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1 Supporting Information for: E pluribus unum: Isolation, structure determination, network analysis and DFT studies of a single metastable structure from a shapeshifting mixture of 852 bullvalene structural isomers Maggie He and Jeffrey W. Bode* Laboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences ETH Zürich, Wolfgang Pauli Strasse 10, 8093 Zürich, Switzerland bode@org.chem.ethz.ch Contents I. General Procedures S2 II. III. IV. Isolation and Characterization of fraction e...s2 Evidence that fraction e was not induced by HPLC column s15 Code generation...s15 V. Cope rearrangements...s17 VI. VII. Interconversion network.. S19 Experimental half-life of fraction e. S20 VIII. Simulated half-life of fraction e.. S21 IX. Simulated half-life of fraction e analogue without the ester...s23 X. Computation details.....s25 XI. XII. XIII. Free energy comparison between B3LYP/6-31G(d) and M06-2X/6-31+G(d,p)....S26 Full reference for Gaussian S27 Cartesian coordinates of calculated structures....s28 Page S1 of 138

2 I. General Procedures 1 H, 13 C and 2D-NMR spectra were measured on Bruker 500 or 600 MHz spectrometer. Chemical shifts are expressed in parts per million (ppm) downfield from residual solvent peaks and coupling constants are reported as Hertz (Hz). NMR splitting parameter are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublet; m, multiplet. II. Isolation and Characterization of Fraction e Bullvalene 6 (~ 4 mg) was injected onto an achiral preparative HPLC (Alltima Silica column, mm ID, EtOAc:Hex 1:9, 10 ml/min flow rate, 286 nm detection) at rt, fraction e (Figure S1) was collected and kept at 20 C. Another fraction containing other bullvalene mixture was also collected. This fraction of bullvalene isomers was heated in a water bath at 55 C for 30 min, concentrated down under reduced pressure and resubjected to preparative HPLC separation. After eight successive HPLC separations, the combined fraction e was concentrated under reduced pressure and dried under vacuum at 0 C. Approximately 1 mg of fraction e was obtained. Fraction e was dissolved in 150 μl of CD 2 Cl 2 and transferred to a 3 mm outer diameter Shigemi NMR microtube that has magnetic susceptibility matched to CDCl 3 for NMR analysis (500 MHz, 1 H, 13 C, COSY, HSQC and HMBC) at 20 C. 1 H NMR (500 MHz, CD 2 Cl 2, 20 C) δ 7.43 (d, 2H, J = 7.8 Hz), 7.29 (t, 2H, J = 7.5 Hz), (m, 1H), 7.21 (t, 1H, 7.5 Hz), (m, 1H), (m, 1H), 4.93 (d, 1H, J = 17.1 Hz), 4.78 (d, 1H, J = 10.0 Hz), (m, 2H), 4.08 (s, 1H), 3.91 (dd, 2H, J = 1.8 Hz, J = 6.7 Hz), (m, 2H), (m, 2H), 2.51 (q, 1H, J = 8.5 Hz), (m, 1H), 1.28 (t, 3H, J = 7.2 Hz), 0.92 (d, 6H, J = 6.7 Hz). 13 C NMR (500 MHz, CD 2 Cl 2, 20 C) δ165.6, 153.8, 142.5, 139.5, 138.9, 138.4, 134.4, 128.7, 128.5, 127.1, 126.2, 124.5, 123.9, 116.5, 74.8, 61.3, 36.4, 36.3, 28.0, 26.4, 22.0, 20.4, 18.9, Figure S1. Preparative HPLC trace of bullvalene 6. Page S2 of 138

3 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) Page S3 of 138

4 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) Page S4 of 138

5 H 3 C 23 CH O 2 O O O O H 3 C Page S5 of 138 (500 MHz, CD 2 Cl 2, 20 C) DQF-COSY

6 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HSQC Page S6 of 138

7 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HSQC Expansion 1 Page S7 of 138

8 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HSQC Expansion 2 Page S8 of 138

9 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HMBC Page S9 of 138

10 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HMBC Expansion 1 Page S10 of 138

11 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HMBC Expansion 2 Page S11 of 138

12 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HMBC Expansion 3 Page S12 of 138

