Reversing the Direction in a Light-Driven Rotary. Molecular Motor

Transcription

1 SUPPLEMENTARY INFORMATION Reversing the Direction in a Light-Driven Rotary Molecular Motor Nopporn Ruangsupapichat, a Michael M. Pollard a,b, Syuzanna R. Harutyunyan a and Ben L. Feringa* a a Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, Groningen 9747AG, The Netherlands. b Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, Canada M3J 1P3. B.L.Feringa@rug.nl nature chemistry 1

2 supplementary information General Remarks. Chemicals were purchased from Aldrich, Acros, Fluka or Merck; solvents were reagent grade, distilled and dried before use according to standard procedures. All reactions were performed under an atmosphere of N 2. Column chromatography was performed on silica gel (Aldrich 60, mesh). 13 C NMR spectra were recorded on a Varian AMX400 (100 MHz). 1 H NMR spectra were recorded on a Varian VXR-300 (300 MHz) or a Varian AMX400 (400 MHz). Chemical shifts are denoted in δ-unit (ppm) relative to CDCl 3 ( 1 H δ = 7.26, 13 C δ = 77.0) and DMSO-d6 ( 1 H δ = 2.54). For 1 H NMR spectroscopy, the splitting parameters are designated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad), dd (double doublet), dt (doublet of triplets). MS (EI) and HRMS (EI) spectra were obtained with JEOL JMS-600 spectrometer. Melting points are taken on a Büchi Melting Point B-545 apparatus. UV/VIS measurements were performed on a Hewlett-Packard HP 8453 FT spectrophotometer. CD spectra were recorded on a JASCO J-715 spectropolarimeter using Uvasol-grade solvents (Merck). HPLC analyses were performed on a Waters HPLC system equipped with a 600E solvent delivery system and a 996 Photodiode Array Detector. Preparative HPLC was performed on a preparative Gilson HPLC system consisting of a 231XL sampling injector, a 306 (10SC) pump, an 811C dynamic mixer, an 805 manometric module, with a 119 UV-VIS detector and a 202 fraction collector, using the (chiral) columns as indicated. Elution speed was 1 ml min -1. Irradiation experiments were performed using a Spectroline model ENB-280C/FE lamp at λ = 312 nm, ± 30 nm. Samples irradiated for 1 H NMR spectroscopic analysis were placed 2-3 cm from the lamp. Photostationary states were determined by monitoring composition changes with respect to time by taking UV/Vis spectra or 1 H NMR spectra at distinct intervals until no additional changes were observed. Thermal behavior of a reversible molecular motor 1 As was the case of other motors with a methyl substituent at the 3 position, the determination of kinetic parameters of the helix inversion from less-stable isomer to stable isomer was slightly more complicated compared to previous molecular motor systems with substitution at the 2 -position due to the fact that there is a competing minor backward thermal helix inversion under the experimental conditions used. In 2 nature chemistry

3 supplementary information a similar 1 H NMR measurement to that described above, the thermal helix inversion step was proven by heating a mixture of less-stable and stable motor 1 eq (62: 38) at 80 C for 6h under conditions of continuous irradiation, and also by heating pure stable motor 1 eq at 80 C for 6 h. In both cases, a ratio of the stable 1 eq to less-stable motor 1 ax of 81:19 was observed (Figure). From this data we have determined and assigned k 1 for the energetically downhill forward helix inversion (from less-stable to stable) rate and k 2 for the energetically uphill backward helix inversion (from stable to less-stable) rate. Certainly, these rate constants are related through the equilibrium constant (K= k 1 /k 2 ) (Fig. S1). 1 Supplementary Figure S1. Thermal helix inversion pathway of the molecular motor 1. A detailed kinetic study of the thermal helix inversion of pure unstable form was performed based on 1 H NMR measurements in DMSO-d 6 at 4 different temperatures (Fig. S2). 1 Heating at 80 C the mixture of stable and less-stable form, pure stable or pure unstable form of motor 1 all provided similar ratio of stable and unstable form (81:19). nature chemistry 3

