DOI: 10.1002/chem.201500986
Communication
& Asymmetric Synthesis
Absolute Asymmetric Synthesis of a Tetrahedral Silver Complex Per Martin Bjçremark, Susanne Olsson, Theonitsa Kokoli, and Mikael Hkansson*[a] Abstract: Even though the isolation of tetrahedral stereoisomers usually presents a synthetic challenge, a highly enantioenriched tetrahedral silver complex could be easily accessed by either crystallization or Viedma ripening. The overall preparation may be regarded as an example of absolute asymmetric synthesis. Experimental results indicate that both crystallization and Viedma ripening follow a similar cluster-controlled mechanism.
Organic stereochemistry is based on tetrahedral geometry. In sharp contrast, inorganic stereochemistry based on tetrahedral (T-4) metal complexes is virtually unexplored,[1–2] especially if complexes with chiral ligands or quasi-tetrahedral geometry are excluded.[3] One reason for this is the inherent lability of most tetrahedral metal complexes, causing rapid interconversion in solution at ambient conditions. Thus, the isolation of T4 stereoisomers is a synthetic challenge. We set out to try with [M(ab)2] complexes because they are chiral and homoleptic (Figure 1). When trying to isolate T-4 enantiomers, it is gratifying that the lability, which makes traditional resolution so difficult, can be turned into a useful property. If enantiomerization in solution is possible (Scheme 1), then either enantiomer can be exclusively crystallized in up to 100 % yield and enantiomeric excess (ee).[4] If the crystallization starts without seeding, the overall preparation may also be regarded as absolute asymmetric synthesis (AAS),[5] that is the creation of optical activity
Figure 1. Tetrahedral chiral complexes with achiral mono- or bidentate ligands.
[a] P. M. Bjçremark, Dr. S. Olsson, Dr. T. Kokoli, Prof. M. Hkansson Department of Chemistry and Molecular Biology University of Gothenburg, 412 96 Gothenburg (Sweden) E-mail: [email protected] Chem. Eur. J. 2015, 21, 8750 – 8753
Scheme 1. Enantiopure crystal batches of either handedness can be obtained by crystallization.
from achiral (or racemic) precursors. AAS and asymmetric autocatalysis[6] are relevant in connection to the origin of biomolecular homochirality.[7] We have previously reported AAS of five-, seven-, and eight-coordinate metal complexes.[8] We primarily searched for labile conglomerates among coinage metal complexes; they frequently exhibit tetrahedral coordination geometry and soft ligands, such as sulfides[9] or phosphines, so we concentrated on bidentate S/P ligands. We found that [Ag(PS)2]BF4 (1; PS = (2-(methylthio)ethyl)diphenylphosphine) forms a conglomerate, and we were able to determine the crystal structure for both enantiomers (Figure 2). The coordination geometry around Ag1 is distorted tetrahedral, and the sulfur atoms adopt an R configuration in D-1 and an S configuration in L-1. Determining the ee in a crystal batch of 1 is nontrivial because the complex racemizes as soon as it is dissolved, as demonstrated by the lack of a CD (circular dichroism) signal. Only solid-state methods are, thus, viable and for microcrystalline samples single-crystal analysis, which otherwise is the most powerful method, is not very helpful. We have, however, recently demonstrated how solid-state CD spectroscopy[10] can be used for quantitative determination of ee in bulk samples.[8b, 11] By using this solid-state CD method, we could demonstrate AAS of 1. Single crystals were used to record reference solid state CD spectra of the two enantiomers of 1 (Figure 3). Subsequently, a correlation between the magnitude of the CD signal and the mass of enantiopure 1 could be established.[8b, 11] Nine crystallizations of 1 from neat CH2Cl2 gave crystal batches with an average of 89 % ee and quantitative yield. The
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Figure 2. ORTEP drawing of the cation in (L,S,S)-1. Selected bond lengths [æ] and angles [8]: Ag1¢S1 2.479(2), Ag1¢P1 2.408(1), P1-Ag1-P1* 154.1(1), S1-Ag1-P1 116.0(1), S1-Ag1-P1* 82.9(1), S1-Ag1-S1* 91.2(1).
