Supplementary Information for Magnesium-mediated Nucleophilic Borylation of Carbonyl Electrophiles Anne-Frédérique Pécharman, Michael S. Hill,* Claire L. McMullin* and Mary F. Mahon Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK -S1-
Figure S1: 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a reaction of 5 and 0.9 equivalents of benzophenone, illustrating the selectivity of the formation of compound 10 (Blue stars). Green stars 5; red stars 11. * * * * * * * * * * * * * * -S2-
Figure S2: 11 B{ 1 H} NMR (160 MHz, toluene-d 8 ) spectrum of an in situ reaction of 5 and 0.9 equivalents of benzophenone. Green star 5; red star 11. * * * -S3-
Figure S3: 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 10. -S4-
Figure S4: 13 C{ 1 H} NMR (126 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 10. -S5-
Figure S5: 11 B{ 1 H} NMR (160 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 10. -S6-
Figure S6: Stacked 1 H NMR (500 MHz, toluene-d 8 ) spectra of the reaction of compound 10 and 4- dimethylaminopyridine (DMAP) to form compound 7; green spectrum, compound 10; red spectrum, after adding 1 equivalent of DMAP; blue spectrum, crystallized sample of compound 7. -S7-
Figure S7: 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 11. -S8-
Figure S8: 13 C{ 1 H} NMR (126 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 11. -S9-
Figure S9: 11 B{ 1 H} NMR (160 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 11. -S10-
Figure S10: In situ 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a reaction of compound 5 and 1 equivalent of 9-fluorenone showing the formation of compound 12 and only 50% consumption of compound 10. -S11-
Figure S11: Resultant 11 B{ 1 H} NMR (160 MHz, toluene-d 8 ) spectrum of a reaction of compound 5 and 1 equivalent of 9-fluorenone. -S12-
Figure S12: 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 12. -S13-
Figure S13: 13 C{ 1 H} NMR (126 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 12. -S14-
Figure S14: 11 B{ 1 H} NMR (160 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 12. -S15-
Figure S15: 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 13. -S16-
Figure S16: 13 C{ 1 H} NMR (126 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 13. -S17-
Figure S17: 11 B{ 1 H} NMR (160 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 13. -S18-
Figure S18: 1 H NMR (500 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 14. -S19-
Figure S19: 13 C{ 1 H} NMR (126 MHz, toluene-d 8 ) spectrum of a crystallized sample of compound 14. -S20-
Figure S20: 11 B{ 1 H} NMR (160 MHz, v) spectrum of a crystallized sample of compound 14. -S21-
Single Crystal X-ray Diffraction analysis. Single Crystal X-ray diffraction data for compounds 10 14 were collected using CuKα (λ = 1.54184 Å) on a SuperNova, Dual Cu at zero, EosS2 diffractometer. The crystals were kept at 150(2) K during data collections. Using Olex2, 1 the structures were solved via SHELXS 2 and refined with the ShelXL refinement package using Least Squares minimisation. The asymmetric unit of compound 10 contains ½ of a molecule of hexane in addition to one molecule of the magnesium-containing complex. H48, attached to C48, was located and refined without restraints. In 13, the asymmetric unit contains one dimer molecule and two solvent regions. The first of the latter (based on C82) comprises one full molecule of toluene which is disordered in its entirety over 2 positions in a 60:40 ratio. The second guest (based on C89) is present at half occupancy and, as it also straddles a crystallographic inversion center, it is necessarily disordered