4 supplementary information Supplementary Figure S2. 1 H NMR measured kinetic data (in DMSO) for thermal helix inversion step of molecular motor 1 at four different temperatures (conversion in time of mole fraction). Analysis of kinetic data obtained for the thermal isomerization processes of molecular motor 1 using 1 H NMR spectroscopy experiments revealed the value of rate constants k 1 and k 2 and the ratio of stable to less-stable isomers (Table S1). Supplementary Table S1. The equilibrium constant (K) between stable isomer (1 eq ) and less-stable isomer (1 ax ) at different temperatures. a Entry T ( C) Ratio b of 1 eq : 1 ax k 1 (less-stable to stable)(s -1 ) k 2 (stable to less-stable)(s -1 ) K R 2 Chi-square :8 (6.1±0.5) 10-3 (5.3±0.5) :11 (9.2±0.7) 10-3 (1.2±0.1) :15 (4.7±0.2) 10-2 (8.4±0.3) :16 (9.9±0.4) 10-2 (1.9±0.1) a) 1 H NMR measurements of pure less-stable isomer were performed in DMSO-d 6 b) The ratios are calculated from the data graph presented in Figure S2. By extrapolation from this data, the half-life (t 1/2 ) at rt of the less-stable 1 ax to stable 1 eq was calculated to be 22 d. 4 nature chemistry

5 supplementary information Base catalyzed epimerization of a reversible molecular motor 1 After irradiation of racemic motor 1 (dichloromethane, rt, λ= 312 nm), the mixture of the less-stable isomer 1 ax and the stable isomer 1 eq was separated by column chromatography. A racemic mixture of pure less-stable isomer 1 ax ( M) was stirred with a variety of bases and solvents during 3-72 h at rt, yielding mixtures of stable and less-stable 1 (Table S2). The best conditions found for the epimerization involve the treatment with sodium tert-pentoxide (entry 7). Supplementary Table S2. Base-catalyzed epimerization of less-stable isomer (1 ax ) to stable isomer (1 eq ) at rt. entry Base/Solvent Time (h) Ratio of less-stable 1 ax : stable 1 eq 1 DBU (0.5 eq.)/ Toluene :0 2 LDA (1.2 eq.)/ THF (-78ºC) 5 side product 3 NaOMe (0.5 eq.)/ MeOH 24 92:8 4 t-buok (1 eq.)/ DCM and t-buoh 72 41:59 5 t-buok (3 eq.)/ DCM and t-buoh 72 38:62 6 t-buok (10 eq.)/ DCM and t-buoh 72 15:85 7 t-pentona (0.5 eq.)/ t-pentoh 25 98:2 8 t-pentona (1 eq.)/ t-pentoh 15 9:91 9 t-pentona (3 eq.)/ t-pentoh 15 8:92 10 t-pentona (5 eq.)/ t-pentoh 15 8:92 11 t-pentona (1 eq.)/ t-pentoh 3 62:38 12 t-pentona (1 eq.)/ t-pentoh a 3 48:52 a) 1 eq. of 15-crown-5-ether was added after base. CD and HPLC Monitoring of the Rotary Cycle. All photochemical experiments were carried out using a Spectroline model ENB-280C/FE lamp at λ = 312 nm, ± 30 nm. For analytical HPLC and CD analysis, samples irradiated were placed 2-3 cm from the lamp. Both stable enantiopure of (3 S)-(M)-1 (1 mg) and (3 R)-(P)-1 (1 mg) were dissolved in 1 ml of n-heptane and then were irradiated at λ 312 nm for 40 min. The thermal helix inversion process of both cases of less-stable (3 S)-(P)-1 and (3 R)-(M)-1 were heated at 80ºC for 6 h. For base-catalyzed nature chemistry 5

6 supplementary information epimerization process, both the enantiopures of stable (3 S)-(M)-1 (1 mg) and (3 R)-(P)-1 (1 mg) in 1 ml of n-heptane were irradiated at λ 312 nm for 40 min and then concentrated in vacuo to give the mixture of less-stable 1 and stable 1. The samples were dissolved in 0.5 ml of tert-amyl alcohol and added 0.7 mg of sodium tert-pentoxide, left stirring for 15 h at rt. The mixtures were filtrated trough SiO 2 and concentrated in vacuo to provide the samples for analytical HPLC. Characterization of Stable Molecular Motor 1 with preparative HPLC 9-(N,N-Dimethyl-3 -carboxamide-2,3 -dihydro-1 H-naphtho[2,1-b]-thiopyran-1 -ylidene)-9hthioxanthene ((3 S)-(M)-1 and (3 R)-(P)-1). After a racemic mixture of alkene (1) was obtained as a yellow solid, the resolution was completed by chiral HPLC using chiralcel AD column and a mixture of n-heptane:2-propanol (85:15) as the eluent. The first eluted fraction (t = 8.18 min) was (3 S)-(M)-1 (CD (dichloromethane): λ max (Δε) 244 (-46.6), 280 (-97.1), 322 (+30.8), 346 (+29.7)) and the second fraction (t = min) was (3 R)-(P)-1 (CD (dichloromethane): λ max (Δε) 244 (+42.0), 282 (+94.6), 322 (- 29.9), 346 (-28.7)). The different stereoisomers were analyzed by CD spectroscopy in which (M)- and (P)-helicity could be assigned by comparison with related molecular motor. 2 Experimental Section for the Synthesis of Molecular Motor 1. 3-Carboxyl-2,3-dihydro-1H-naphtho[2,1-b]thiopyran-1-one (3). A mixture of naphthalene-2-thiol (2) (6.00 g, 37.4 mmol) and maleic anhydride (3.67 g, 37.4 mmol) in toluene (180 ml) was stirred at 50 o C. After all of the material was dissolved, triethylamine (2 drops) in toluene (5 ml) was added over 2 van Delden, R. A., ter Wiel, M. K. J., de Jong, H., Meetsma, A. & Feringa, B. L. Exploring the boundaries of a lightdriven molecular motor design: new sterically overcrowded alkenes with preferred direction of rotation. Org. Biomol. Chem. 2, (2004). 6 nature chemistry

