Deprotonative Cadmation of Functionalized Aromatics

Transcript

1 Deprotonative Cadmation of Functionalized Aromatics Jean-Martial L'Helgoual'ch, a Ghenia Bentabed-Ababsa, a,b Floris Chevallier, a Mitsuhiro Yonehara, c Masanobu Uchiyama,*,c Aïcha Derdour b and Florence Mongin*,a a Chimie et Photonique Moléculaires, UMR 6510 CNRS, Université de Rennes 1, Bâtiment 10A, Case 1003, Campus Scientifique de Beaulieu, Rennes, France. b Laboratoire Synthèse Organique Appliquée, Faculté des Sciences de l'université, BP 1524 Es-Sénia, Oran 31000, Algérie. c The Institute of Physical and Chemical Research, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama , Japan. florence.mongin@univ-rennes1.fr, uchi_yama@riken.jp Table of Contents Page S2 S2 S4 S8 S59 S60 Item General Methods Typical Procedures Compound Characterizations 1 H and 13 C NMR spectra Computational Methods Cartesian Coordinates and Total Electron Energies S1

2 General Methods All reactions were performed under argon atmosphere. THF was distilled over sodium/benzophenone. Nuclear magnetic resonance spectra were acquired on Bruker ARX-200 (200 MHz and 50 MHz for 1 H and 13 C respectively) and Bruker AC-300 (300 MHz and 75 MHz for 1 H and 13 C respectively) spectrometers. Chemical shifts are given in ppm as δ values relative to tetramethylsilane ( 1 H, 13 C) and coupling constants are given in Hz. High resolution mass spectra measurements and elemental analyses were performed at the CRMPO in Rennes (Centre Régional de Mesures Physiques de l Ouest) using respectively a Micromass MS/MS ZABSpec TOF instrument in EI mode and a Thermo-Finnigan Flash EA 1112 CHNS analyzer. Liquid chromatography separations were achieved on silica gel Merck Geduran Si 60 (40 63 mesh). Typical Procedures A. Deprotonative cadmation/iodination. To a stirred, cooled (0 C) solution of 2,2,6,6- tetramethylpiperidine (847 mg, 6.0 mmol) in THF (5 ml) were successively added n-buli (1.6 M hexanes solution, 6.0 mmol) and CdCl 2 TMEDA (599 mg, 2.0 mmol). The mixture was stirred for 10 min at 0 C before introduction of the aromatic substrate (4.0 mmol). After 2 h at room temperature, a solution of I 2 (1.52 g, 6.0 mmol) in THF (5 ml) was added. The mixture was stirred overnight before addition of an aqueous saturated solution of Na 2 S 2 O 3 (20 ml) and extraction with Et 2 O (20 ml) and CH 2 Cl 2 (3 20 ml). The combined organic layers were dried over MgSO 4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel gave the monoiodo derivative. B. Deprotonative dicadmation/diiodination. To a stirred, cooled (0 C) solution of 2,2,6,6- tetramethylpiperidine (1.69 g, 12.0 mmol) in THF (5 ml) were successively added n-buli (1.6 M S2

3 hexanes solution, 12.0 mmol) and CdCl 2 TMEDA (1.20 g, 4.0 mmol). The mixture was stirred for 10 min at 0 C before introduction of the aromatic substrate (4.0 mmol). After 2 h at room temperature, a solution of I 2 (3.05 g, 12.0 mmol) in THF (5 ml) was added. The mixture was stirred overnight before addition of an aqueous saturated solution of Na 2 S 2 O 3 (20 ml) and extraction with Et 2 O (20 ml) and CH 2 Cl 2 (3 20 ml). The combined organic layers were dried over MgSO 4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel gave the diiodo derivative. C. Deprotonative cadmation/benzoylation. To a stirred, cooled (0 C) solution of 2,2,6,6- tetramethylpiperidine (847 mg, 6.0 mmol) in THF (5 ml) were successively added n-buli (1.6 M hexanes solution, 6.0 mmol) and CdCl 2 TMEDA (599 mg, 2.0 mmol). The mixture was stirred for 10 min at 0 C before introduction of furan (272 mg, 4.0 mmol). After 2 h at room temperature, a solution of benzoyl chloride (843 mg, 6.0 mmol) in THF (5 ml) was added at 0 C. The mixture was stirred overnight before addition of an aqueous saturated solution of NaHCO 3 (20 ml) and extraction with Et 2 O (20 ml) and CH 2 Cl 2 (3 20 ml). The combined organic layers were dried over MgSO 4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel gave the benzoyl derivative. D. Deprotonative cadmation/cross coupling. To a stirred, cooled (0 C) solution of 2,2,6,6- tetramethylpiperidine (847 mg, 6.0 mmol) in THF (5 ml) were successively added n-buli (1.6 M hexanes solution, 6.0 mmol) and CdCl 2 TMEDA (599 mg, 2.0 mmol). The mixture was stirred for 10 min at 0 C before introduction of furan (272 mg, 4.0 mmol). After 2 h at room temperature, the Pd(OAc) 2 (54 mg, 6 mol %), dppf (133 mg, 6 mol %) and 4-bromoanisole (748 mg, 4.0 mmol) were successively added. The solution was heated at reflux for 18 h before addition of water (1 ml) and AcOEt (20 ml). The reaction mixture was filtered on celite, dried over MgSO 4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel gave the cross-coupling product. S3