13 O H 3 C O 23 O CH O H 3 C O (500 MHz, CD 2 Cl 2, 20 C) HMBC Expansion 4 Page S13 of 138

14 1 H NMR (600 MHz, CD 2Cl2) of fraction e taken at different times upon standing at rt after it is removed from 20 C. Page S14 of 138

15 III. Evidence that fraction e was not induced by HPLC column To ensure that the isomerization of fraction e is not induced by the HPLC column, the fraction shaded in gray below (Figure S2) was isolated (Alltima Silica column, mm ID, EtOAc:Hex 1:9, 1 ml/min flow rate, 254 nm detection) concentrated at 0 C under reduced pressure, and reinjected onto the HPLC. No fraction e was observed upon reinjection. This supported the conjecture that fraction e was not formed because of HPLC column Retention time (min) Retention time (min) Figure S2. Isolation of bullvalene fraction and its reinjection HPLC trace. IV. Code generation Each isomer of bullvalene 6 can be represented by a 10-digit number. This 10-digit number codes the substitutions as well as their positions on the bulvalene core. Numbers 1, 2, 3, and 4 represents the substituents isobutyl carbonate, phenyl, ethyl ester and allyl respectively. Zero means no substitution, or just hydrogen, on the carbon. The position of the carbons of the bullvalene core is represented in the code in the order from left to right, coding arm 1, arm 2, arm 3 and methine carbon (Figure S3). Page S15 of 138

16 arm 1 arm 2 arm 3 methine C Figure S3. Position of bullvalene core carbons in the code. To generate the complete interconvertion network of bullvalene 6. The codes for all 1680 isomers were created using the computer program Matlab (R2010b). Matlab command: a=perms([ ]) b=unique(a, 'rows') arm1=b(:, 1:3) arm2=b(:, 4:6) arm3=b(:, 7:9) methinec=b(:, 10) c=cat(2, arm2, arm3, arm1, methinec) d=cat(2, arm3, arm1, arm2, methinec) dlmwrite('startcode1', b, '') dlmwrite('startcode2', c, '') dlmwrite('startcode3', d, '') Import the text file startcode1, startcode2, startcode3 back to Matlab. This was done by clicking [File], [Import Data ], select the file startcode1, [Open], select Other for column separator and leave it blank, [Next], [Finish]. e=cat(2, startcode1, startcode2, startcode3) f=sort(e, 2) g=f(:, 1) smalleststartcode=unique(g) h=sprintf('%010d\n', smalleststartcode) dlmwrite('j', h, ' ') Page S16 of 138

17 The perms command generates all of the possible permutations of the 10 numbers. This gives 3,628,800 permutations. Most of these permutations repeats and therefore the unique(a, rows ) command was used to remove the arrays that repeats. The unique command gives 5040 nonrepetitive permutations. Since each bullvalene isomer can be represented by three codes (see main text Figure 3) we selected the 10-digit number with the smallest value to represent each isomer. The text file j contains the numeric codes for all 1680 isomers of bullvalene 6. V. Cope rearrangements Continued from Section IV Code generation, the following commands and steps were carried out in Matlab. Import the text file j by clicking [File], [Import Data ], select the file j, [Open], select Space for column separator, [Next], [Finish]. c1=j(:,1) c2=j(:,2) c3=j(:,3) c4=j(:,4) c5=j(:,5) c6=j(:,6) c7=j(:,7) c8=j(:,8) c9=j(:,9) c10=j(:,10) ra1code1=cat(2, c10, c9, c8, c6, c5, c4, c3, c2, c1, c7) ra1code2=cat(2, c6, c5, c4, c3, c2, c1, c10, c9, c8, c7) ra1code3=cat(2, c3, c2, c1, c10, c9, c8, c6, c5, c4, c7) ra2code1=cat(2, c9, c8, c7, c6, c5, c4, c10, c3, c2, c1) ra2code2=cat(2, c6, c5, c4, c10, c3, c2, c9, c8, c7, c1) ra2code3=cat(2, c10, c3, c2, c9, c8, c7, c6, c5, c4, c1) ra3code1=cat(2, c9, c8, c7, c10, c6, c5, c3, c2, c1, c4) ra3code2=cat(2, c10, c6, c5, c3, c2, c1, c9, c8, c7, c4) ra3code3=cat(2, c3, c2, c1, c9, c8, c7, c10, c6, c5, c4) Page S17 of 138