Figure 3. Superimposed solid-state CD spectra of (a) (L,S,S)-1 and (b) (D,R,R)-1.
mechanism that is usually inferred in symmetry-breaking crystallizations involves primary nucleation (or seeding) of an Adam crystal, which then can spawn secondary nuclei, for example, by stirring.[12] Circumstantial evidence renders an Adam Chem. Eur. J. 2015, 21, 8750 – 8753
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mechanism questionable here: neither seeding nor stirring was required and the solution was highly concentrated and supersaturated (the solubility of 1 in CH2Cl2 is about 1.0 g mL¢1), which should result in primary nucleation of competing nuclei and subsequent reduction of ee. An alternative mechanism based on symmetry-breaking cluster formation in a supersaturated solution, driven by, for example, temperature gradients,[13] has been described by Ribû and co-workers.[14] Indeed, an evaporating CH2Cl2 solution will maintain a temperature gradient; this gradient disappears when a layer of a less volatile solvent is added on top of the CH2Cl2 solution. To probe for a temperature gradient influence, we performed ten crystallizations of 1 from CH2Cl2 solutions layered with toluene, which lowered the average ee to 58 %. The significantly higher ee (89 %) obtained from neat CH2Cl2 solutions (exhibiting a temperature gradient) could be due to cluster-based symmetry-breaking, occurring before crystals of 1 actually form.[14] In his seminal 2005 discovery, Cristobal Viedma showed that simple grinding of a racemic conglomerate can cause complete deracemization within a few hours.[15a] Although the mechanism is still under debate,[13–15] such Viedma ripening has considerable potential for the large-scale production of, for example, pharmaceuticals, but remains to be explored for metal complexes following Rybak’s pioneering study.[16] We were intrigued to find that prolonged grinding with a mortar and pestle of a powder of 1 for KBr discs indeed increased the magnitude of the CD signal, which could either be due to Viedma ripening or, less interestingly, simply due to a reduction in size of the particles. The magnitude of the CD signal increases for smaller particles. To differentiate between these cases, we placed a large single crystal (known to be enantiopure) in a round-bottomed flask with exclusion of light, suspended the crystal in toluene and used glass beads and a magnetic stirrer to grind the crystal into a powder. Small aliquots of the suspensions were collected every twelve hours, from which the solvent was removed and the powder dried under a stream of nitrogen gas and quickly mixed with KBr and pressed into a disc. The average CD amplitude rose to a maximum value of 33 mdeg mg¢1 over a few days and remained at the maximum value until the grinding was interrupted after two weeks. The experiment was repeated five times with the same result. Samples ground by glass beads in this way were examined with a microscope; the particles were of a uniform size (0.5–1.5 mm). Having thus established the CD amplitude for enantiopure particles of this size, we ground entire crystal batches obtained by slow crystallization. Although the starting CD amplitude differed between the batches, all examined batches rose to a maximum value of about 33 mdeg mg¢1 after 12–120 h, indicating enantiopurity. Two such batches of preground single crystals of opposite chirality were mixed and ground further. Starting from a low value, the CD amplitude rose to the maximum value of 33 mdeg mg¢1 over a few days (Figure 4). The process could be repeated several times by adding more of the opposite enantiomer. The conclusion must be that this is a rare example of a chiral metal complex undergoing attritionenhanced deracemization to enantiopurity.
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Figure 4. Three separate grinding experiments starting from near-racemic mixtures of previously ground crystals of (L,S,S)-1 and (D,R,R)-1. A specific CD amplitude of 33 mdeg mg¢1 corresponds to 100 % ee.
In conclusion, we have shown that a highly enantioenriched tetrahedral silver complex can be easily accessed by either crystallization or Viedma ripening. Moreover, it is possible that both processes follow a similar cluster-controlled mechanism.[14]
tube. The solution was allowed to evaporate to dryness (over approx. 15 h) at ambient temperature with exclusion of light. The crystal batch was carefully ground to a fine powder. To the sample (1.00 mg), FT-IR grade KBr (999.0 mg) was added in small portions while mixing and grinding. From this mixture, 100.0 mg was pressed into a disc. The CD signals at 247 and 286 nm were averaged over several different disc orientations. A corresponding measurement was made on a carefully selected single crystal (0.042 mg in 100 mg KBr). The averaged CD signal was 7.32 mdeg for the single crystal and 15.8 mdeg for the bulk sample, showing an enantiomeric excess of approximately 90 %. (b) Ten crystallizations, in which a CH2Cl2 solution was layered with toluene were made, yielding crystal batches with an average ee of 58 %; six (D,R,R)-batches and four (L,S,S)-batches were obtained. In a typical crystallization, racemic 1 (30 mg) was dissolved in CH2Cl2 (1.0 mL) and layered with toluene (3.0 mL) in a test-tube. A crystal batch (16 mg) of 1 was collected after 48 h (crystallization started after 10 h) and the ee was measured as previously described.