4 Compound Characterizations OMe I 2-Iodoanisole (2a), 1 prepared using the general procedure A, 74% yield, orange oil. 1 H NMR (CDCl 3, 200 MHz): δ 3.80 (s, 3H), 6.70 (dt, 1H, J = 1.3 and 7.6), 6.79 (dd, 1H, J = 1.3 and 8.3), 7.28 (ddd, 1H, J = 1.6, 7.4 and 8.3), 7.77 (dd, 1H, J = 1.6 and 7.6). 13 C NMR (CDCl 3, 50 MHz): δ 56.0, 85.8, 110.7, 122.2, 129.3, 139.1, MeO 1-Iodo-2,3-dimethoxybenzene (2b), 2 prepared using the general procedure A, 79% yield, orange oil. 1 H NMR (CDCl 3, 200 MHz): δ 3.83 (s, 3H), 3.85 (s, 3H), 6.83 (m, 2H), 7.34 (dd, 1H, J = 1.8 and 7.6). 13 C NMR (CDCl 3, 50 MHz): δ 56.1, 60.5, 92.7, 112.9, 126.1, 130.7, 149.1, O NEt 2 OMe N,N-Diethyl-2-iodobenzamide (2c), 3 prepared using the general procedure A, 91% yield, yellow oil. 1 H NMR (CDCl 3, 200 MHz): δ 1.04 (t, 3H, J = 7.1), 1.27 (t, 3H, J = 7.1), 3.10 (m, 2H), 3.30 (m, 1H), 3.80 (m, 1H), 7.04 (dt, 1H, J = 1.8 and 7.5), 7.18 (dd, 1H, J = 1.8 and 7.5), 7.36 (dt, 1H, J = 1.0 and 7.5), 7.78 (dd, 1H, J = 1.0 and 7.5). 13 C NMR (CDCl 3, 50 MHz): δ 12.0, 13.4, 38.4, 42.3, 92.3, 126.3, 127.7, 129.4, 138.5, 142.2, I CO 2 Me I Methyl 2-iodobenzoate (2d), 4 prepared using the general procedure A, 62% yield, yellow oil. 1 H NMR (CDCl 3, 200 MHz): δ 3.94 (s, 3H), 7.15 (dt, 1H, J = 1.8 and 7.6), 7.40 (dt, 1H, J = 1.2 and 7.6), 7.81 (dd, 1H, J = 1.8 and 7.6), 7.99 (dd, 1H, J = 1.8 and 7.6). 13 C NMR (CDCl 3, 50 MHz): δ 52.2, 93.9, 127.7, 130.7, 132.4, 134.7, 141.0, CN I I 2-Iodobenzonitrile (2e), 1 prepared using the general procedure A, 68% yield, orange solid (mp C). 1 H NMR (CDCl 3, 200 MHz): δ 7.28 (dt, 1H, J = 1.7 and 7.6), 7.45 (dt, 1H, J = 1.1 and 7.6), 7.60 (dd, 1H, J = 1.7 and 7.6), 7.91 (dd, 1H, J = 1.1 and 7.6). 13 C NMR (CDCl 3, 50 MHz): δ 98.4, 119.4, 120.6, 128.4, 133.8, 134.3, O I 2-Iodobenzophenone (2f), 5 prepared using the general procedure A, 66% yield, yellow oil. 1 H NMR (CDCl 3, 200 MHz): δ 7.18 (dt, 1H, J = 1.8 and 7.4), 1 Uchiyama, M.; Naka, H., Matsumoto, Y.; Ohwada, T. J. Am. Chem. Soc. 2004, 126, Naka, H.; Uchiyama, M.; Matsumoto, Y.; Wheatley, A. E. H.; McPartlin, M.; Morey, J. V.; Kondo, Y. J. Am. Chem. Soc. 2007, 129, Sapountzis, I., PhD Thesis, University of Munich, Dahl, B. J.; Branchaud, B. P. Tetrahedron Lett. 2004, 45, Trybulski, E. J.; Reeder, E.; Blount, J. F.; Walser, A.; Fryer, R. I. J. Org. Chem. 1982, 47, S4

