Crystallization-Induced Dynamic Resolution of Stereolabile Biaryl

Communication pubs.acs.org/crystal

Crystallization-Induced Dynamic Resolution of Stereolabile Biaryl Derivatives Involving Supramolecular Interactions H. Degenbeck,† A.-S. Felten,† J. Etxebarria,† E. C. Escudero-Adán,† J. Benet-Buchholz,† and A. Vidal-Ferran*,†,‡ †

Institute of Chemical Research of Catalonia (ICIQ), Avgda. Països Catalans 16, 43007 Tarragona, Spain Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain

‡

S Supporting Information *

ABSTRACT: Dynamic atroposelective resolutions in mixed Cu(II) complexes derived from stereolabile biphenyl-2,2′-diol and enantiopure 1,2-diamines have been achieved by crystallization. In these cases, all 2,2′-disubstituted biphenyl fragments in the crystal have the same configuration at the stereogenic axis as a result of the transmission of chirality at the molecular level from the chiral inducer (enantiopure diamine ligand) to the dynamically racemic biaryl units by means of supramolecular forces (metal−ligand and hydrogen bonding interactions). Stereoselective synthetic strategies toward [Cu(2,2′-biphenolate)(1,2-diamine)] complexes have been developed, and these derivatives have been characterized and studied by X-ray diffraction. The formation of hydrogen bonds in an intramolecular (between the biphenyl-2,2′-diol and diamine moieties) and in an intermolecular (between the moieties of the copper complex and cocrystallized methanol) way appears to be essential for the induction of chirality.

T

scarce in the literature. In the few cases that have been reported, fast atropisomerization of polycyclic derivatives or fast rotation around Caryl−Caryl bonds followed by hydrogen-bonddriven selective crystallization leads to nonracemic compounds or aggregates.7 Within our ongoing project aimed at controlling molecular handedness via supramolecular interactions (hydrogen−bonding and Zn(II)-coordination chemistry),8 we also turned our attention to the use of copper-ligand interactions to achieve this goal. Thus, we wish to report here our preliminary results on the induction of axial chirality in dynamically racemic biaryls by the formation of mixed [Cu(2,2′-biphenolate)(1,2-diamine)] complexes. Coordination studies with the aim of obtaining mixed [Cu(2,2′-biphenolate)(1,2-diamine)] complexes were carried out according to two distinct methods: (i) sequential complexation of a copper precursor with enantiomerically pure diamine 49 in aqueous methanol followed by reaction with deprotonated biphenyl-2,2′-diol generated with NaOH (Na-2,10 method A; Scheme 1), and (ii) a closely related strategy using biphenyl-2,2′-diolate Li2-3 generated with n-BuLi as the base11 (method B; Scheme 1). Studies were carried out with commercially available biphenyl-2,2′-diol (1) and enantiopure cyclohexane-1,2-diamine [(1R,2R)-cyclohexane-1,2-diamine (4) and its enantiomer].

he manipulation of chirality at the molecular level is an important research field that is immediately applicable to asymmetric synthesis, chiral recognition, and chirogenesis, among other applications.1 While the manipulation of molecular chirality using covalent chemistry is already a wellestablished methodology, the use of supramolecular interactions to control molecular handedness is a field that is rapidly maturing and is already allowing the stereoselective preparation of complex chiral architectures with exquisite detail. Chemists have elegantly used reversible interactions (mainly hydrogenbonding and metal−ligand interactions) not only to generate the backbones of a myriad of chiral molecules by bringing together enantiopure building blocks2 but also to form a given stereoisomer preferentially as a result of the influence of a chiral bias.3 Chirality induction strategies that involve supramolecular interactions mostly rely on dynamic stereochemistry:4 that is, a mixture of rapidly interconverting enantiomers that is disrupted from equilibrium by a chiral bias. This manuscript details our preliminary investigations into the use of a related strategy aimed at the induction of axial chirality in stereolabile atropisomeric biaryls. Crystallization-induced dynamic resolution (CIDR) has proven to be a very practical and efficient asymmetric transformation, in which labile substrates are transformed by a dynamic resolution followed by selective crystallization into optically pure compounds.5 While this strategy has been efficiently exploited using standard covalent chemistry,6 reports on CIDR using supramolecular interactions on stereolabile substrates are, to the best of our knowledge, © 2012 American Chemical Society

Received: January 12, 2012 Revised: April 16, 2012 Published: April 17, 2012 2719

dx.doi.org/10.1021/cg300044v | Cryst. Growth Des. 2012, 12, 2719−2723

Crystal Growth & Design

Communication

Scheme 1. Preparation of Cu(II) Complexes 5 and 7 (Dotted Lines Indicate Contacts)

