations of the reaction chemistry of both homo- and heteroleptic alkaline earth alkyl derivatives. Reactions of these species with the β-diketiminate ligand precursor [DippNC(Me)CHC(Me)NHDipp] (Dipp =2,6-di-isopropylphenyl) did not provide straightforward access to the desired heteroleptic alkyl compounds.9 Rather, the predominant reaction product in all three cases was shown to be a dimeric species in which a dianionic ligand had been formed by deprotonation of the peripheral methyl substituents of the monoanionic β-diketiminate. Although the insolubility of the strontium and barium derivatives hindered a quantitative analysis of this reactivity, the ease of formation and, by inference, the ability to effect methyl deprotonation appeared to vary in the order Ca < Sr < Ba. The methylsubstituted bis(imino)pyridine, 4 (Scheme 1), has been observed to possess a remarkable capacity either to function as a passive ancillary ligand or to undergo anionization either via hydrogen abstraction at one or both of the methyl groups attached to the imine carbon atoms or through direct alkylation.10 In the latter case C-alkylation may occur not only at the imine function but also at the C2 and, less commonly, the C3, C4, and N1 positions of a dearomatized pyridine ring. In this contribution we report that reactions of the heavier group 2 dialkyls, 1-3, and the analogous magnesium species (5) Barros, N.; Eisenstein, O.; Maron, L. Dalton Trans. 2006, 3052. (6) Shannon, R. D. Acta Crystallogr. A 1976, 32, 751. (7) Barrett, A. G. M.; Brinkmann, C.; Crimmin, M. R.; Hill, M. S.; Hunt, P.; Procopiou, P. A. J. Am. Chem. Soc. 2009, 131, 12906. (8) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; MacDougall, D. J.; Mahon, M. F.; Procopiou, P. A. Chem.-Eur. J. 2008, 14, 11292. (9) (a) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; MacDougall, D. J.; Mahon, M. F.; Procopiou, P. A., Dalton Trans. 2009, 9715. The Ca derivative had been reported previously. (b) Harder, S. Angew. Chem., Int. Ed. 2003, 42, 3430. (10) For reviews, see: (a) Knijnenburg, Q.; Gambarotta, S.; Budzelaar, P. H. M. Dalton Trans. 2006, 5442. (b) Gibson, V. C.; Redshaw, C.; Solan, G. A. Chem. Rev. 2007, 107, 1745. Published on Web 09/10/2010
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Organometallics, Vol. 29, No. 19, 2010 Scheme 1
[Mg{CH(SiMe3)2}2(THF)2], compound 5, with 4 undergo related reaction pathways involving pyridine dearomatization at the less common C3 and C4 positions as a preface to complete methyl deprotonation. The tractable nature of the reaction products allows for an initial quantitative comparison of the relative ability of alkyl group 2 species to engage in both dearomatization and directed C-H activation reactivity. Addition of the magnesium dialkyl, compound 5 (see Figure S1 for an ORTEP representation resulting from X-ray analysis of this compound), to a C6D6 solution of [2,6-{(Dipp)NC(CH3)}2C5H3N], 4, caused an instantaneous formation of an orange solution, which, from the simplicity of its 1H NMR spectrum, was inferred to contain a C2symmetric bis(imino)pyridine adduct of the dialkyl species as the only magnesium-containing compound. Monitoring of this solution heated at 60 °C by 1H NMR spectroscopy for 24 h indicated conversion of this species to a single product, compound 7, the result of deprotonation of both of the methyl groups attached to the imine substituents of the bis(imino)pyridine unit. Compound 7 was isolated as a yellow crystalline bis-THF adduct, and the structure implied from the solution-state NMR data was confirmed by an X-ray diffraction analysis (Figure S2). In contrast to the analogous reactivity observed with 1-3 (vide infra), the only identifiable intermediate species during the course of this reaction was the monodeprotonated species, compound 6, and the reaction mixture remained red-brown in color throughout the reaction. The latter observation contrasts markedly with analogous reactions performed with the heavier alkaline earth compounds 1-3 (0.17-0.20 M concentrations). Combination of the relevant metal dialkyl with 4 in C6D6 provided, in each case, the instantaneous formation of a deep blue solution. Analysis of the calcium- and strontium-based reactions by 1 H NMR spectroscopy revealed the presence of singly deprotonated species analogous to 6, compounds 8 and 9, which appeared as 20-40% of the total bis(imino)pyridinederived species in solution at the first point of analysis (Scheme 1). Further monitoring of both these reactions at 298 K indicated that 8 and 9 were consumed during the course of the continued reactions over periods of 12 and 1.5 h, respectively. The signals in the 1H NMR spectra attributed to compounds 8 and 9 appeared in both reactions alongside two further isomeric species, which were identified as the dearomatized metal alkyl compounds 10 and 11 (calcium) and 12 and 13 (strontium) formed by migration of a single alkyl residue to either the C3 or C4 positions of the pyridine ring. In contrast to these observations, the barium dialkyl 3 provided no evidence for any singly deprotonated species. Rather, the respective C3 and C4 dearomatized species, 14 and 15, were