5 7.30 (dd, 1H, J = 1.8 and 7.6), 7.47 (m, 3H), 7.62 (m, 1H), 7.81 (m, 2H), 7.93 (dd, 1H, J = 0.9 and 7.9). 13 C NMR (CDCl 3, 50 MHz): δ 92.3, 127.9, 128.6, (2C), (2C), 131.3, 133.9, 135.7, 139.8, 144.4, O Br O I I I 4-Bromo-2-iodoanisole (2g), 6 prepared using the general procedure A, 97% yield, yellow solid (mp C). 1 H NMR (CD 3 COCD 3, 200 MHz): δ 3.87 (s, 3H), 6.90 (d, 1H, J = 8.8), 7.47 (dd, 1H, J = 2.4 and 8.8), 7.88 (d, 1H, J = 2.4). 13 C NMR (CD 3 COCD 3, 50 MHz): δ 56.9, 87.1, 113.3, 113.4, 133.0, 141.4, ,4-Diiodoanisole (2h), 7 prepared using the general procedure A, 83% yield, red solid (mp < 50 C). 1 H NMR (CDCl 3, 200 MHz): δ 3.80 (s, 3H), 6.51 (d, 1H, J = 8.6), 7.51 (dd, 1H, J = 2.1 and 8.6), 8.00 (d, 1H, J = 2.1). 13 C NMR (CDCl 3, 50 MHz): δ 56.4, 83.4, 87.5, 112.6, 138.0, 146.2, CO 2 Me I Methyl 4-bromo-2-iodobenzoate (2i), prepared using the general procedure A, 60% yield, orange solid (mp < 50 C). 1 H NMR (CDCl 3, 200 MHz): δ 3.89 (s, 3H), 7.49 (dd, 1H, J = 1.9 and 8.4), 7.65 (d, 1H, J = 8.4), 8.12 (d, 1H, J = 1.9). 13 C NMR (CDCl 3, 50 Br MHz): δ 52.7, 95.0, 126.7, 131.2, 132.0, 133.4, 143.5, HRMS: calcd for C 8 H 6 BrIO 2 : , found: Iodobenzo[b]thiophene (2j), 8 prepared using the general procedure A, 97% I yield, yellow solid (mp 64 C). 1 H NMR (CDCl 3, 200 MHz): δ (m, 2H), S 7.48 (s, 1H), (m, 2H). 13 C NMR (CDCl 3, 50 MHz): δ 79.3, 121.3, 122.4, 124.5, 124.6, 133.9, 140.9, Iodobenzo[b]furan (2k), 9 prepared using the general procedure A, 84% yield, I yellow oil. 1 H NMR (CDCl 3, 200 MHz): δ 6.98 (s, 1H), (m, 2H), O 7.57 (m, 2H). 13 C NMR (CDCl 3, 50 MHz): δ 96.0, 111.0, 117.4, 119.8, 123.3, 124.4, 129.3, N Boc I N-Boc-2-iodopyrrole (2l), 10 prepared using the general procedure A, 68% yield, pale yellow oil. 1 H NMR (CDCl 3, 200 MHz): δ 1.62 (s, 9H), 6.17 (t, 1H, J = 3.4), 6.53 (dd, 1H, J = 3.4 and 1.8), 7.39 (dd, 1H, J = 3.6 and 2.0). 13 C NMR (CDCl 3, 50 MHz): δ 27.9 (3C), 63.1, 84.6, 113.5, 124.8, 125.4, Muraki, T.; Togo, H.; Yokoyama, M. J. Org. Chem. 1999, 64, Hubig, S. M.; Jung, W.; Kochi, J. K. J. Org. Chem. 1994, 59, Vallgårda, J.; Appelberg, U.; Arvidsson, L.-E.; Hjorth, S.; Svensson, B. E.; Hacksell, U. J. Med. Chem. 1996, 39, Mongin, F.; Bucher, A.; Bazureau, J. P.; Bayh, O.; Awad, H.; Trécourt, F. Tetrahedron Lett. 2005, 46, Chen, W.; Cava, M. P. Tetrahedron Lett. 1987, 28, S5