Correlation between CD spectra and absolute configuration was obtained by single-crystal X-ray diffraction analysis followed by a solid-state CD analysis on the very same crystal. The lack of CD signal in CH2Cl2 solution shows that a dissolved crystal of 1 racemizes in less than 10 s at ambient temperature.
Grinding
Experimental Section Operations were performed with exclusion of light by using standard Schlenk techniques. The PS ligand (2-(methylthio)ethyl)diphenylphosphine) was synthesized according to literature.[17] Reflections obtained from a Rigaku RU/H3R rotating anode X-ray generator were recorded by a Rigaku R-Axis IIc image plate system. Solution and solid-state CD spectra were recorded on a Jasco J-715 spectropolarimeter. NMR and IR spectra were recorded on a Jeol JNM-ECP400 FT-NMR and a PerkinElmer Spectrum One FT-IR, respectively. MS spectra were collected with a Q-Star Pulsar quadrupole time-of-flight instrument, equipped with a nanospray ion source. Particle sizes in ground samples were determined using a Zeiss Axiotech microscope.
Synthesis of [Ag(PS)2]BF4 (1) AgBF4 (0.13 g; 0.67 mmol) and (2-(methylthio)ethyl)diphenylphosphine (0.35 g; 1.34 mmol) were dissolved in dry CH2Cl2 (3 mL) by stirring for 30 min. The resulting pale yellow solution was filtered and evaporated to dryness; the product was washed with hexane (2 mL). Yield: 0.47 g (98 %); 1H NMR (CDCl3, 400 MHz): d = 7.60–7.52 (m, 4 H, Ar), 7.52–7.41 (m, 6 H, Ar), 2.86 (m, 2 H, CH2), 2.78 (m, 2 H, CH2), 2.24 (s, 3 H, SCH3); IR (KBr): v˜ = 3052 (w), 2916 (w), 1482 (m), 1436 (s), 1404 (m), 1385 (s), 1332 (w), 1307 (w), 1278 (w), 1258 (m), 1188 (w), 1160 (m), 1108 (s), 1055 (vs), 998 (m), 899 (m), 877 (w), 832 (m), 751 (m), 742 (m), 695 cm¢1 (m); ESI-MS(CH3CN): m/z (%): 627.0 [Ag(PS)2] + (100).
Crystallizations (a) Nine crystallizations from neat CH2Cl2 were made, yielding crystal batches with an average ee of 89 % (quantitative yield); five (D,R,R)-batches and four (L,S,S)-batches were obtained. In a typical crystallization, 1 (10 mg) was dissolved in CH2Cl2 (0.5 mL) in a testChem. Eur. J. 2015, 21, 8750 – 8753
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[Ag(PS)2]BF4 (0.40 g, 0.56 mmol) was ground to a coarse powder with a mortar and pestle. The powder was added to a 25 mL round-bottomed flask along with toluene (15 mL) and glass beads (4 g, ø 1 mm) and ground for 3 d until a sample of 0.1 mg/100 mg KBr gave an average CD amplitude for the signals at 286 nm and 247 nm reached a consistent value of 33 mdeg. The mixture was centrifuged and the powder dried in a stream of nitrogen. The resulting powder was homogenous, containing particles of 0.5– 1.5 mm size.
Viedma deracemization Two batches prepared as above of the opposite enantiomers (35 mg of each) was placed in a 25 mL round-bottomed flask along with glass beads (5 g, ø 1 mm) and toluene (20 mL) and ground for 142 h during which samples of the slurry containing 1– 3 mg powder were removed and analyzed by CD spectroscopy. The increase of the average CD amplitude for the signals at 247 and 286 nm of a sample (0.1 mg/100 mg KBr) was followed by CD spectroscopy. Each KBr disc was rotated in the beam and the CD spectra from 10 different positions were averaged.