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observed as the only intermediate products throughout the course of reaction. Although the C3 dearomatized compounds 10, 12, and 14 were present in excess (C3:C4 ratios, ca. 2:1-3:1) during the course of the respective reactions, continued NMR monitoring indicated progressive consumption of all intermediate species accompanied by a gradual fading of the blue color of the solutions into greenbrown over several hours (Ca 36 h, Sr 2 h, Ba 8 h). At this point the NMR spectra for all three reactions were reminiscent of those obtained during the synthesis of compound 7 and indicated a stoichiometric formation of calcium, strontium, and barium complexes, 16, 17, and 18, containing an identical pyridine-based ene-diamido ligand. An annotated spectrum obtained from the reaction of 2 and 4, but performed at a lower (ca. 0.04 M) concentration, is provided as Figure 1 and illustrates the clean formation of each of the intermediate species, 9, 12, and 13. Compounds 16-18 were isolated as orange, bright red, and dark red crystals, respectively, which were suitable for X-ray diffraction analyses. The calcium compound 16 was found to be mononuclear and isostructural to the Mg derivative 7 and to contain a five-coordinate Ca center comprising the tridentate ene-diamide ligand and two molecules of THF. This structure is illustrated in Figure 2a. Although compounds 17 and 18 were found to crystallize with only a single molecule of coordinated THF, the coordination number of the strontium and barium centers is maintained through an additional intermolecular (methylene) C(14)-to-group 2 element interaction such that the compounds assemble into 6-fold symmetric cyclic arrays. The hexameric unit of compound 17 is illustrated in Figure 2b, while a similar depiction of compound 18 is provided in the Supporting Information. The intermolecular M 3 3 3 CH2 contacts between the alkaline earth centers and the methylene unit of the adjacent molecule within compounds 17 and 18 [Sr-C(14)0 2.942(3); Ba-C(14)0 3.142(8) A˚] are significantly longer than either of the M 3 3 3 CH2 contacts within the recently reported products resulting from β-diketiminate methyl deprotonation [Sr-CH2 2.759(3), 2.815(3); Ba-CH2 2.966(2), 3.001(2) A˚].9 The group 2 center within each of the four complexes, 7 and 16 -18, adopts a distorted squarepyramidal coordination geometry. Unlike other compounds bearing the same ene-diamido ligand in which the pyridine ring,10 the two ene-amide functions, and the metal center are more or less coplanar, the ligand in all four alkaline earth complexes is distorted from planarity, displaying an angle ranging from 9.31° (18, Ba) to 22.52° (16, Ca) between the least-squares plane of the pyridine backbone and that formed by the ene-amide functionalities. Furthermore, the metal centers are situated at a distance of 0.645-1.220 A˚ above the pyridine plane, the distance increasing with the size of the alkaline earth metal. The deprotonation of the two former methyl groups is apparent from the values of the C-C distances [1.354(10) to 1.381(5) A˚], as expected for a conjugated double bond, while the short C-N single-bond distances [1.341(4) to 1.376(3) A˚] indicate some degree of delocalization over the ene-amide system. Kinetic data relating to the relative abilities of heavier group 2 organometallic compounds to participate in even apparently simple deprotonation chemistries are, to date, nonexistent. We undertook, therefore, to place our understanding of the course of the reactions to produce compounds 16, 17, and 18 on a more quantitative foundation. The appearance and decay of each intermediate identified in Scheme 1 as
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Figure 1. Annotated (2 h) spectrum ((a) -2 to 2.5 ppm region; (b) 3.5 to 8.5 region) obtained from the reaction of 2 and 4 (0.04 M) illustrating the formation of 17 and each of the intermediate species. The numbers in the colored boxes refer to the assignments indicated for 4 (yellow), 12 (green), 13 (blue), 9 (orange), and 17 (red).