6 N I 2-Iodobenzothiazole (2m), 11 prepared using the general procedure A, 97% S yield, yellow solid (mp 80 C). 1 H NMR (CDCl 3, 200 MHz): δ (m, 2H), (m, 1H), (m, 1H). 13 C NMR (CDCl 3, 50 MHz): δ 105.8, 120.6, 122.7, 125.8, 126.5, 139.3, N 2-Iodobenzoxazole (2n), 12 prepared using the general procedure A, 63% yield, I yellow solid (mp 90 C). 1 H NMR (CDCl 3, 200 MHz): δ (m, 2H), O 7.50 (m, 1H), (m, 1H). 13 C NMR (CDCl 3, 50 MHz): δ 109.2, 109.9, 118.9, 124.4, 125.1, 142.3, N N I 3-Iodopyridazine (2o), 13 prepared using the general procedure A, 55% yield, pale brown solid (mp 139 C). 1 H NMR (CDCl 3, 200 MHz): δ 7.17 (dd, 1H, J = 4.8 and 8.6), 7.89 (dd, 1H, J = 1.5 and 8.6), 9.15 (dd, 1H, J = 1.5 and 4.8). 13 C NMR (CDCl 3, 50 MHz): δ 125.8, 127.3, 137.3, Iodopyridazine (2'o), 13 prepared using the general procedure A, 41% yield, pale N N brown solid (mp 117 C). 1 H NMR (CDCl 3, 200 MHz): δ 7.89 (dd, 1H, J = 2.1 and 5.3), I 8.82 (d, 1H, J = 5.3), 9.44 (br s, 1H). 13 C NMR (CDCl 3, 50 MHz): δ 101.0, 135.5, 151.1, Iodopyrimidine (2p), 13 prepared using the general procedure A, 71% yield, yellow N I solid (mp 112 C). 1 H NMR (CDCl 3, 200 MHz): δ 7.79 (dd, 1H, J = 1.3 and 5.3), 8.25 N (d, 1H, J = 5.3), 8.89 (d, 1H, J = 1.3). 13 C NMR (CDCl 3, 50 MHz): δ 129.6, 133.2, 156.2, N N I Iodopyrazine (2q), 13 prepared using the general procedure A, 59% yield, yellow solid (mp 90 C). 1 H NMR (CDCl 3, 200 MHz): δ 8.38 (dd, 1H, J = 1.3 and 2.8), 8.50 (d, 1H, J = 2.8), 8.86 (d, 1H, J = 1.3). 13 C NMR (CDCl 3, 50 MHz): δ 118.5, 142.9, 145.8, I N N 2,5-Diiodopyrazine (3q), prepared using the general procedure B, 58% yield, yellow solid (mp 141 C). 1 H NMR (CDCl 3, 200 MHz): δ 8.63 (s, 2H). 13 C NMR (CDCl 3, 50 MHz): δ (2C), (2C). HRMS: calcd for C 4 H 2 I 2 N 2 : , found: Anal. Calcd for C 4 H 2 I 2 N 2 : C, 14.48; H, 0.61; N, Found: C, 14.31; H, 0.69; N, I 11 Van den Hoven, B. G.; Alper, H. J. Am. Chem. Soc. 2001, 123, Bayh, O.; Awad, H.; Mongin, F.; Hoarau, C.; Bischoff, L.; Trécourt, F.; Quéguiner, G.; Marsais, F.; Blanco, F.; Abarca, B.; Ballesteros, R. J. Org. Chem. 2005, 70, Seggio, A.; Chevallier, F.; Vaultier, M.; Mongin, F. J. Org. Chem. 2007, 72, S6

