Homologation of Boronic Esters with Organolithium Compounds: A Computational Assessment of Mechanism

Size: px

Start display at page:

Download "Homologation of Boronic Esters with Organolithium Compounds: A Computational Assessment of Mechanism"

Vivian Cross
5 years ago
Views:

1 Homologation of Boronic Esters with Organolithium Compounds: A Computational Assessment of Mechanism Stéphanie Essafi,*,1 Simone Tomasi, 2 Varinder K. Aggarwal, 1 Jeremy Harvey*,1 1 School of Chemistry, University of Bristol, Cantock s Close, Bristol, BS8 1TS, U.K. 2 AstraZeneca, Pharmaceutical Development, Charter Way, Macclesfield, Cheshire SK10 2NA Additional Computational Details... 2 Additional Discussion... 3 Sample Molpro Files... 6 Energies and Frequencies... 8 Cartesian coordinates

2 Additional Computational Details Coupled-cluster calculations were performed using the Molpro package. 1 A density-fitted local correlation treatment 2 was used all along. For the composite method, local coupled-cluster calculations as well as local MP2 calculations were performed. In the latter case, additional calculations using explicit treatment of electron-electron correlation (F12 method) were performed in order to approach the infinite basis set limit and correct for domain effects. The specially optimized correlation consistent VDZ-F12 basis set 3 was used for the LMP2-F12 (ansatz = 3*A(loc)) calculations 4 along with a suitable combination of auxiliary basis sets (see below for a sample input file). The aug-cc-pvdz (AVDZ) basis set was used for LMP2 and LCCSD(T0) calculations along with a similar combination of auxiliary basis sets (see below for a sample input file). The valence orbitals were localized using the Pipek-Mezey procedure. The orbital domains were determined automatically using the procedure of Boughton and Pulay along with the default completeness criterion of In order to improve the localization, contribution of the two most diffuse basis function of each angular momentum was removed (keyword pipek,delete=2) in LMP2 and LMP2-F12 calculations. Composite electronic energies at the LCCSD(T0)-F12 level of theory were estimated as: ( ) The first term corresponds to the DF-LMP2-F12 energy. The difference between the two remaining terms introduces higher-order correlation effects through coupled cluster calculations. In these calculations, strong pairs are treated at the CCSD level whereas weak and distant pairs are treated at the MP2 level. 1 (a) MOLPRO, version , a package of ab initio programs, H.-J. Werner, P. J. Knowles, G. Knizia, F. R. Manby, M. Schütz, P. Celani, T. Korona, R. Lindh, A. Mitrushenkov, G. Rauhut, K. R. Shamasundar, T. B. Adler, R. D. Amos, A. Bernhardsson, A. Berning, D. L. Cooper, M. J. O. Deegan, A. J. Dobbyn, F. Eckert, E. Goll, C. Hampel, A. Hesselmann, G. Hetzer, T. Hrenar, G. Jansen, C. Köppl, Y. Liu, A. W. Lloyd, R. A. Mata, A. J. May, S. J. McNicholas, W. Meyer, M. E. Mura, A. Nicklass, D. P. O'Neill, P. Palmieri, D. Peng, K. Pflüger, R. Pitzer, M. Reiher, T. Shiozaki, H. Stoll, A. J. Stone, R. Tarroni, T. Thorsteinsson, and M. Wang,, see (b) Werner, H.-J., Knowles, P. J., Knizia, G., Manby, F. R., Schütz, M. Molpro: a general-purpose quantum chemistry program package. WIREs Comput. Mol. Sci. 2, (2012). 2 Adler, T. B., Werner, H.-J. & Manby, F. R. Local explicitly correlated second-order perturbation theory for the accurate treatment of large molecules. J. Chem. Phys. 130, (2009). 3 For VnZ-F12 basis sets: Peterson, K. A., Adler, T. B. & Werner, H.-J. Systematically convergent basis sets for explicitly correlated wavefunctions: The atoms H, He, B Ne, and Al Ar. J. Chem. Phys. 128, (2008). For auxiliary basis: Yousaf, K. E. & Peterson, K. A. Optimized auxiliary basis sets for explicitly correlated methods. J. Chem. Phys. 129, (2008). 4 Werner, H.-J. Eliminating the domain error in local explicitly correlated second-order Møller Plesset perturbation theory. J. Chem. Phys. 129, (2008). 2

Triple excitations were treated perturbatively using the (T0) approximation. Integral direct algorithms were used as recommended for large molecules.