Figure 1. ORTEP plot of complex 5 showing a view perpendicular to and along the O1···Cu1···O3 axis. Ellipsoids are at the 50% probability level; thin dashed lines indicate hydrogen bonds. Hydrogen atoms were calculated on the chemically expected positions and refined, fixed on the corresponding atoms, except hydrogen atoms from OH groups, which were refined allowing to ride on the immediately preceding O atom and to rotate about the C−O bond.

biphenyl groups is not deprotonated;10 see Scheme 1). The molecular structure of 5, as determined by X-ray analysis, differs from the one reported by Patel and Trivedi,9 who previously used the same synthetic strategy to synthesize a 1:1 biaryl-2,2′diol/diamine copper-chelate using other starting materials (instead of a 2:2 biaryl-2,2′-diol/diamine complex as in 5). On using n-BuLi as the deprotonating agent, biphenyl-2,2′diol (1) was converted into its dianion Li2-3. This derivative was sequentially transformed into [Cu(biphenyl-2,2′-diolate)] (6) and finally into the mixed dinuclear [{Cu(biphenyl-2,2′diolate)(1,2-diamine)}2] complex 7 (see Scheme 1 for the structure and the Supporting Information for details). The structure of the [Cu(2,2′-biphenolate)(1,2-diamine)] complexes obtained by following either method A or B is not the only difference between the two methods. A preferential sense of axial rotation was not induced in the biaryl units of complex 7 on using enantiopure diamine 4, but both 2′-hydroxy-[1,1′-biphenyl]-2-olate

Regarding the formation of mixed [Cu(2,2′-biphenolate) (1,2-diamine)] complexes by method A, a solution of the deprotonated biphenyl-2,2′-diol10 was slowly added to a mixture of the diamine 4 and copper(II) chloride dihydrate in H2O/MeOH (1:1). A color change from dark blue to grayish-blue and finally to green/brown was accompanied by precipitation of a colored byproduct. Removal of the precipitate12 and the NaCl formed in the reaction gave a filtrate from which compound 5 was isolated as purple platelike crystals.13 X-ray analysis of this crystalline material enabled the structure of the complex to be determined (see Figure 1). The Cu(II) center was found to be ligated by two diamine moieties (Cu−N distances = 2.01−2.03 Å; entries 1−4 in Table 1). Two contacts with two biphenyl groups via a phenolate oxygen atom (Cu···O contacts = 2.56−2.63 Å; entries 5 and 6 in Table 1) are present and complete a distorted octahedral geometry at the copper center (the second phenol function in each of the two 2720

dx.doi.org/10.1021/cg300044v | Cryst. Growth Des. 2012, 12, 2719−2723

Crystal Growth & Design

Communication

Table 1. Selected Bond Lengths (Å), Bond Angles (deg), and H-Bond Lengths (Å) for Complex 5 entry

atom 1

atom 2

1 2 3 4 5 6

Cu1 Cu1 Cu1 Cu1 Cu1 Cu1

N1 N2 N3 N4 O1 O3

7 8 9 10 11

N1 N3 N3 O3 N3

Cu1 Cu1 Cu1 Cu1 Cu1

12 13 14 15 16 17 18 19

O2 O4 O1 O3 N1 N3 O1M O1N

N4 N2 O2 O4 O1M O1N O4 O2

atom 3

length 2.0131(18) 2.034(2) 2.010(2) 2.0303(18) 2.6333(19) 2.563(2) angle

N2 N1 N2 O1 O1

84.82(7) 95.28(8) 173.53(9) 178.43(6) 92.66(7) H-bond lengtha 2.971(2)b 3.005(2)c 2.463(3)d 2.452(3)e 2.919(2)f 2.901(3)g 2.663(3)h 2.671(3)i

Figure 2. Hydrogen-bond mediated 3D-network in 5 (thin dashed lines indicate hydrogen bonds). Crystal packing shown with view along the C-axis of the unit cell.

a Defined as the distance between heteroatoms. bO2···H−N4: 2.16 Å uncorrected. cO4···H−N2: 2.18 Å uncorrected. dO1···H: 1.65 Å uncorrected. eO3···H: 1.63 Å uncorrected. fO1M···H−N1: 2.01 Å uncorrected. gO1N···H−N3: 2.00 Å uncorrected. hO4···H−O1M: 1.83 Å uncorrected. iO2···H−O1N: 1.83 Å uncorrected.