7 N 2,5-Diiodothiazole (3r), 14 prepared using the general procedure B, 50% yield, I S I yellow solid (mp 110 C). 1 H NMR (CDCl 3, 300 MHz): δ 7.62 (s, 1H). 13 C NMR (CDCl 3, 75.5 MHz): δ 74.8, 104.1, I S I 2,5-Diiodothiophene (3s), 15 prepared using the general procedure B, 74% yield, yellow solid (mp < 50 C). 1 H NMR (CDCl 3, 300 MHz): δ 6.94 (s, 2H). 13 C NMR (CDCl 3, 75.5 MHz): δ 76.3 (2C), (2C). O O 2,5-Diiodo-3,4-ethylenedioxythiophene (3t), 16 prepared using the general procedure B, 81% yield, yellow solid (mp 183 C). 1 H NMR (CDCl 3, 300 MHz): δ I S I 4.26 (s, 4H). 13 C NMR (CDCl 3, 75.5 MHz): δ 51.9 (2C), 65.3 (2C), (2C). I N-Boc-2,5-diiodopyrrole (3l), prepared using the general procedure B, 60% yield, yellow oil. 1 H NMR (CDCl 3, 300 MHz): δ 1.67 (s, 9H), 6.46 (s, 2H). 13 C NMR (CDCl 3, 75.5 MHz): δ 28.1 (3C), 64.8, 86.8 (2C), (2C), HRMS: calcd for C 9 H 11 I 2 NO 2 : , found: Furan-2-yl-phenylmethanone (4u), 17 prepared using the general procedure C, O O 76% yield, yellow oil. 1 H NMR (CDCl 3, 300 MHz): δ 6.59 (dd, 1H, J = 1.7 and 3.6), 7.23 (dd, 1H, J = 0.7 and 3.6), (m, 3H), 7.7 (dd, 1H, J = 0.7 and 1.7), 7.97 (m, 2H). 13 C NMR (CDCl 3, 75.5 MHz): δ 112.3, 120.7, (2C), (2C), 132.7, 137.4, 147.2, 152.4, O N Boc I O 2-(4-Methoxyphenyl)furan (5u), 18 prepared using the general procedure D, 86% yield, yellow solid (mp C). 1 H NMR (CDCl 3, 300 MHz): δ 3.84 (s, 3H), 6.47 (dd, 1H, J = 1.8 and 3.5), 6.54 (d, 1H, J = 3.5), 6.95 (d, 2H, J = 8.9), 7.46 (d, 1H, J = 1.8), 7.64 (d, 2H, J = 8.9). 13 C NMR (CDCl 3, 75.5 MHz): δ 55.3, 103.5, 111.6, (2C), 124.1, (2C), 141.5, 154.1, Dondoni, A.; Mastellari, A. R.; Medici, A.; Negrini, E.; Pedrini, P. Synthesis 1986, Schanze, K. S.; Silverman, E. E.; Zhao, X. J. Phys. Chem. B 2005, 109, Meng, H.; Perepichka, D. F.; Bendikov, M.; Wudl, F.; Pan, G. Z.; Yu, W.; Dong, W.; Brown, B. J. Am. Chem. Soc. 2003, 125, Crawford, J. J.; Henderson, K. W.; Kerr, W. J. Org. Lett. 2006, 8, Tanis, S. T.; Deaton, M. V.; Dixon, L. A.; Mcwilliams, M. C.; Raggon, J. W., Collins, M. A. J. Org. Chem. 1998, 63, S7