with its symmetry related lattice equivalent. All solvent phenyl rings were treated as rigid hexagons, and ADP restraints were also included for the carbon atoms in the latter toluene moiety, to assist convergence. The pathway to the solution and refinement of compound 14 was impeded by a series of roadblocks. With a angle of close to 90 o, the data are credibly representative of orthorhombic symmetry. Indeed, the automated data reduction software suggested an R int of 0.0821 for a unit cell with mmm Laue symmetry wherein a, b, c,, and were, respectively, 26.5191(5), 20.7038(5), 17.0907(5) Å, 90, 90 and 90 o. A variety of orthorhombic space groups were interrogated and the best of these afforded only minimal success for a very restrained and disordered model. On re-examining the raw data, it became evident that the correct symmetry, as presented here, is monoclinic, with twinning of almost 180 o about the 0,0,1 direction. The data were integrated using this twin law but the angle coupled with the twin angle did not afford good quality, de-convoluted data (probably because of the high degree of reflection overlap). Hence, the data were integrated in the monoclinic setting, as for a single crystal, and the twin law applied, post integration, in the refinement. Thus, the asymmetric unit was found to comprise 2 crystallographically independent molecules which each exhibit disorder of all Bpin atoms with the exception of the boron centres. The disorder ratios were determined to be 75:25 and 60:40 for the moieties based on B1 and B2, respectively. B-O, O-C and C-C distances involving fractional occupancy atoms were restrained to being similar in the final least-squares refinement cycles. ADP restraints were also employed in the disordered regions, on merit, to assist convergence. -S22-
Table S1: Single Crystal X-ray Data Parameters for compounds 10 14. Compound 10 11 12 13 14 Empirical formula C 204 H 280 B 4 Mg 4 N 8 O 12 C 61 H 73 BMgN 2 O 4 C 61 H 69 BMgN 2 O 4 C 90.5 H 136 B 2 Mg 2 N 6 O 6 C 48 H 70 BMgN 3 O 3 Formula weight 3176.82 933.33 929.30 1474.28 772.19 Temperature/K 150.00(10) 150.00(10) 150.00(10) 150.00(10) 150.01(10) Crystal system monoclinic monoclinic monoclinic monoclinic monoclinic Space group P2 1 /c P2 1 /c P2 1 /n P2 1 /n P2 1 /n a/å 19.3609(4) 19.94583(19) 11.6688(6) 10.84470(10) 20.6974(5) b/å 12.1778(3) 12.68379(14) 40.0112(16) 21.5320(3) 17.0956(3) c/å 20.4699(5) 20.7639(2) 12.0303(6) 37.5348(8) 26.5234(5) / 90 90 90 90 90 β/ 104.869(3) 97.6957(10) 113.319(6) 93.567(2) 90.113(2) / 90 90 90 90 90 Volume/Å 3 4664.6(2) 5205.72(9) 5157.9(5) 8747.7(2) 9384.9(3) Z 1 4 4 4 8 ρ calc g/cm 3 1.131 1.191 1.197 1.119 1.093 μ/mm -1 0.647 0.672 0.678 0.658 0.635 F(000) 1724.0 2008.0 1992.0 3212.0 3360.0 Crystal size/mm 3 0.144 0.11 0.07 0.502 0.207 0.145 0.341 0.054 0.042 0.386 0.098 0.055 0.163 0.099 0.084 2Θ range for data collection/ 8.526 to 145.13 8.188 to 146.192 8.302 to 147.72 6.254 to 140.152 Reflections collected 65503 37599 39125 123143 66148 Independent reflections 9229 [R int = 0.0807, R sigma = 0.0432] 10341 [R int = 0.0277, R sigma = 0.0234] 10293 [R int = 0.0534, R sigma = 0.0520] 16619 [R int = 0.1101, R sigma = 0.0657] 6.666 to 146.54 18562 [R int = 0.0553, R sigma = 0.0593] Data/restraints/parameters 9229/0/546 10341/0/636 10293/0/636 16619/42/1055 18562/465/1180 Goodness-of-fit on F 2 1.037 1.012 1.021 1.186 1.038 Final R indexes [I>=2σ (I)] R 1 = 0.0485, wr 2 = 0.1107 R 1 = 0.0384, wr 2 = 0.1002 R 1 = 0.0510, wr 2 = 0.1173 R 1 = 0.0814, wr 2 = 0.1733 R 1 = 0.0680, wr 2 = 0.1777 Final R indexes [all data] R 1 = 0.0662, wr 2 = 0.1192 R 1 = 0.0445, wr 2 = 0.1048 R 1 = 0.0793, wr 2 = 0.1337 R 1 = 0.0974, wr 2 = 0.1798 R 1 = 0.0907, wr 2 = 0.1982 Largest diff. peak/hole / e Å -3 0.23/-0.22 0.29/-0.27 0.34/-0.25 0.34/-0.30 0.61/-0.66 -S23-