Crystal structure Crystal structure data for AgP2S2BF4C30H34 (D-1, similar for L-1): crystal size: 0.20 Õ 0.20 Õ 0.20 mm, trigonal, P3121, a = 9.8236(11), c = 29.107(6) æ, V = 2432.6(5) æ3, Z = 3, 1calcd = 1.465 g cm¢3, 2qmax = 52.08, MoKa radiation, T = 20 8C, m = 0.891 mm¢1. Refinement on F2 for 3126 reflections and 199 parameters gave R1 = 0.0555 and wR2 = 0.1470 for all data with ¢0.63 < D1 < 0.62 e æ¢3. The absolute structure (Flack) parameter[18] was 0.04(5). All non-hydrogen atoms were refined with anisotropic thermal displacement parameters. The structures were solved and refined with SHELX-97[19] under the WinGX program package.[20a] Figure 3 and 4 were drawn with ORTEP3 for Windows.[20b] CCDC-818727 (L-1) and CCDC-
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Communication 818728 (D-1) contain the supplementary crystallographic data (excluding structure factors) for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements This work was supported by the Swedish Research Council (VR). Keywords: asymmetric synthesis · chirality · inorganic stereochemistry · metal complexes · Viedma ripening [1] A. von Zelewsky, Stereochemistry of Coordination Compounds, Wiley, New York, 1996, pp. 75 – 100. [2] a) W. H. Mills, R. A. Gotts, J. Chem. Soc. 1926, 129, 3121; b) J. C. I. Liu, J. C. Bailar, J. Am. Chem. Soc. 1951, 73, 5432. [3] H. Brunner, Angew. Chem. Int. Ed. 1999, 38, 1194; Angew. Chem. 1999, 111, 1248. [4] E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of Organic Compounds, Wiley, New York, 1994, pp. 315 – 316 and 1207. [5] a) B. L. Feringa, R. A. Van Delden, Angew. Chem. Int. Ed. 1999, 38, 3418; Angew. Chem. 1999, 111, 3624 – 3645; b) K. Mislow, Collect. Czech. Chem. Commun. 2003, 68, 849; c) M. Vestergren, B. Gustafsson, O. Davidsson, M. Hakansson, Angew. Chem. Int. Ed. 2000, 39, 3435; Angew. Chem. 2000, 112, 3577; d) M. Vestergren, J. Eriksson, M. Hakansson, Chem. Eur. J. 2003, 9, 4678; e) A. Lennartson, S. Olsson, J. Sundberg, M. Hakansson, Angew. Chem. Int. Ed. 2009, 48, 3137; Angew. Chem. 2009, 121, 3183; f) S. Olsson, A. Lennartson, M. Hakansson, Chem. Eur. J. 2013, 19, 12415; g) S. Olsson, P. M. Bjçremark, T. Kokoli, J. Sundberg, A. Lennartson, C. J. McKenzie, M. Hakansson, Chem. Eur. J. 2015, 21, 5211 – 5219. [6] a) K. Soai, I. Sato, T. Shibata, S. Komiya, M. Hayashi, Y. Matsueda, H. Imamura, T. Hayase, H. Morioka, H. Tabira, J. Yamamoto, Y. Kowata, Tetrahedron: Asymmetry 2003, 14, 185; b) K. Soai, T. Shibata, H. Morioka, K. Choji, Nature 1995, 378, 767; c) K. Soai, T. Shibata, I. Sato, Acc. Chem. Res. 2000, 33, 382. [7] a) A. Saghatelian, Y. Yokobayashi, K. Soltani, M. R. Ghadiri, Nature 2001, 409, 797; b) G. L. J. A. Rikken, E. Raupach, Nature 2000, 405, 932; c) M. Avalos, R. Babiano, P. Cintas, J. L. Jimenez, J. C. Palacios, L. D. Barron, Chem. Rev. 1998, 98, 2391; d) J. S. Siegel, Nature 2002, 419, 346. [8] a) M. Hkansson, M. Vestergren, B. Gustafsson, G. Hilmersson, Angew. Chem. Int. Ed. 1999, 38, 2199; Angew. Chem. 1999, 111, 2336; b) A. Lennartson, M. Vestergren, M. Hakansson, Chem. Eur. J. 2005, 11, 1757; c) A. Lennartson, M. Hakansson, Angew. Chem. Int. Ed. 2009, 48, 5869; Angew. Chem. 2009, 121, 5983.