3 Triple excitations were treated perturbatively using the (T0) approximation. Integral direct algorithms were used as recommended for large molecules. Additional Discussion It is interesting to cross-check the methodology used for computing relative potential energies by considering the relative free energies for all the conformers of 4a as predicted by three different methods, see Figure S1. Though the order in relative free energies of different conformers with different methods is broadly conserved, there is a systematic difference in the magnitude of these values, as already discussed above. B3LYP-D2 systematically overestimates the exoergicity of formation of the ate complex. LCCSD(T0)-F12 values lie between 6 and 13 kcal mol 1 above the B3LYP-D2 ones, while the B3LYP- D3 values are intermediate. There is a considerable spread in the differences between the values obtained with different methods. Figure S1. Free energies (kcal mol 1 ) computed for various conformers of 4a with respect to separated reactants. The level of theory refers to electronic energies only. Entropic and bulk solvent contributions were estimated at the B3LYP-D2/6-31+G(d) level of theory. 3

4 Scheme S1. Conformational analysis of the ate complex 4b. Gibbs free energies in solution (Et 2 O) computed at the LCCSD(T0)-F12/VDZ-F12//B3LYP-D2/6-31+G(d) level of theory (see text for details) and given with respect to the separated reactants MeBpin + Me 2 CLiOCb.2Me 2 O. A conformational analysis has been performed for 4b, though here only disolvated structures were considered based on the analysis for 4a and inspection of the structures to be favoured (Figure S1). Initial structures were generated from conformers of 4a by simply replacing the H atom with a methyl group. The five most stable conformers of 4a (A, B, G, H and I) as well as the conformer C were used. The latter was optimized for comparison purposes only. As for 4a, C-2solv is found to be strongly disfavoured, lying more than 20 kcal mol 1 above the lowest conformer. This again highlights the importance of the lithium-pinacol interaction. Despite the fact that the ate complex 4b is symmetric (neglecting the counter-cation), it is interesting to note that the conformers A and B do not have the same free energy ( -2.1 kcal mol 1 and kcal mol 1 respectively). These two conformers might be expected to be equivalent upon cursory inspection, but in fact when started from input geometries generated from 4a, different structures were obtained. A-2solv displays an additional lithium-ch 3 interaction with the migrating group (Li O pinacol = Å; Li H terminus = Å; Li H migrating = Å; Li O carbamate = Å and Li O solvent = / Å) which is absent in B-2solv. The 4

5 same is true for the pair of conformers G and H, although in that case the difference in free energy is within the error of the computational method. Both structures G-2solv and H-2solv are similar, the lithium ion sitting between one oxygen of the pinacol, the carbamate, one methyl group on the migrating terminus (η 1 Li-H interaction) and the two solvent molecules. Scheme S2. Conformational analysis of the ate complex 4c. Gibbs free energies in solution (Et 2 O) computed at the LCCSD(T0)-F12/VDZ-F12//B3LYP-D2/6-31+G(d) level of theory (see text for details) and given with respect to the separated reactants MeBpin + MeCPhLiOCb.2Me 2 O. The same approach as described for 4b was used to generate conformers of 4c. Extra care had to be taken here with regard to the orientation of the phenyl group. This resulted in generation of two or three different input structures for some cases, but geometry optimization always converged to a unique conformer. Contrarily to what was expected, conformers A-2solv and G-2solv do not display any significant lithium-π interaction. Lithium interacts weakly with two carbons of the phenyl ring in A-2solv (Li Cphenyl = / Å) while it sits far from the aromatic in G-2solv (Li Cphenyl > 3.4 Å). On the other hand, lithium seems to interact more strongly with the phenyl ring in C-2solv (Li Cphenyl = up to Å). Lithium is slightly shifted from the top of the ring towards the migrating terminus to accommodate the much stronger lithium-carbamate interaction. The presence of a lithium-π interaction 5

6 in C-2solv certainly explains why this conformer is found less disfavoured in 4c (11.4 kcal mol 1 above G-2sol) than in 4a and 4b (respectively 18.1 and 24.3 kcal mol 1 above G-2sol). The conformers appear broadly in the same order as previously. G-2solv is the lowest in free energy, closely followed by H- 2solv. Sample Molpro Files LMP2 and LCCSD(T0) calculations memory,500,m gdirect symmetry,nosym,noorient geometry={ nb of atoms title geometry }! direct integral evaluations! recommended for local calculations basis=vdz hf basis={ default=avdz set,hf default=avdz/jkfit li=def2-atzvpp/jkfit set,df default=avdz/mp2fit set,cc default=avtz/mp2fit } df-hf,df_basis=hf locali,pipek;pipek,delete=2 df-lccsd(t0),basis_mp2=df,basis_ccsd=cc! accurate approximation of 4-external integrals in LCCSD! requires larger fitting basis sets than LMP2 LMP2-F12 calculations memory,500,m gdirect symmetry,nosym,noorient geometry={ nb of atoms! direct integral evaluations! recommended for local calculations 6