18 dlmwrite('ra1code1t', ra1code1, '') dlmwrite('ra1code2t', ra1code2, '') dlmwrite('ra1code3t', ra1code3, '') dlmwrite('ra2code1t', ra2code1, '') dlmwrite('ra2code2t', ra2code2, '') dlmwrite('ra2code3t', ra2code3, '') dlmwrite('ra3code1t', ra3code1, '') dlmwrite('ra3code2t', ra3code2, '') dlmwrite('ra3code3t', ra3code3, '') Import the text file ra1code1t, ra1code2t, ra1code3t, ra2code1t, ra2code2t, ra2code3t, ra3code1t, ra3code2t and ra3code3t into Matlab separately by clicking [File], [Import Data ], select the file, [Open], select Other for column separator and leave it blank, [Next], [Finish]. k1=cat(2, ra1code1t, ra1code2t, ra1code3t) k2=cat(2, ra2code1t, ra2code2t, ra2code3t) k3=cat(2, ra3code1t, ra3code2t, ra3code3t) L1=sort(k1, 2) L2=sort(k2, 2) L3=sort(k3, 2) m1=l1(:, 1) m2=l2(:, 1) m3=l3(:, 1) n=cat(1, m1, m2, m3) p=cat(1, smalleststartcode, smalleststartcode, smalleststartcode) n10d=sprintf('%010d\n', n) p10d=sprintf('%010d\n', p) dlmwrite('nodea', n10d, '') dlmwrite('nodeb', p10d, '') Open Microsoft Excel for Mac 2011 (version ). Click on cell A1, go to [File], [Import ], select Text file, then [Import]. Go to the folder where NodeA is saved, enable Text Files, select the file NodeA and click [Get Data]. When the Text Import Wizard come up, leave Delimited under Original data type selected, click [Next], [Next] again, select Text under Column data format and Page S18 of 138

19 click [Finish]. In the Import Data window, select Existing sheet = $A$1 and click [OK]. Click on cell B1 and import the file NodeB using the same steps. Select cells A1:B5040, go to [File], [Save As ], save as Network data in the format of Tab Delimited Text (.txt). The Network data text file contains all the possible rearrangements of bullvalene 6. Each line in this file represents one rearrangement between two isomers. VI. Interconversion network To visualize the interconversion network of bullvalene, the program NAViGaTOR2.2.1 (< was used. Open NAViGaTOR. Click [Browse ]. Select (.txt) Tab-delimited Data for the File Format. Select the text file Network data and click [Open]. Set Header Size (rows) = 0 and Title Row = 0, then click [Next]. Select Node A ID under NodeA and select Node B ID under NodeB. Click [Next], then click [Done]. Further organization and formatting with NAViGaTOR generated the network map shown in Figure S4 with fraction e in the center and each ring of dots represents a successive generations of rearrangements. Page S19 of 138

$Experimental half-life of fraction e Fraction e was isolated by preparative HPLC (Alltima Silica column, 250 22 mm ID, EtOAc:Hex 1:9, 10 ml/min flow rate, 286 nm detection) at rt (23 C).$

20 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry Figure S4. Interconversion network of bullvalene 6. VII. Experimental half-life of fraction e Fraction e was isolated by preparative HPLC (Alltima Silica column, mm ID, EtOAc:Hex 1:9, 10 ml/min flow rate, 286 nm detection) at rt (23 C). The solvent was removed under reduced pressure at rt and a solution of naphthalene in EtOAc:Hex 1:9 was added. This sample was injected onto an analytical HPLC (Alltima Silica column, mm ID, EtOAc:Hex 1:9, 1 ml/min flow rate, 286 nm detection) every hour to monitor the disappearance of fraction e peak relative to naphthalene internal standard. This experiment was repeated twice and the half-life was determined to be 262 min and 268 min (Table S1). Page S20 of 138

21 VIII. Simulated half-life of fraction e The first-order rate constants of the rearrangements of fraction e were obtained from the calculated free energy of activation at 25 C at the M06-2X/6-31+G(d,p) level of theory (Scheme S1). The rearrangements and their rate constants were then inputted into the program KinTek_Explorer ( to simulate the reaction and determine the halflife of fraction e (Figure S5). k = k T ΔG B h e RT Page S21 of 138