units remarkably adopted a preferential axial sense of rotation in complex 5, namely Ra (θ ≈ −42°) with diamine 4.14 The combination of copper−ligand interactions together with the formation of intra- and intermolecular hydrogen bonds appears to be responsible for the induction of chirality. The amino groups of the diamine are bound to the copper center and serve as rigid anchoring points for the hydrogen bond network. Both phenol groups establish intramolecular hydrogen bonds (based on the O···N distances, entries 12 and 13 in Table 1) with one of the coordinated amino groups of the diamine. Intermolecular hydrogen bonds from the free amino groups to cocrystallized methanol molecules [see the connectivity of N1 with O1M and of N3 with O1N in Figure 1 and the corresponding distances in entries 16 and 17 in Table 1] and from these cocrystallized methanol molecules to phenol groups located in adjacent crystal cells (see the corresponding distances in entries 18 and 19 in Table 1) complete the network (see Figure 2). In addition, intramolecular hydrogen bonds were found in both 2′-hydroxy-[1,1′-biphenyl]-2-olate units between the atoms O1···H−O2 and O3···H−O4. These hydrogen bonds in the biaryl units are stronger and shorter than the ones from the phenol and amino groups (compare entries 12 and 13 with entries 14 and 15 in Table 1). We considered the possibility that a crystallization-induced dynamic resolution (CIDR) process could have occurred during the formation of mixed mononuclear [Cu(2′-hydroxy[1,1′-biphenyl]-2-olate)(1,2-diamine)] complex 5. To investigate this possibility, we studied the homogeneity of the batch of 5 from which the single crystal was picked. The powder diffraction pattern was recorded and was found to be in very good agreement with the pattern calculated from the single crystal structure (Figure 3), which ultimately indicates that the

Figure 3. Powder X-ray diffraction patterns of Cu(II) complexes 5 and 8.

major crystalline material present in the batch of 5 corresponds to the structure of the measured single crystal.15 For CIDR to be successful, the rate of inversion of biphenyl2,2′-diol derivatives must be faster than the rate of crystallization. This is obviously the case in our system, as 2,2′-disubstituted biaryl derivatives freely rotate around the Caryl−Caryl bond at the crystallization temperature (−18 °C),16 while crystallization of 5 took a few hours. Furthermore, we were able to prove that complex 5 or ent-514 corresponds to the kinetic product of the reaction between diamine 4 or ent-4, respectively, and deprotonated biphenyl-2,2′-diol, thus reaffirming that the whole process is kinetically driven. On leaving crystals of ent-5 to stand in the mother liquor at −18 °C for several weeks, this compound evolved to a new copper complex 8 (Scheme 2).17 X-ray analysis revealed that changes in the overall connectivity had not occurred with respect to complex ent-5 but that the preferential sense of axial rotation of the 2721

dx.doi.org/10.1021/cg300044v | Cryst. Growth Des. 2012, 12, 2719−2723

Crystal Growth & Design

Communication

Scheme 2. Racemization of the 2′-Hydroxy-[1,1′-biphenyl]-2-olate Ligands in Compound ent-5 (Dotted Lines Indicate Contacts)

■

ACKNOWLEDGMENTS We thank MICINN (Grant CTQ2011-28512), DURSI (Grant 2009SGR623), and the ICIQ Foundation for financial support. H.D. and A.-S.F. acknowledge the “Programa FPU” (Grant AP2006-04169) and the “Programa Torres Quevedo” for financial support, respectively.

2′-hydroxy-[1,1′-biphenyl]-2-olate groups was lost in the new product 8, since the unit cell contains two independent copper complexes with opposite senses of axial rotation of the 2′hydroxy-[1,1′-biphenyl]-2-olate moieties (see Scheme 2 for the structure and the Supporting Information for an ORTEP plot). These results ultimately indicate that the kinetically formed product ent-5 is transformed, probably by slow dissolution of its crystals in the mother liquor, into a more stable product 8, which should be regarded as an aggregate in the solid state of two diastereomeric Cu(II) complexes. In conclusion, the 2′-hydroxy-[1,1′-biphenyl]-2-olate moieties in mixed Cu(II) complexes 5 and ent-5, derived from the aforementioned stereolabile diols and enantiopure 1,2diamines, crystallize as highly ordered structures due to the influence of the enantiopure amino fragments on the preferred sense of axial rotation of the Caryl−Caryl bond. The same absolute configuration at the stereogenic axis can be induced in all 2′-hydroxy-[1,1′-biphenyl]-2-olate fragments in the crystal through a CIDR (crystallization-induced dynamic resolution) process by choosing suitable reaction conditions (i.e., base and solvent employed to deprotonate the biphenyl-2,2′-diol). This work shows the potential of metal−ligand interactions for the transfer and control of chirality at the molecular level: a chirally oriented conformation can be created from stereolabile compounds by the stereogenic elements of a chiral inducer present in the molecule. The formation of this kind of mixed [Cu(2,2′-biphenolate)(1,2-diamine)] complexes constitutes one of the few reported examples of dynamic resolution of tropos biaryl derivatives involving supramolecular interactions (i.e., metal−ligand and hydrogen-bonding interactions). Work is in progress to extend this strategy to other enantiopure amines and stereolabile biaryl derivatives and to exploit this approach in crystal engineering and chiral ligands for asymmetric transformations of interest.