7 title geometry } basis=vdz hf basis={ default=vdz-f12 set,hf default=avdz/jkfit li=def2-atzvpp/jkfit set,df default=avdz/mp2fit set,jk default=vdz/jkfit li=def2-tzvpp/jkfit set,rib default=vdz-f12/optri } df-hf,df_basis=hf locali,pipek;pipek,delete=2 df-lmp2-f12,df_basis=df,df_basis_exch=jk,ri_basis=rib,ansatz=3*a(loc) 7

8 Energies and Frequencies E (Hartree) H (Hartree) G (Hartree) Low frequencies (cm -1 ) a a a TS 3a-4a a - A-1solv a - A-2solv a - A-3solv a - B-1solv a - B-2solv a - B-3solv a - C-2solv a - C-3solv a - D-2solv a - D-3solv a - E-2solv a - E-3solv a - G-1solv a - G-2solv a - H-1solv a - H-2solv a - I-1solv a - I-2solv TS 4a-5a - A-2solv TS 4a-5a - B-2solv a a Geometry optimization performed without dispersion. 8

9 E (Hartree) H (Hartree) G (Hartree) Low frequencies (cm -1 ) 2b b TS 3b-4b b - A-2solv b - B-2solv b - C-2solv b - G-2solv b - H-2solv b - I-2solv TS 4b-5b - B-2solv b E (Hartree) H (Hartree) G (Hartree) Low frequencies (cm -1 ) 2c c TS 3c-4c c - A-2solv c - B-2solv c - C-2solv c - G-2solv c - H-2solv c - I-2solv TS 4c-5c - A-2solv TS 4c-5c - B-2solv c

10 Cartesian coordinates B O C C C O C C C C H H H H H H H H H H H H H H H O N C C Li O C C O C C H H H H H H H H H H H H H H H H H H H H H H O C C H H H H H H C O C C C C H H H O C O N C H C H B

11 C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O C H H H C H H H C Li C H H H O C O N C H H H C H H H O C H H H C H H H O C B C C C O C C C H H H H H H H H H H H H H H H H Conformers of 4a. C B O C C C

12 O C N C C O C O C C C C Li O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C

13 H H H C H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H H O C H H H C H H H C C H H H O C O N C H C H B C

14 H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O C H H H C H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H H

15 C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H H O C H H H C H H H C B O C C C O C N C C O C O C C C C Li O C C

16 O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H

17 H O C H H H C H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O C H H H C H H H O C H H H C H H H C C H H H O C O N C H C H B C H H H H H

18 H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H H O C H H H C H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O C H

19 H H C H H H O C H H H C H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H H O C H H H C H H H C B O C C C O C N

20 C C O C O C C C C Li O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H

21 C H H H H H H H H H H H H C B O C C C O C N C C O C O C C C C Li O C C H H H H H H H H H H H H H H H H H H H H H H C C H H H O C O N C H C H B C H H H H H H H H O O C C C H H H C H H H C H H

22 H C H H H Li O O C H H H C H H H C H H H C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H C B O C C C O C N C C O C O C C C C Li O C C H H C C H H H O C O N C H C H B C H H H

23 H H H H H O O C C C H H H C H H H C H H H C H H H Li O O C H H H C H H H C H H H C H H H C C C O B O C C C H H H C O C O C N C C C Li O C C O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H

24 C B C O C C O C C C O C N C C C O C Li O C C O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H C C B O C C O C C C C C H H H H H H H H H H H H H H H H H H H O

25 C O H C C N C H O C H H H Li O C C H H H H H H H H H H H H H C C O C N C O C Li O C C O C C C H H H H H H H H H H H H H H H H H H H H H H H H Li O C N C O C C C C O C C O C C C B O C C C C H H H

26 H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H O C C B O C C C C C Li O C N C O C C C C O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H Conformers of 4b. C B O C C C O C N C C

Marek Pederzoli J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i.,

Supplementary Material: A New Approach to Molecular Dynamics with Non-adiabatic and Spin-orbit Effects with Applications to QM/MM Simulations of Thiophene and Selenophene Marek Pederzoli J. Heyrovský Institute