Computational Details / Methodology DFT calculations were run with Gaussian 09 (Revision D.01). 3 The Mg center was described with the Stuttgart RECPs and associated basis sets, 4 and 6-31G** basis sets were used for all other atoms (BS1). 5 Initial BP86 6 optimizations were performed using the grid = ultrafine option, with all stationary points being fully characterized via analytical frequency calculations as minima (all positive eigenvalues). All energies were recomputed with a larger basis set (BS2) featuring 6-311++G** on all atoms. Corrections for the effect of toluene (ε = 2.3741) solvent were run using the polarizable continuum model and BS1. 7 Single-point dispersion corrections to the BP86 results employed Grimme s D3 parameter set with Becke-Johnson damping as implemented in Gaussian. 8 References 1. Bourhis, L. J.; Dolomanov, O. V.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. Acta Cryst. A 2015, 71, 59-75. 2 Sheldrick, G. M. Acta Cryst. A, 2008, 64, 112-122. 3. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09 (Revision D.01); Gaussian Inc.: Wallingford, CT, 2009. 4. Andrae, D., Ha ußermann, U., Dolg, M., Stoll, H., Preuß, H., Theor. Chim. Acta 1990, 77, 123 141. 5. (a) Hariharan, P. C., Pople, J. A. Theor. Chim. Acta 1973, 28, 213 222. (b) Hehre, W. J., Ditchfield, R., Pople, J. A. J. Chem. Phys. 1972, 56, 2257. 6. (a) Becke, A. D. Phys. Rev. A: At., Mol., Opt. Phys. 1988, 38, 3098. (b) Perdew, J. P. Phys. Rev. B: Condens. Matter Mater. Phys. 1986, 33, 8822 8824. 7. Tomasi, J., Mennucci, B., Cammi, R. Chem. Rev. 2005, 105, 2999 3094. 8. S. Grimme, S. Ehrlich and L. Goerigk, Effect of the damping function in dispersion corrected density functional theory, J. Comp. Chem. 2011, 32, 1456-1465. -S24-
Breakdown of Energy Contributions The following tables detail the evolution of the relative energies as the successive corrections to the initial SCF energy are included. Terms used are: ΔE BS1 ΔH BS1 ΔG BS1 ΔG BS1/tol ΔG BS1/tol+D3 ΔG tol SCF energy computed with the BP86 functional with BS1 Enthalpy at 0 K with BS1 Free energy at 298.15 K and 1 atm with BS1 Free energy corrected for toluene solvent with BS1 Free energy corrected for toluene and dispersion effects with BS1 Free energy corrected for basis set (BS2), dispersion effects and toluene solvent In each case the final data used in the main article is highlighted in bold. Energy Tables Table S2 Computed relative energies (kcal/mol) for the reactions of complexes 7, 10, 11, 12, 13 and 11. Data in bold are those used in the main text. All energies are quoted relative to 9 at 0.0 kcal/mol. ΔE BS1 ΔH BS1 ΔG BS1 ΔG BS1/tol ΔG BS1/tol+D3 ΔE BS2 ΔG tol 5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 7-51.2-50.4-42.4 144.1-45.8-49.6-44.2 10-29.1-29.0-29.9 139.4-26.9-28.0-25.8 10ʹ -33.2-33.4-39.8 127.9-27.0-34.5-28.3 11-54.2-51.5-35.7 135.5-63.0-47.4-56.2 12-64.1-61.3-47.2 123.9-67.9-58.6-62.3 13-107.6-102.9-87.9 253.0-98.6-95.7-86.7 14-52.6-51.4-53.7 114.7-41.7-50.7-39.8 -S25-