7 supplementary information 10 min keeping the temperature below 70 o C. After stirring at 70 o C for 20 min, the solvent was concentrated under reduced pressure to provide crude 3-(naphthalen-2-ylthio)dihydrofuran-2,5-dione. The residue was dissolved in dichloromethane (150 ml) and the solution cooled with an ice bath. Aluminum trichloride (5.57 g, 41.9 mmol) was added and the mixture was stirred at rt for 1.5 h. The mixture was diluted in dichloromethane (150 ml) and poured into ice-cold conc HCl (30 ml). The organic layer was separated, and the aqueous layer was extracted several times with dichloromethane. The combined organic extract was washed with water (2 200 ml), aqueous sodium bicarbonate (200 ml), brine (200 ml), dried (Na 2 SO 4 ) and concentrated in vacuo to give the crude product. Purification by column chromatography (silica gel; acetic acid: ethyl acetate: pentane = 5:25:70 as an eluent, R f = 0.27) yielded acid 3 (6.47 g, 25.1 mmol, 67 %) as a light yellow liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 4.18 (dd, J= 7.7, 5.1 Hz, 1H), 7.19 (d, J= 8.8 Hz, 1H), 7.42 (dt, J= 7.0, 1.1 Hz, 1H), 7.58 (dt, J= 7.0, 1.8 Hz, 1H), 7.68 (dd, J= 8.4, 1.5 Hz, 1H), 7.74 (d, J= 8.4 Hz, 1H), 9.16 (d, J= 8.8 Hz, 1H), (br s, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 41.9 (CH), 42.8 (CH 2 ), (CH), (C), (CH), (CH), (CH), (CH), (C), (C), (CH), (C), (C), (C); IR (Neat): ν max (cm -1 ) = 3060 (acid O-H), 2923 (CH 2 ), 2890 (CH), 1696 (br, acid C=O), 1663 (C=O), 1585 (Ar C=C), 1200 (C-CO-C); EI MS: m/z (%): 258 (73.1, M + ), 186 (100, [M- CH 2 CHC(O)OH] + ), 158 (27.8, [M- C(O)CH2CHC(O)OH] + ); HRMS (EI): m/z calcd for C 14 H 10 O 3 S: , found N,N-Dimethyl-3-carboxamide-2,3-dihydro-1H-naphtho[2,1-b]thiopyran-1-one (4). 1-[3- (Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (7.58 g, 39.5 mmol) and N,Ndiisopropylethylamine (4.87 ml, 27.9 mmol) were added to an ice-cold solution of dimethylamine hydrochloride (2.28 g, 27.9 mmol), acid 3 (6.00 g, 23.3 mmol), and 1-hydroxybenzotriazole (3.77 g, 27.9 mmol) in dichloromethane (150 ml). The mixture was stirred for 18 h at rt. The solvent was evaporated under reduced pressure, and the remaining slurry was diluted with ethyl acetate (200 ml). The resultant organic solution was washed with ice-cold water (200 ml), aqueous ammonium chloride (200 ml), and aqueous sodium bicarbonate (200 ml), brine (200 ml), dried (Na 2 SO 4 ) and concentrated nature chemistry 7