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[9] Sulfide ligands are especially interesting in this context because the sulfur atom can become chirogenic upon coordination to a metal center; enantioselective ligand oxidation to sulfoxide will thus be a possible application of such enantiopure T-4 complexes. [10] R. Kuroda, T. Honma, Chirality 2000, 12, 269. [11] A. Johansson, M. Hakansson, Chem. Eur. J. 2005, 11, 5238. [12] a) D. K. Kondepudi, R. J. Kaufman, N. Singh, Science 1990, 250, 975; b) D. K. Kondepudi, J. Laudadio, K. Asakura, J. Am. Chem. Soc. 1999, 121, 1448. [13] a) Z. El-Hachemi, J. Crusats, J. M. Ribû, Cryst. Growth Des. 2009, 9, 4802; b) P. Cintas, C. Viedma, Chem. Commun. 2011, 47, 12786. [14] a) C. Blanco, J. Crusats, Z. El-Hachemi, A. Moyano, S. Veintemillas-Verdaguer, D. Hochberg, J. M. Ribû, ChemPhysChem 2013, 14, 3982; b) J. M. Ribû, C. Blanco, J. Crusats, Z. El-Hachemi, D. Hochberg, A. Moyano, Chem. Eur. J. 2014, 20, 17250. [15] a) C. Viedma, Phys. Rev. Lett. 2005, 94, 065504; b) J. Crusats, S. Veintemillas-Verdaguer, J. M. Ribû, Chem. Eur. J. 2006, 12, 7776; c) C. Viedma, Cryst. Growth Des. 2007, 7, 553; d) C. Viedma, J. E. Ortiz, T. Izumi, D. G. Blackmond, J. Am. Chem. Soc. 2008, 130, 15274; e) W. L. Noorduin, B. Kaptein, H. Meekes, W. J. P. van Enckevort, R. M. Kellogg, E. Vlieg, Angew. Chem. Int. Ed. 2009, 48, 4581; Angew. Chem. 2009, 121, 4651; f) S. B. Tsogoeva, S. Wei, M. Freund, M. Mauksch, Angew. Chem. Int. Ed. 2009, 48, 590; Angew. Chem. 2009, 121, 598; g) W. L. Noorduin, W. J. P. van Enckevort, H. Meekes, B. Kaptein, M. Leeman, R. M. Kellogg, E. Vlieg, Angew. Chem. Int. Ed. 2009, 48, 3278; Angew. Chem. 2009, 121, 3328; h) W. L. Noorduin, E. Vlieg, R. M. Kellogg, B. Kaptein, Angew. Chem. Int. Ed. 2009, 48, 9600; Angew. Chem. 2009, 121, 9778; i) W. L. Noorduin, W. J. P. van Enckevort, H. Meekes, B. Kaptein, R. M. Kellogg, J. C. Tully, J. M. McBride, E. Vlieg, Angew. Chem. Int. Ed. 2010, 49, 8435; Angew. Chem. 2010, 122, 8613; j) Z. El-Hachemi, J. Crusats, J. M. Ribû, J. M. McBride, S. Veintemillas-Verdaguer, Angew. Chem. Int. Ed. 2011, 50, 2359; Angew. Chem. 2011, 123, 2407; k) J. E. Hein, B. H. Cao, C. Viedma, R. M. Kellogg, D. G. Blackmond, J. Am. Chem. Soc. 2012, 134, 12629; l) D. T. McLaughlin, T. P. T. Nguyen, L. Mengnjo, C. Bian, Y. H. Leung, E. Goodfellow, P. Ramrup, S. Woo, L. A. Cuccia, Cryst. Growth Des. 2014, 14, 1067. [16] W. K. Rybak, Tetrahedron: Asymmetry 2008, 19, 2234. [17] P. A. Ulmann, A. M. Brown, M. V. Ovchinnikov, C. A. Mirkin, A. G. DiPasquale, A. L. Rheingold, Chem. Eur. J. 2007, 13, 4529. [18] a) H. D. Flack, G. Bernardinelli, J. Appl. Crystallogr. 2000, 33, 1143; b) H. D. Flack, G. Bernardinelli, Acta Crystallogr. Sect. A 1999, 55, 908. [19] G. M. Sheldrick, Acta Crystallogr. Sect. A 2008, 64, 112. [20] a) L. J. Farrugia, J. Appl. Crystallogr. 1999, 32, 837; b) L. J. Farrugia, J. Appl. Crystallogr. 1997, 30, 565.
Received: March 12, 2015 Published online on May 4, 2015
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Communication
& Asymmetric Synthesis
Absolute Asymmetric Synthesis of a Tetrahedral Silver Complex Per Martin Bjçremark, Susanne Olsson, Theonitsa Kokoli, and Mikael Hkansson*[a] Abstract: Even though the isolation of tetrahedral stereoisomers usually presents a synthetic challenge, a highly enantioenriched tetrahedral silver complex could be easily accessed by either crystallization or Viedma ripening. The overall preparation may be regarded as an example of absolute asymmetric synthesis. Experimental results indicate that both crystallization and Viedma ripening follow a similar cluster-controlled mechanism.