8 1 H and 13 C NMR spectra 2-Iodoanisole (2a). S8

9 2-Iodoanisole (2a). S9

10 1-Iodo-2,3-dimethoxybenzene (2b). S10

11 1-Iodo-2,3-dimethoxybenzene (2b). S11

12 N,N-Diethyl-2-iodobenzamide (2c). S12

13 N,N-Diethyl-2-iodobenzamide (2c). S13

14 Methyl 2-iodobenzoate (2d). S14

15 Methyl 2-iodobenzoate (2d). S15

16 2-Iodobenzonitrile (2e). S16

17 2-Iodobenzonitrile (2e). S17

18 2-Iodobenzophenone (2f). S18

19 2-Iodobenzophenone (2f). S19

20 4-Bromo-2-iodoanisole (2g). S20

21 4-Bromo-2-iodoanisole (2g). S21

22 2,4-Diiodoanisole (2h). S22

23 2,4-Diiodoanisole (2h). S23

24 Methyl 4-bromo-2-iodobenzoate (2i). S24

25 Methyl 4-bromo-2-iodobenzoate (2i). S25

26 2-Iodobenzo[b]thiophene (2j). S26

27 2-Iodobenzo[b]thiophene (2j). S27

28 2-Iodobenzo[b]furan (2k). S28

29 2-Iodobenzo[b]furan (2k). S29

30 N-Boc-2-iodopyrrole (2l). S30

31 N-Boc-2-iodopyrrole (2l). S31

32 2-Iodobenzothiazole (2m). S32

33 2-Iodobenzothiazole (2m). S33

34 2-Iodobenzoxazole (2n). S34

35 2-Iodobenzoxazole (2n). S35

36 3-Iodopyridazine (2o). S36

37 3-Iodopyridazine (2o). S37

38 4-Iodopyridazine (2'o). S38

39 4-Iodopyridazine (2'o). S39

40 4-Iodopyrimidine (2p). S40

41 4-Iodopyrimidine (2p). S41

42 2-Iodopyrazine (2q). S42

43 2-Iodopyrazine (2q). S43

44 2,5-Diiodopyrazine (3q). S44

45 2,5-Diiodopyrazine (3q). S45

46 2,5-Diiodothiazole (3r). S46

47 2,5-Diiodothiazole (3r). S47

48 2,5-Diiodothiophene (3s). S48

49 2,5-Diiodothiophene (3s). S49

50 2,5-Diiodo-3,4-ethylenedioxythiophene (3t). S50

51 2,5-Diiodo-3,4-ethylenedioxythiophene (3t). S51

52 N-Boc-2,5-diiodopyrrole (3l). S52

53 N-Boc-2,5-diiodopyrrole (3l). S53

54 2-(Benzoyl)furan (4u). S54

55 2-(Benzoyl)furan (4u). S55

56 2-(4-Methoxyphenyl)furan (5u). S56

57 2-(4-Methoxyphenyl)furan (5u). S57

58 Comparison between the NMR spectra of the basic mixtures S58

59 Computational Methods All calculations were carried out with the Gaussian 03 program package. 19 The molecular structures and harmonic vibrational frequencies were obtained at the B3LYP 20 level with the basis set of Ahlrichs' SVP all electron basis set for Zn 21 and Cd, 22 and 6 31G* for the other atoms. Geometry optimization and vibrational analysis were performed at the same level. All stationary points were optimized without any symmetry assumptions, and characterized by normal coordinate analysis at the same level of theory (the number of imaginary frequencies, NIMAG, was 0 for minima). 19 Gaussian 03, revision B.04; Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.; Gaussian, Inc.: Pittsburgh, PA, (a) Becke, A. D. Phys. Rev. 1988, A38, (b) Becke, A. D. J. Chem. Phys. 1993, 98, (c) Becke, A. D. J. Chem. Phys. 1993, 98, (d) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. 1988, B37, Schäfer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, Ahlrichs, R.; May, K. Phys. Chem. Chem. Phys. 2000, 2, S59

60 Cartesian Coordinates and Total Electron Energies Scheme 1. LiTMP 2.15 ΔG = +3.8 kcal/mol (TMP) 2 Zn N Zn N 1.95 Li N = TMP 96.9 N LiTMP 2.38 ΔG = -5.6 kcal/mol (TMP) 2 Cd N Cd N 1.96 Li 90.7 N LiTMP HF= Sum of electronic and thermal Free Energies= Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S60

61 (TMP) 2 Zn HF= Sum of electronic and thermal Free Energies= Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S61

62 S62

63 (TMP) 3 ZnLi HF= Sum of electronic and thermal Free Energies= Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S63

64 S64

65 S65

66 (TMP) 2 Cd HF= Sum of electronic and thermal Free Energies= Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S66

67 S67

68 (TMP) 3 CdLi HF= Sum of electronic and thermal Free Energies= Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S68

69 S69

70 S70