Supporting Information. Synthesis, resolution and absolute configuration of chiral 4,4 -bipyridines

Transcription

1 Supporting Information Synthesis, resolution and absolute configuration of chiral 4,4 -bipyridines Victor Mamane,* a Emmanuel Aubert, b Paola Peluso, c and Sergio Cossu d a Laboratoire SRSMC UMR CRS 7565, ancy Université, 5456 Vandoeuvre-les-ancy, France. b Laboratoire CRM 2 UMR CRS 736, ancy Université, 5456 Vandoeuvre-les-ancy, France. c Institute of Biomolecular Chemistry, UOS of Sassari, C..R., 71 Sassari, Italy. d Dipartimento di Scienze Molecolari e anosistemi, Università Ca' Foscari Venezia, 3123 Venezia, Italy. COTET victor.mamane@srsmc.uhp-nancy.fr Copies of MR spectra of compounds 2-5 S-2 ECD spectrum of 5b-M S-13 Details on the XRD analyses S-14 Details on the theoretical calculations S-16 - Energy barriers of racemisation S-16 - Comparison of experimental and calculated ECD spectra S-4 S-1

2 S-2 Br Br ppm (t1) ppm (t1)

3 1 Br I 3 2 I Br ppm (t1) ppm (t1) S-3

4 S-4 4a ppm (t1) ppm (t1) Br Br

5 S-5 4b ppm (t1) ppm (t1) Br Br MeO OMe

6 S-6 4c ppm (t1) ppm (t1) Br Br OMe MeO

7 S-7 4d ppm (f1) ppm (f1) Br Br Cl Cl

8 Br 4e 8 9 Br ote: MR analysis shows the presence in small amount of a minor conformer (about 8% according to the peak integration). Indeed, the GC analysis shows only one product. The presence of two conformers is expected due to the rotation along the aphtyl Pyridine bond. S-8

9 S-9 ppm (t1) ppm (t1)

10 S-1 4f ppm (t1) ppm (t1) Br Br

11 S-11 5a ppm (t1) ppm (t1) Br Br

12 S-12 5b ppm (t1) ppm (t1) Br Br Fe Cp Fe

13 ECD spectrum of 5b-M S-13

14 Details on the XRD analyses: Bipyridine 2 ORTEP plot of 2. Thermal ellipsoids set at 5% probability and hydrogen atoms shown as sticks. Bipyridine 3 The crystal structure of 3 (2 nd eluted peak) was solved in P1 space group. The Flack parameter introduced as an inversion twin population refined to.269(6), the absolute configuration being P. The R 1 values were.496 (I > 2σ(I)) and.538 (all data). The wr(f 2 ) values were.1481 (I > 2σ(I)) and.1522 (all data). The goodness of fit on F 2 was 1.2. In this model three of the four crystallographically independent molecules, display C-Halogen bonds lengths in between C-Br (1.89Å) and C-I (2.9Å) bond lengths; moreover, corresponding bromine atoms display relative small atomic displacement parameters whereas iodine atoms display relative large ADP values. This indicates that three of these four molecules are disordered. The final model is then built by considering that these three sites are occupied by 3-P molecules having different orientations; the validity of this model is assessed by the significant decrease of the wr(f 2 ) value (the final wr(f 2 ) values were.685 (I > 2σ(I)) and.77 (all data)). The final Flack parameter (i.e. inversion twin population) is not zero (.124(5).) and indicates a small enantiomeric M contamination, as an enantiomorphous crystal phase. However, since the crystal is disordered, the standard uncertainty on this Flack parameter is certainly larger than the value obtained. S-14

15 Bipyridine 4a ORTEP plot of 4a. Thermal ellipsoids set at 5% probability and hydrogen atoms shown as sticks. Bipyridine 5b ORTEP plot of 5b (2 nd eluted peak). The axial configuration is P. Thermal ellipsoids set at 5% probability and hydrogen atoms shown as sticks. S-15