22 ΔG = 22.9 kcal/mol k = s -1 I ( ΔG = 17.2 kcal/mol k = 1.6 s -1 ΔG = 11.0 kcal/mol k = s -1 ΔG = 23.3 kcal/mol k = s -1 J ( ΔG = 18.4 kcal/mol k = s -1 K ( Fraction e ΔG = 19.8 kcal/mol k = s -1 ΔG = 10.5 kcal/mol k = s -1 G ( ) ΔG = 18.9 kcal/mol k = s -1 L ( ΔG = 18.7 kcal/mol k = s -1 M ( ΔG = 20.0 kcal/mol k = s -1 ΔG = 12.7 kcal/mol k = s -1 H ( ΔG = 15.8 kcal/mol k = s -1 N ( Scheme S1. Calculated rate constants of rearrangements of fraction e. Page S22 of 138

$Figure S5. Half-life of fraction e. IX.$

23 Figure S5. Half-life of fraction e. IX. Simulated half-life of fraction e analogue without the ester The half-life of fraction e analogue without the ester was simulated according to the procedure applied to fraction e (Scheme S2 and Figure S6). Page S23 of 138

24 ΔG = 23.7 kcal/mol k = s -1 I ( ΔG = 16.9 kcal/mol k = 2.5 s -1 ΔG = 12.5 kcal/mol k = s -1 ΔG = 20.1 kcal/mol k = s -1 J ( ΔG = 16.1 kcal/mol k = s -1 K ( Fraction e analogue ΔG = 20.6 kcal/mol k = s -1 ΔG = 12.5 kcal/mol k = s -1 G ( ) ΔG = 16.5 kcal/mol k = 5.3 s -1 L ( ΔG = 20.3 kcal/mol k = s -1 M ( ΔG = 19.3 kcal/mol k = s -1 H ( ΔG = 12.8 kcal/mol k = s -1 ΔG = 19.0 kcal/mol k = s -1 N ( Scheme S2. Calculated rate constants of rearrangements of fraction e analogue. Page S24 of 138

25 Figure S6. Half-life of fraction e analogue. X. Computation details Monte Carlo Multiple Minimum (MCMM) conformational search using the OPLS_2005 force field was carried out for all isomers using the MacroModel application within the Maestro program from Schrödinger. The lowest energy conformation of the MCMM conformational search was optimized with DFT method at the B3LYP/6-31G(d) level of theory. For isomers involved within two generations of rearrangements from fraction e and its analogues without the ester group, their B3LYP/6-31G(d) geometries were further optimized with M06-2X functional and the 6-31+G(d,p) basis set. All transition state calculations were optimized with B3LYP/6-31G(d) and M06-2X/6-31+G(d,p). The geometries for M06-2X/6-31+G(d,p) calculation were taken from B3LYP/6-31G(d) optimized geometries. Frequency calculations were performed to verify minima and transition states (no imaginary frequency for minimum and one imaginary frequency for transition state). Transition states were also verified by animating the negative frequency. For computational simplicity, the isobutyl and ethyl groups were replaced by methyl groups. All DFT calculations were performed in the gas phase at 1 atm and K using the GAUSSIAN 09 program. Page S25 of 138

26 XI. Free energy comparison between B3LYP/6-31G(d) and M06-2X/6-31+G(d,p) Fraction e Page S26 of 138

27 Fraction e with the ester group replaced with a methyl group XII. Full reference for Gaussian 09 Gaussian 09, Revision A.02, 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. Nakatsuji, 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. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. 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, Page S27 of 138

28 XIII. Cartesian coordinates of calculated structures Isomer (fraction e) Ph OCO 2 Me Allyl CO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H C C C C H C H C H H H C O O C H Page S28 of 138

29 H H O C O O C H H H C H H C C H H H Isomer Ph Allyl OCO 2 Me CO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C Page S29 of 138

30 H C C C C H C H C H H H C O O C H H H C H C C H H H H O C O O C H H H Isomer OCO 2 Me Ph Allyl MeO 2 C RB3LYP/6-31G(d) Geometry Page S30 of 138

31 Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H C O O C H H H C H H C C H H H O C O O C H H H C Page S31 of 138