■

■

(1) See the following general references and those cited therein: (a) In Comprehensive Asymmetric Catalysis, 1st ed.; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Heidelberg, 1999; Vols. I− III. (b) In Comprehensive Asymmetric Catalysis: Supplements I and II, 1st ed.; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; SpringerVerlag: Heidelberg, 2004. (c) Borovkov, V. V.; Hembury, G. A.; Inoue, Y. Acc. Chem. Res. 2004, 37, 449. (d) Ernst, K.-H. Top. Curr. Chem. 2006, 265, 209. (e) Hembury, G. A.; Borovkov, V. V.; Inoue, Y. Chem. Rev. 2008, 108, 1. (f) Szumna, A. Chem. Soc. Rev. 2010, 39, 4274. (2) See the following general references and those cited therein: (a) Lee, S. J.; Lin, W. Acc. Chem. Res. 2008, 41, 521. (b) Ballester, P.; Vidal-Ferran, A. In Supramolecular Catalysis; van Leeuwen, P. W. N. M., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2008; p 1. (c) Meeuwissen, J.; Reek, J. N. H. Nat. Chem. 2010, 2, 615. (d) Ballester, P.; Vidal-Ferran, A.; van Leeuwen, P. W. N. M. In Modern Strategies in Supramolecular Catalysis; Gates, B. C., Knözinger, H., Jentoft, F., Eds.; Advances in Catalysis; Academic Press: U.K., 2011; Vol. 54, pp 63−126. (3) See for example: (a) Costa, A. M.; Jimeno, C.; Gavenonis, J.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124, 6929. (b) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem. Rev. 2003, 103, 3297. (c) Borovkov, V. V.; Hembury, G. A.; Inoue, Y. Angew. Chem., Int. Ed. 2003, 42, 5310. (d) Kubo, Y.; Ishii, Y.; Yoshizawa, T.; Tokita, S. Chem. Commun. 2004, 1394. (e) de Jong, J. J. D.; Lucas, L. N.; Kellogg, R. M.; van Esch, J. H.; Feringa, B. L. Science 2004, 304, 278. (f) Eelkema, R.; Feringa, B. L. J. Am. Chem. Soc. 2005, 127, 13480. (g) Hou, J.-L.; Yi, H.-P.; Shao, X.-B.; Li, C.; Wu, Z.-Q.; Jiang, X.-K.; Wu, L.-Z.; Tung, C.-H.; Li, Z.-T. Angew. Chem., Int. Ed. 2006, 45, 796. (h) Takagi, H.; Mizutani, T.; Horiguchi, T.; Kitagawa, S.; Ogoshi, H. Org. Biomol. Chem. 2005, 3, 2091. (i) Ikeda, C.; Yoon, Z. S.; Park, M.; Inoue, H.; Kim, D.; Osuka, A. J. Am. Chem. Soc. 2005, 127, 534. (j) Ishii, Y.; Soeda, Y.; Kubo, Y. Chem. Commun. 2007, 2953. (k) Etxebarria, J.; Vidal-Ferran, A.; Ballester, P. Chem. Commun. 2008, 5939. (l) Haino, T.; Tanaka, M.; Fukazawa, Y. Chem. Commun. 2008, 468. (m) Etxebarria, J.; Degenbeck, H.; Felten, A. S.; Serres, S.; Nieto, N.; Vidal-Ferran, A. J. Org. Chem. 2009, 74, 8794. (n) Wezenberg, S. J.; Salassa, G.; Escudero-Adan, E. C.; Benet-Buchholz, J.; Kleij, A. W. Angew. Chem., Int. Ed. 2011, 50, 713. (o) Huang, Z.; Kang, S.-K.; Lee, M. J. Mater. Chem. 2011, 21, 15327. (4) See for example: Wolf, C. Dynamic Stereochemistry of Chiral Compounds: Principles and Applications; The Royal Society of Chemistry: Cambridge, U.K., 2008. (5) See the following references for reviews on this topic: (a) Caddick, S.; Jenkins, K. Chem. Soc. Rev. 1996, 25, 447. (b) Ebbers, E. J.; Ariaans, G. J. A.; Houbiers, J. P. M; Bruggink, A.; Zwanenburg, B.