16 Details on the theoretical calculations All calculations were performed using the Gaussian9 Rev. B.1 program package (Frisch et al., 21). Energy barriers of racemisation Molecular structures of bipyridines and their relative transitions states of racemisation were optimized at the DFT level of theory using the B97D functional including dispersion correction. The basis set employed was cc-pvdz on all elements, and effective core potentials were used to model atomic cores of Bromine and Iodine atoms (Peterson et al., 23; Schuchardt et al., 27). Solvent effects (methanol) were taken into account through the polarisable continuum model. Vibration frequencies were computed for the ground states and the transition states (ultra fine grids were used). In the later case, it was checked that the imaginary frequencies transform the transition states structures toward the P and M enantiomers. Results are summarized in the Table below: Compound G TS1 a ν b G TS2 a ν b T c r a b c d e a a Standard free energy of activation (T=298.15K), in Kcal.mol -1. b Imaginary vibration frequencies computed at the TS geometry, displayed as negative number in cm -1 c Racemisation temperature (T r, in C) as solution of the non-linear equation: ln(2)/t r =(k B.T r /h).exp(- G /(R.T r )), where k B is the Boltzmann constant, h the Planck constant and R the ideal gas constant. Optimized molecular structures of ground (M enantiomers) and transition states TS1 & TS2 (color scheme: grey: carbon, blue: nitrogen, white: hydrogen, brown: bromine, magenta: iodine, red: oxygen, green: chlorine) 3 ground state M-enantiomer, TS1, TS2: S-16

17 4a ground state M-enantiomer, TS1, TS2: 4b ground state M-enantiomer, TS1, TS2: S-17

18 4c ground state M-enantiomer, TS1, TS2: 4d ground state M-enantiomer, TS1, TS2: S-18

19 4e ground state M-enantiomer, TS1, TS2: 5a ground state M-enantiomer, TS1, TS2: S-19

20 Atomic coordinates and absolute energies (T=298.15K) of 3: ground state C C C C C H H C C C C C H H Br Br I I Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy=.6335 Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 3: Transition State 1 C C C C C H H C C C C C H H Br Br I I S-2

21 Zero-point correction=.1969 (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 3: Transition State 2 C C C C C H H C C C C C H H Br Br I I Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4a: ground state Br C H C C H C C C C H C H S-21

22 C H C H C H Br C H C C H C C C C H C H C H C H C H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4a: Transition State 1 Br C H C C H C C C C H C H C H C H C H Br S-22

23 C H C C H C C C C H C H C H C H C H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4a: Transition State 2 Br C H C C H C C C C H C H C H C H C H Br C H C C H C C C S-23

24 C H C H C H C H C H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4b: ground state Br C H C C H C C C C H C H C C H C H Br C H C C H C C C C H C H C C H C S-24

25 H O O C H H H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4b: Transition State 1 Br C H C C H C C C C H C H C C H C H Br C H C C H C C C C H C H C C H S-25

26 C H O O C H H H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4b: Transition State 2 Br C H C C H C C C C H C H C C H C H Br C H C C H C C C C H C H C C H S-26

27 C H O O C H H H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4c: ground state Br C C C H C C C C H C H C C H C H Br C C C H C C C C H C H C C H C S-27

28 H H H O O C H H H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4c: Transition State 1 Br C C C H C C C C H C H C H C H C H Br C C C H C C C C H C H C H S-28

29 C H C H O O C H H H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4c: Transition State 2 Br C H C C H C C C C H C C H C H C H Br C C C H C C C C H C H C S-29

30 H C H C H O O C H H H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4d: ground state Br C H C C H C C C C H C H C C H C H Br C H C C H C C C C H C H S-3

31 C C H C H Cl Cl Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4d: Transition State 1 Br C H C C H C C C C H C H C C H C H Br C H C C H C C C C H C H C C H C H Cl Cl S-31

32 Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4d: Transition State 2 Br C H C C H C C C C H C H C C H C H Br C H C C H C C C C H C H C C H C H Cl Cl Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= S-32