Organic stereochemistry is based on tetrahedral geometry. In sharp contrast, inorganic stereochemistry based on tetrahedral (T-4) metal complexes is virtually unexplored,[1–2] especially if complexes with chiral ligands or quasi-tetrahedral geometry are excluded.[3] One reason for this is the inherent lability of most tetrahedral metal complexes, causing rapid interconversion in solution at ambient conditions. Thus, the isolation of T4 stereoisomers is a synthetic challenge. We set out to try with [M(ab)2] complexes because they are chiral and homoleptic (Figure 1). When trying to isolate T-4 enantiomers, it is gratifying that the lability, which makes traditional resolution so difficult, can be turned into a useful property. If enantiomerization in solution is possible (Scheme 1), then either enantiomer can be exclusively crystallized in up to 100 % yield and enantiomeric excess (ee).[4] If the crystallization starts without seeding, the overall preparation may also be regarded as absolute asymmetric synthesis (AAS),[5] that is the creation of optical activity
Figure 1. Tetrahedral chiral complexes with achiral mono- or bidentate ligands.
[a] P. M. Bjçremark, Dr. S. Olsson, Dr. T. Kokoli, Prof. M. Hkansson Department of Chemistry and Molecular Biology University of Gothenburg, 412 96 Gothenburg (Sweden) E-mail: [email protected] Chem. Eur. J. 2015, 21, 8750 – 8753
Scheme 1. Enantiopure crystal batches of either handedness can be obtained by crystallization.
from achiral (or racemic) precursors. AAS and asymmetric autocatalysis[6] are relevant in connection to the origin of biomolecular homochirality.[7] We have previously reported AAS of five-, seven-, and eight-coordinate metal complexes.[8] We primarily searched for labile conglomerates among coinage metal complexes; they frequently exhibit tetrahedral coordination geometry and soft ligands, such as sulfides[9] or phosphines, so we concentrated on bidentate S/P ligands. We found that [Ag(PS)2]BF4 (1; PS = (2-(methylthio)ethyl)diphenylphosphine) forms a conglomerate, and we were able to determine the crystal structure for both enantiomers (Figure 2). The coordination geometry around Ag1 is distorted tetrahedral, and the sulfur atoms adopt an R configuration in D-1 and an S configuration in L-1. Determining the ee in a crystal batch of 1 is nontrivial because the complex racemizes as soon as it is dissolved, as demonstrated by the lack of a CD (circular dichroism) signal. Only solid-state methods are, thus, viable and for microcrystalline samples single-crystal analysis, which otherwise is the most powerful method, is not very helpful. We have, however, recently demonstrated how solid-state CD spectroscopy[10] can be used for quantitative determination of ee in bulk samples.[8b, 11] By using this solid-state CD method, we could demonstrate AAS of 1. Single crystals were used to record reference solid state CD spectra of the two enantiomers of 1 (Figure 3). Subsequently, a correlation between the magnitude of the CD signal and the mass of enantiopure 1 could be established.[8b, 11] Nine crystallizations of 1 from neat CH2Cl2 gave crystal batches with an average of 89 % ee and quantitative yield. The
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Figure 2. ORTEP drawing of the cation in (L,S,S)-1. Selected bond lengths [æ] and angles [8]: Ag1¢S1 2.479(2), Ag1¢P1 2.408(1), P1-Ag1-P1* 154.1(1), S1-Ag1-P1 116.0(1), S1-Ag1-P1* 82.9(1), S1-Ag1-S1* 91.2(1).
Figure 3. Superimposed solid-state CD spectra of (a) (L,S,S)-1 and (b) (D,R,R)-1.