Computed Energies (in Hartrees) n-bubpin SCF (BP86) Energy = -569.123611693 Enthalpy 0K = -568.827988 Enthalpy 298K = -568.811084 Free Energy 298K = -568.871244 Lowest Frequency = 17.1407 cm -1 Second Frequency = 53.5275 cm -1 SCF (Toluene) Energy = -569.125385795 SCF (BP86-D3BJ) Energy = -569.12538580 SCF (BS2) Energy = -569.267887458 benzophone SCF (BP86) Energy = -576.623309768 Enthalpy 0K = -576.437366 Enthalpy 298K = -576.425337 Free Energy 298K = -576.475232 Lowest Frequency = 42.1834 cm -1 Second Frequency = 64.3203 cm -1 SCF (Toluene) Energy = -576.626357410 SCF (BP86-D3BJ) Energy = -576.67027288 SCF (BS2) Energy = -576.769376102 fluorene SCF (BP86) Energy = -575.430864630 Enthalpy 0K = -575.266181 Enthalpy 298K = -575.255330 Free Energy 298K = -575.301574 Lowest Frequency = 94.8673 cm -1 Second Frequency = 126.1437 cm -1 SCF (Toluene) Energy = -575.434003837 SCF (BP86-D3BJ) Energy = -575.47710516 SCF (BS2) Energy = -575.574206025 -S26-
t-bunco SCF (BP86) Energy = -325.939448222 Enthalpy 0K = -325.807988 Enthalpy 298K = -325.798633 Free Energy 298K = -325.841059 Lowest Frequency = 30.1136 cm -1 Second Frequency = 110.1116 cm -1 SCF (Toluene) Energy = -325.941159610 SCF (BP86-D3BJ) Energy = -325.96011641 SCF (BS2) Energy = -326.031582028 Dipp-NCO SCF (BP86) Energy = -635.613561969 Enthalpy 0K = -635.348601 Enthalpy 298K = -635.331272 Free Energy 298K = -635.395037 Lowest Frequency = 5.4166 cm -1 Second Frequency = 22.3379 cm -1 SCF (Toluene) Energy = -635.615218208 SCF (BP86-D3BJ) Energy = -635.67182825 SCF (BS2) Energy = -635.774860796 5 SCF (BP86) Energy = -2220.57991976 Enthalpy 0K = -2219.487760 Enthalpy 298K = -2219.422702 Free Energy 298K = -2219.583100 Lowest Frequency = 18.9735 cm -1 Second Frequency = 26.5885 cm -1 SCF (Toluene) Energy = -2220.58694528 SCF (BP86-D3BJ) Energy = -2220.58694528 SCF (BS2) Energy = -2420.36376068 7 SCF (BP86) Energy = -2228.13252163 Enthalpy 0K = -2227.150396 Enthalpy 298K = -2227.088786 Free Energy 298K = -2227.250538 Lowest Frequency = 11.6887 cm -1 Second Frequency = 13.7455 cm -1 SCF (Toluene) Energy = -2228.14205949 SCF (BP86-D3BJ) Energy = -2610.77583892 SCF (BS2) Energy = -2427.92022190 10 SCF (BP86) Energy = -2228.12599633 Enthalpy 0K = -2227.143329 Enthalpy 298K = -2227.083501 Free Energy 298K = -2227.234693 Lowest Frequency = 12.0872 cm -1 Second Frequency = 23.6204 cm -1 SCF (Toluene) Energy = -2228.13301478 SCF (BP86-D3BJ) Energy = -2228.44325579 SCF (BS2) Energy = -2427.90980455 10ʹ SCF (BP86) Energy = -2610.41729276 Enthalpy 0K = -2609.276317 Enthalpy 298K = -2609.204317 Free Energy 298K = -2609.387629 Lowest Frequency = 10.0904 cm -1 Second Frequency = 19.5833 cm -1 SCF (Toluene) Energy = -2610.42623900 SCF (BP86-D3BJ) Energy = -2228.43151092 SCF (BS2) Energy = -2810.29764029 11 SCF (BP86) Energy = -2804.78932555 -S27-
Enthalpy 0K = -2803.616523 Enthalpy 298K = -2803.545252 Free Energy 298K = -2803.719261 Lowest Frequency = 19.8535 cm -1 Second Frequency = 25.6651 cm -1 SCF (Toluene) Energy = -2804.79633286 SCF (BP86-D3BJ) Energy = -2805.20472624 SCF (BS2) Energy = -3004.71017871 12 SCF (BP86) Energy = -2802.42023640 Enthalpy 0K = -2801.289786 Enthalpy 298K = -2801.220673 Free Energy 298K = -2801.390257 Lowest Frequency = 12.0864 cm -1 Second Frequency = 22.6344 cm -1 SCF (Toluene) Energy = -2802.42751046 SCF (BP86-D3BJ) Energy = -2802.82363812 SCF (BS2) Energy = -3002.33759032 13 SCF (BP86) Energy = -3954.96302299 Enthalpy 0K = -3953.099444 Enthalpy 298K = -3952.986356 Free Energy 298K = -3953.245919 Lowest Frequency = 12.4132 cm -1 Second Frequency = 15.3341 cm -1 SCF (Toluene) Energy = -3954.97066105 SCF (BP86-D3BJ) Energy = -3955.57518239 SCF (BS2) Energy = -4354.40739959 14 SCF (BP86) Energy = -2287.15368423 Enthalpy 0K = -2286.090205 Enthalpy 298K = -2286.024557 Free Energy 298K = -2286.192390 Lowest Frequency = 7.1562 cm -1 Second Frequency = 14.4176 cm -1 SCF (Toluene) Energy = -2287.16075906 SCF (BP86-D3BJ) Energy = -2287.46646098 SCF (BS2) Energy = -2486.95145993 -S28-