well as the consumption of the ligand precursor 4 and the production of the final doubly deprotonated products were readily monitored and evidenced some rather complex metaldependent behavior. From experiments undertaken at 298 K and with 0.10 M concentrations of the reagents, it was apparent that although the barium dialkyl provided the most rapid, effectively instantaneous, consumption of 4 (Figure 3), this did not translate to the most facile formation of the final doubly deprotonated product. In addition, the failure to observe a barium-centered analogue of the singly deprotonated complexes, 6, 8, and 9, indicated that the dearomatized intermediate species 14 and 15 possess enhanced stability for this heaviest and most electropositive member of the group 2
series. This observation was further borne out by direct monitoring of the total concentration of the two dearomatized species for each metal (Figure 4). Although the appearance and decline of each of these species could not be fitted to any simple rate dependence, it may be inferred that the subsequent proposed intermediate, a singly deprotonated barium complex analogous to 8 and 9, is consumed immediately to form the ultimate reaction product, compound 18. Monitoring of the consumption of compound 4 in reactions with compound 1 or 2 provided an apparent first-order dependence upon both [4] and [1 or 2] such that -d[4]/dt = k[4][1 or 2] and provided k = 0.0713 mol-1 min-1 for 1 and k = 0.468 mol-1 min-1 for 2. From these data it is further
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Figure 4. Total concentration of dearomatized intermediates (i.e., 10 þ 11, 12 þ 13, 14 þ 15) observed during reactions of ligand precursor 4 with 1 (green), 2 (red), and 3 (blue).
Figure 2. (a) ORTEP representation of compound 16. (b) Hexameric unit of compound 17. Thermal ellipsoids are set at 25% probability, and H atoms, except for the methylene protons within 16, and isopropyl methyl groups are removed for clarity.
Figure 3. Disappearance of ligand precursor 4 in reaction with 1 (green), 2 (red), and 3 (blue) (Ba . Sr > Ca).
apparent that the reactivity series of the metal dialkyl toward an initial reaction with 4 vary in the order Ba > Sr > Ca, which may be a simple reflection of the increasing M2þ radii and access to the metal center on descending the group. Conversely, the rate of formation of the final
Figure 5. Formation of products 16 (9), 17 (2), and 18 (().
reaction products, 16 to 18 (Figure 5), is then a more complex interplay of the stability of the various dearomatized and deprotonated intermediate species that varies in the order Sr > Ba > Ca. Although complex, and sharing common features, these data illustrate that it is a likely fallacy to consider the reactivity of the heavier members of group 2 as identical. It is apparent that the activation barriers toward the individual molecular steps encountered in the construction of a typical catalytic cycle will also show a more nuanced dependence upon the identity of the alkaline earth cation. In summary, gross variation of M2þ cation size may be the most conspicuous consequence of increasing atomic weight, but not the sole consideration.
Acknowledgment. We thank the Engineering and Physical Sciences Research Council for a project studentship (M.A., EP/E03117X/1). Supporting Information Available: Experimental procedures, compound characterization data, X-ray analyses, and kinetic data. This material is available free of charge via the Internet at http://pubs.acs.org.