mechanism that is usually inferred in symmetry-breaking crystallizations involves primary nucleation (or seeding) of an Adam crystal, which then can spawn secondary nuclei, for example, by stirring.[12] Circumstantial evidence renders an Adam Chem. Eur. J. 2015, 21, 8750 – 8753
www.chemeurj.org
mechanism questionable here: neither seeding nor stirring was required and the solution was highly concentrated and supersaturated (the solubility of 1 in CH2Cl2 is about 1.0 g mL¢1), which should result in primary nucleation of competing nuclei and subsequent reduction of ee. An alternative mechanism based on symmetry-breaking cluster formation in a supersaturated solution, driven by, for example, temperature gradients,[13] has been described by Ribû and co-workers.[14] Indeed, an evaporating CH2Cl2 solution will maintain a temperature gradient; this gradient disappears when a layer of a less volatile solvent is added on top of the CH2Cl2 solution. To probe for a temperature gradient influence, we performed ten crystallizations of 1 from CH2Cl2 solutions layered with toluene, which lowered the average ee to 58 %. The significantly higher ee (89 %) obtained from neat CH2Cl2 solutions (exhibiting a temperature gradient) could be due to cluster-based symmetry-breaking, occurring before crystals of 1 actually form.[14] In his seminal 2005 discovery, Cristobal Viedma showed that simple grinding of a racemic conglomerate can cause complete deracemization within a few hours.[15a] Although the mechanism is still under debate,[13–15] such Viedma ripening has considerable potential for the large-scale production of, for example, pharmaceuticals, but remains to be explored for metal complexes following Rybak’s pioneering study.[16] We were intrigued to find that prolonged grinding with a mortar and pestle of a powder of 1 for KBr discs indeed increased the magnitude of the CD signal, which could either be due to Viedma ripening or, less interestingly, simply due to a reduction in size of the particles. The magnitude of the CD signal increases for smaller particles. To differentiate between these cases, we placed a large single crystal (known to be enantiopure) in a round-bottomed flask with exclusion of light, suspended the crystal in toluene and used glass beads and a magnetic stirrer to grind the crystal into a powder. Small aliquots of the suspensions were collected every twelve hours, from which the solvent was removed and the powder dried under a stream of nitrogen gas and quickly mixed with KBr and pressed into a disc. The average CD amplitude rose to a maximum value of 33 mdeg mg¢1 over a few days and remained at the maximum value until the grinding was interrupted after two weeks. The experiment was repeated five times with the same result. Samples ground by glass beads in this way were examined with a microscope; the particles were of a uniform size (0.5–1.5 mm). Having thus established the CD amplitude for enantiopure particles of this size, we ground entire crystal batches obtained by slow crystallization. Although the starting CD amplitude differed between the batches, all examined batches rose to a maximum value of about 33 mdeg mg¢1 after 12–120 h, indicating enantiopurity. Two such batches of preground single crystals of opposite chirality were mixed and ground further. Starting from a low value, the CD amplitude rose to the maximum value of 33 mdeg mg¢1 over a few days (Figure 4). The process could be repeated several times by adding more of the opposite enantiomer. The conclusion must be that this is a rare example of a chiral metal complex undergoing attritionenhanced deracemization to enantiopurity.
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Communication
Figure 4. Three separate grinding experiments starting from near-racemic mixtures of previously ground crystals of (L,S,S)-1 and (D,R,R)-1. A specific CD amplitude of 33 mdeg mg¢1 corresponds to 100 % ee.
In conclusion, we have shown that a highly enantioenriched tetrahedral silver complex can be easily accessed by either crystallization or Viedma ripening. Moreover, it is possible that both processes follow a similar cluster-controlled mechanism.[14]
tube. The solution was allowed to evaporate to dryness (over approx. 15 h) at ambient temperature with exclusion of light. The crystal batch was carefully ground to a fine powder. To the sample (1.00 mg), FT-IR grade KBr (999.0 mg) was added in small portions while mixing and grinding. From this mixture, 100.0 mg was pressed into a disc. The CD signals at 247 and 286 nm were averaged over several different disc orientations. A corresponding measurement was made on a carefully selected single crystal (0.042 mg in 100 mg KBr). The averaged CD signal was 7.32 mdeg for the single crystal and 15.8 mdeg for the bulk sample, showing an enantiomeric excess of approximately 90 %. (b) Ten crystallizations, in which a CH2Cl2 solution was layered with toluene were made, yielding crystal batches with an average ee of 58 %; six (D,R,R)-batches and four (L,S,S)-batches were obtained. In a typical crystallization, racemic 1 (30 mg) was dissolved in CH2Cl2 (1.0 mL) and layered with toluene (3.0 mL) in a test-tube. A crystal batch (16 mg) of 1 was collected after 48 h (crystallization started after 10 h) and the ee was measured as previously described.
Correlation between CD spectra and absolute configuration was obtained by single-crystal X-ray diffraction analysis followed by a solid-state CD analysis on the very same crystal. The lack of CD signal in CH2Cl2 solution shows that a dissolved crystal of 1 racemizes in less than 10 s at ambient temperature.