32 C C C H C H C H H H Isomer Ph OCO 2 Me Allyl MeO 2 C RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C H C C C H C O O C H H H Page S32 of 138

33 C H H C C H H H C C C C H C H C H H H O C O O C H H H Isomer Ph OCO 2 Me CO 2 Me Allyl RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H Page S33 of 138

34 C C H C C C C H C H C C C C H C H C H H H C H H C C H H H O C O O C H H H C O O C H H Page S34 of 138

35 H Isomer Ph CO 2 Me OCO 2 Me Allyl RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H C C C C H C H C H H H C H H C C Page S35 of 138

36 H H H C O O C H H H O C O O C H H H Isomer MeO 2 CO Ph Allyl CO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C H C C C Page S36 of 138

37 H O C O O C H H H C O O C H H C C C C H C H C H H H C H H C C H H H H Isomer Allyl Ph CO 2 Me MeO 2 CO RB3LYP/6-31G(d) Geometry Imaginary frequency: none Page S37 of 138

38 Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H O C O O C H H H C O O C H H H C H H C C H H H C C Page S38 of 138

39 C C H C H C H H H Isomer Allyl CO 2 Me Ph MeO 2 CO RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H O C O O C H H H Page S39 of 138

40 C C C C H C H C H H H C H H C C H H H C O O C H H H Isomer MeO 2 CO CO 2 Me Allyl Ph RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C Page S40 of 138

41 C H C C H C C C H O C O O C H H C C C C H C H C H H H C O O C H H C H H C C H H H H H Page S41 of 138

42 Isomer Ph CO 2 Me Allyl MeO 2 CO RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H O C O O C H H H C H H C C H H H C Page S42 of 138

43 C C C H C H C H H H C O O C H H H Isomer MeO 2 CO CO 2 Me Ph Allyl RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C C C H C H Page S43 of 138

44 O C O O C H H H C H H C C H H H C O O C H H H C C C C H C H C H H H Isomer Ph Allyl CO 2 Me OCO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Page S44 of 138

45 Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C H C C H C C O O C H H H C H H C C H H H C C C C H C H C H H Page S45 of 138

46 H O C O O C H H H Isomer Allyl CO 2 Me MeO 2 CO Ph RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H C C H C C H C C H C H C O O C H H H Page S46 of 138

47 O C O O C H H H C H H C C H H H C C C C H C H C H H H Isomer Allyl Ph OCO 2 Me CO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H Page S47 of 138

48 C C C C C C C H C H H C C H H H H O H C O O C H H H C C C C H C H C H H H C O O C H H Page S48 of 138

49 H Isomer Allyl OCO 2 Me CO 2 Me Ph RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C C C C C H H C H O C O O C H H H C C C C H C H C H Page S49 of 138

50 H H C H H C C H H H C O O C H H H Isomer MeO 2 CO CO 2 Me Allyl Ph RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C H C C C H O Page S50 of 138

51 C O O C H H H C H H C C H H H C O O C H H H C C C C H C H C H H H Isomer MeO 2 CO Allyl Ph MeO 2 C RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree Page S51 of 138

52 C C C C C H H C C H C C H H C H C C C C H C H C H H H C H H C C H H H O C O O C H H Page S52 of 138

53 H C O O C H H H Isomer MeO 2 C OCO 2 Me Ph Allyl RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H C C H H C C H H C C H C C C C C H C H C Page S53 of 138

54 H H H O C O O C H H H C O O C H H H C H H C C H H H Isomer MeO 2 C Ph Allyl OCO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C C C H Page S54 of 138

55 H C C H H C C H H C C O O C H H H C C C C H C H C H H H C H H C C H H H O C O O C H H Page S55 of 138

56 H Isomer MeO 2 CO Allyl Ph CO 2 Me RB3LYP/6-31G(d) Geometry Imaginary frequency: none Sum of electronic and thermal Free Energies= Hartree C C C H H H C C H C C H C C H C C H H C C H H H O C O O C H H H Page S56 of 138

Electronic Supplementary Information (ESI) for Chem. Commun.

page S1 Electronic Supplementary Information (ESI) for Chem. Commun. Nitric oxide coupling mediated by iron porphyrins: the N-N bond formation step is facilitated by electrons and a proton Jun Yi, Brian