33 Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4e: ground state Br C C H C C C H Br C C H C C C H C C C C C C H C H C C H C H H H H C C C C C C H C H C C H C H H H H Zero-point correction= (Hartree/Particle) S-33

34 Thermal correction to Energy=.4962 Thermal correction to Enthalpy=.417 Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4e: Transition State 1 Br C C H C C C H Br C C H C C C H C C C C C C H C H C C H C H H H H C C C C C C H C H C C H C H H S-34

35 H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy=.4779 Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 4e: Transition State 2 Br C C H C C C H Br C C H C C C H C C C C C C H C H C C H C H H H H C C C C C C H C H C C S-35

36 H C H H H H Zero-point correction=.3865 (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 5a: ground state Br C C H C C C H Br C C H C C C H C C C C C C C C H C H C H H H C C C C H C H C S-36

37 H H H Zero-point correction=.3915 (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 5a: Transition State 1 C C C C C H C C C C C Br C C Br H H H C C C C C C H C H C H H H C C C C H C H C H H H S-37

38 Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Atomic coordinates and absolute energies (T=298.15K) of 5a: Transition State 2 C C C C C H C C C C C Br C C Br H H H C C C C C C H C H C H H H C C C C H C H C H H H Zero-point correction= (Hartree/Particle) Thermal correction to Energy= Thermal correction to Enthalpy= S-38

39 Thermal correction to Gibbs Free Energy= Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= S-39

40 Electronic circular dichroism calculations Molecular structures were first optimized at the DFT level of theory, using the CAM-B3LYP functional and the G(d,p) basis set for all elements. Solvent effects (methanol) were taken into account through the polarisable continuum model. Rotational strengths were then calculated on the converged molecular structures at the TD-DFT level of theory, using the same functional and basis sets. In these calculations, solvent effects were taken into account in the non-equilibrium formalism. ECD spectra were finally obtained as superposition of Gaussian functions (half-height width set to.25ev) centred on the previously determined absorption wavelengths. Results are reported in Fig. 1 to 6, where data are given as ε in L.mol -1.cm -1. As can been seen in comparison to experimental data, theoretical ECD spectra are systematically shifted to shorter wavelengths, as noticed in previous studies (Pipolo et al., 211). References Peterson, K.A., Figgen, D., Goll, E., Stoll, H. and Dolg, M. J. Chem. Phys. 23, 119, Schuchardt, K.L., Didier, B.T., Elsethagen, T., Sun, L., Gurumoorthi, V., Chase, J., Li, J., and Windus, T.L. J. Chem. Inf. Model. 27, 47, 145. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. akatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. akajima, Y. Honda, O. Kitao, H. akai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K.. Kudin, V.. Staroverov, T. Keith, R. Kobayashi, J. ormand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi,. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and D. J. Fox, Gaussian, Inc., Wallingford CT, 21. Pipolo, S., Percudani, R., Cammi, R. Org. Biomol. Chem. 211, 9, S-4

41 Fig. 1 Comparison of experimental (black triangles, 1 st peak in chiral HPLC) and theoretical (squares) ECD spectra of 4a-M enantiomer. Fig.2 Comparison of experimental (black triangles, 1 st peak in chiral HPLC) and theoretical (squares) ECD spectra of 4c-M enantiomer. Fig. 3 Comparison of experimental (black triangles, 2 nd peak in chiral HPLC) and theoretical (squares) ECD spectra of 4d-M enantiomer. S-41

42 Fig. 4 Comparison of experimental (black triangles, 1 st peak in chiral HPLC) and theoretical (squares) ECD spectra of 4e-M enantiomer. Fig. 5 Comparison of experimental (black triangles, 1 st peak in chiral HPLC) and theoretical (squares) ECD spectra of 4f-M enantiomer. Fig. 6 Comparison of experimental (black triangles, 1 st peak in chiral HPLC) and theoretical (squares) ECD spectra of 5a-M enantiomer. S-42