Grinding
Experimental Section Operations were performed with exclusion of light by using standard Schlenk techniques. The PS ligand (2-(methylthio)ethyl)diphenylphosphine) was synthesized according to literature.[17] Reflections obtained from a Rigaku RU/H3R rotating anode X-ray generator were recorded by a Rigaku R-Axis IIc image plate system. Solution and solid-state CD spectra were recorded on a Jasco J-715 spectropolarimeter. NMR and IR spectra were recorded on a Jeol JNM-ECP400 FT-NMR and a PerkinElmer Spectrum One FT-IR, respectively. MS spectra were collected with a Q-Star Pulsar quadrupole time-of-flight instrument, equipped with a nanospray ion source. Particle sizes in ground samples were determined using a Zeiss Axiotech microscope.
Synthesis of [Ag(PS)2]BF4 (1) AgBF4 (0.13 g; 0.67 mmol) and (2-(methylthio)ethyl)diphenylphosphine (0.35 g; 1.34 mmol) were dissolved in dry CH2Cl2 (3 mL) by stirring for 30 min. The resulting pale yellow solution was filtered and evaporated to dryness; the product was washed with hexane (2 mL). Yield: 0.47 g (98 %); 1H NMR (CDCl3, 400 MHz): d = 7.60–7.52 (m, 4 H, Ar), 7.52–7.41 (m, 6 H, Ar), 2.86 (m, 2 H, CH2), 2.78 (m, 2 H, CH2), 2.24 (s, 3 H, SCH3); IR (KBr): v˜ = 3052 (w), 2916 (w), 1482 (m), 1436 (s), 1404 (m), 1385 (s), 1332 (w), 1307 (w), 1278 (w), 1258 (m), 1188 (w), 1160 (m), 1108 (s), 1055 (vs), 998 (m), 899 (m), 877 (w), 832 (m), 751 (m), 742 (m), 695 cm¢1 (m); ESI-MS(CH3CN): m/z (%): 627.0 [Ag(PS)2] + (100).
Crystallizations (a) Nine crystallizations from neat CH2Cl2 were made, yielding crystal batches with an average ee of 89 % (quantitative yield); five (D,R,R)-batches and four (L,S,S)-batches were obtained. In a typical crystallization, 1 (10 mg) was dissolved in CH2Cl2 (0.5 mL) in a testChem. Eur. J. 2015, 21, 8750 – 8753
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[Ag(PS)2]BF4 (0.40 g, 0.56 mmol) was ground to a coarse powder with a mortar and pestle. The powder was added to a 25 mL round-bottomed flask along with toluene (15 mL) and glass beads (4 g, ø 1 mm) and ground for 3 d until a sample of 0.1 mg/100 mg KBr gave an average CD amplitude for the signals at 286 nm and 247 nm reached a consistent value of 33 mdeg. The mixture was centrifuged and the powder dried in a stream of nitrogen. The resulting powder was homogenous, containing particles of 0.5– 1.5 mm size.
Viedma deracemization Two batches prepared as above of the opposite enantiomers (35 mg of each) was placed in a 25 mL round-bottomed flask along with glass beads (5 g, ø 1 mm) and toluene (20 mL) and ground for 142 h during which samples of the slurry containing 1– 3 mg powder were removed and analyzed by CD spectroscopy. The increase of the average CD amplitude for the signals at 247 and 286 nm of a sample (0.1 mg/100 mg KBr) was followed by CD spectroscopy. Each KBr disc was rotated in the beam and the CD spectra from 10 different positions were averaged.
Crystal structure Crystal structure data for AgP2S2BF4C30H34 (D-1, similar for L-1): crystal size: 0.20 Õ 0.20 Õ 0.20 mm, trigonal, P3121, a = 9.8236(11), c = 29.107(6) æ, V = 2432.6(5) æ3, Z = 3, 1calcd = 1.465 g cm¢3, 2qmax = 52.08, MoKa radiation, T = 20 8C, m = 0.891 mm¢1. Refinement on F2 for 3126 reflections and 199 parameters gave R1 = 0.0555 and wR2 = 0.1470 for all data with ¢0.63 < D1 < 0.62 e æ¢3. The absolute structure (Flack) parameter[18] was 0.04(5). All non-hydrogen atoms were refined with anisotropic thermal displacement parameters. The structures were solved and refined with SHELX-97[19] under the WinGX program package.[20a] Figure 3 and 4 were drawn with ORTEP3 for Windows.[20b] CCDC-818727 (L-1) and CCDC-
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Communication 818728 (D-1) contain the supplementary crystallographic data (excluding structure factors) for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Received: March 12, 2015 Published online on May 4, 2015
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