ASSOCIATED CONTENT

S Supporting Information *

Crystal data, ORTEP plots, and CIF files of complexes 5, ent-5, 7, and 8. This material is available free of charge via the Internet at http://pubs.acs.org.

■

REFERENCES

AUTHOR INFORMATION

Corresponding Author

*Phone: +34 977 920 210. Fax: +34 977 920 228. E-mail: [email protected]. Notes

The authors declare no competing financial interest. 2722

dx.doi.org/10.1021/cg300044v | Cryst. Growth Des. 2012, 12, 2719−2723

Crystal Growth & Design

Communication

Tetrahedron 1997, 53, 9417. (c) Anderson, N. G. Org. Process Res. Dev. 2006, 10, 683. (6) See for example: (a) Kosmrlj, J.; Weigel, L. O.; Evans, D. A.; Downey, C. W.; Wu, J. J. Am. Chem. Soc. 2003, 125, 3208. (b) Chen, J. G.; Zhu, J.; Skonezny, P. M.; Rosso, V.; Venit, J. J. Org. Lett. 2004, 6, 3233. (c) Kiau, S.; Discordia, R. P.; Madding, G.; Okuniewicz, F. J.; Rosso, V.; Venit, J. J. J. Org. Chem. 2004, 69, 4256. (d) Marchalin, S.; Cvopova, K.; Kriz, M.; Baran, P.; Oulyadi, H.; Daich, A. J. Org. Chem. 2004, 69, 4227. (e) Xu, H.-W.; Wang, Q.-W.; Zhu, J.; Deng, J.-G.; Cun, L.-F.; Cui, X.; Wu, J.; Xu, X.-L.; Wu, Y.-L. Org. Biomol. Chem. 2005, 3, 4227. (f) Ikunaka, M.; Kato, S.; Sugimori, D.; Yamada, Y. Org. Process Res. Dev. 2007, 11, 73. (g) Yanagisawa, A.; Nishimura, K.; Ando, K.; Nezu, T.; Maki, A.; Kato, S.; Tamaki, W.; Imai, E.; Mohri, S.I. Org. Process Res. Dev. 2010, 14, 1182. (7) (a) Herradon, B.; Montero, A.; Mann, E.; Maestro, M. A. CrystEngComm 2004, 6, 512. (b) Altamura, M.; Guidi, A.; Jierry, L.; Paoli, P.; Rossi, P. CrystEngComm 2011, 13, 2310. (8) See ref 3m for hydrogen bonding mediated control of axial chirality in stereolabile biaryls. The work published in ref 3k and other unpublished results encompass application of zinc coordination chemistry to control molecular handedness. (9) Patel, M. J.; Trivedi, B. M. J. Chem. Res. 2004, 198. (10) The extent of deprotonation of biphenyl-2,2′-diol (1) and NaOH in MeOH/H2O 1:1 was determined by speciation analysis. The ratio of 1, Na-2, and Na2-3 was predicted at different pH values using SpecFit (see Supporting Information for details) and considering reported values of pK1 = 7.6 and pK2 = 13.7 for 1 in H2O (taken from: Jonsson, M.; Lind, J.; Merényi, G. J. Phys. Chem. A 2002, 106, 4758 ). The pH value of the solutions of 1 used for the synthesis of the desired copper complexes was measured to be 12.35, which indicates 2σ(Fo) and 405 parameters. (14) The enantiomer of complex 5 (ent-5) was prepared by following method A from biphenyl-2,2′-diol (1) and (1S,2S)-cyclohexane-1,2diamine (ent-4). As expected, an inverse sense of axial rotation [Sa (θ ≈ 42°)] was observed in this case. See the Supporting Information for the crystallographic data for ent-5. (15) The theoretical diffraction pattern was calculated from the crystal data using the program Mercury 2.3. The fact that the theoretical phase appears slightly shifted arises from measuring the powder diffraction

pattern at room temperature and comparing the experimental data with a calculated set from a crystal structure that was measured at 100 K. (16) The minimum energy required for the enantiomerization of biphenyl-2,2′-diol (1) was estimated by DFT calculations to be ca. 11 kcal·mol−1: Sahnoun, R.; Koseki, S.; Fujimura, Y. J. Phys. Chem. A 2006, 110, 2440. (17) Complex 8 was also obtained by following the experimental procedure indicated in ref 13, but with the crude material in MeOH heated under reflux for 30 min.

2723

dx.doi.org/10.1021/cg300044v | Cryst. Growth Des. 2012, 12, 2719−2723