8 supplementary information in vacuo. The residue was purified by flash chromatography on silica gel (ethyl acetate: pentane = 1:4 as an eluent, R f = 0.38) to afford the amide 4 as a yellow foam (5.50 g, 19.3 mmol, 83%); mp C. 1 H NMR (400 MHz, CDCl 3 ) δ 2.98 (s, 3H), 3.15 (s, 3H), 3.17 (dd, J= 16.5, 3.7 Hz, 1H), 3.42 (dd, J= 16.5, 9.5 Hz, 1H), 4.44 (dd, J= 9.5, 3.7 Hz, 1H), 7.24 (dt, J= 8.4, 2.2 Hz, 1H), 7.44 (dt, J= 8.0, 1.0 Hz, 1H), 7.60 (dt, J= 8.8, 1.5 Hz, 1H), 7.74 (d, J= 8.0 Hz, 1H), 7.80 (dd, J= 8.4, 1.1 Hz, 1H), 9.27 (d, J= 8.8 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 36.2 (CH 3 ), 37.6 (CH 3 ), 40.2 (CH), 44.0 (CH 2 ), (CH), (C), (CH), (CH), (CH), (CH), (C), (C), (CH), (C), (C), (C); IR (Neat): ν max (cm -1 ) = 2931 (CH 2 ), 2904 (CH), 1634 (amide C=O), 1593 (Ar C=C), 1214 (C-CO-C), 671 (OCN); EI MS: m/z (%): 285 (100, M + ), 213 (26.1); HRMS (EI): m/z calcd for C 16 H 15 O 2 NS: , found N,N-Dimethyl-3-carboxamide-2,3-dihydro-1H-naphtho[2,1-b]thiopyran-1-one hydrazone (5). To a solution of amide 4 (1.00 g, 3.50 mmol) in ethanol (15 ml) was added hydrazine monohydrate (1.0 ml, 21.1 mmol). The solution was heated to 80 o C for 4 h and then allowed to cool to rt. Water (30 ml) was added, and the mixture was extracted with ethyl acetate (3 50 ml), the organic layers were combined, washed with brine (150 ml), dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; methanol: t-butyl methyl ether: dichloromethane = 5:15:80 as an eluent, R f = 0.26) to yield one isomer of the hydrazone 5 as a yellow foam (0.58 g, 1.93 mmol, 55%). 1 H NMR (400 MHz, CDCl 3 ) δ 3.00 (s, 3H), 3.03 (dd, J= 6.6, 4.4 Hz, 1H), 3.14 (s, 3H), 3.47 (dd, J= 10.3, 6.6 Hz, 1H), 4.10 (dd, J= 10.3, 4.4 Hz, 1H), 5.77 (br s, 2H), 7.31 (d, J= 8.8 Hz, 1H), 7.40 (dt, J= 7.0, 1.1 Hz, 1H), 7.48 (dt, J= 7.3, 1.1 Hz, 1H), 7.63 (d, J= 8.4 Hz, 1H), 7.74 (d, J= 8.1 Hz, 1H), 8.71 (d, J= 8.8 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 32.5 (CH 2 ), 36.2 (CH 3 ), 37.7 (CH 3 ), 42.5 (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C); IR (Neat): ν max (cm -1 ) = 3049 (N-H), 2922 (CH 2 ), 2852 (CH), 1644 (amide C=O), 1589 (Ar C=C); EI MS: m/z (%): 299 (49.4, M + ), 238 (72.7), 227 (100), 210 (50.3); HRMS (EI): m/z calcd for C 16 H 17 ON 3 S: , found nature chemistry

9 supplementary information Dispiro[N,N-dimethyl-3-carboxamide-2,3-dihydro-1H-naphtho[2,1-b]-thiopyran-1,2 -thiirane- 3,9 -(9 H-thioxanthene)] (8). A solution of hydrazone (5) (0.55 g, 1.8 mmol) in DMF (10 ml) was cooled to -50 o C and iodobenzene diacetate (0.59 g, 1.8 mmol) in DMF (2 ml) was added. After stirring for approximately 3 min to generate diazo compound 6, a solution of 9H-thioxanthene-9-thione (7) (0.331 g, 1.45 mmol) in DMF (5 ml) was added and the cooling bath removed. The reaction mixture was left stirring at rt for 5 h. Additional ethyl acetate (50 ml) was added and the mixture was washed with water (5 50 ml) and, brine (150 ml), dried (Na 2 SO 4 ) and concentrated in vacuo to give the crude product. Column chromatography (silica gel; ethyl acetate: pentane = 1:4 as an eluent, R f = 0.45) provided episulfide 8 (0.50 g, 1.0 mmol, 55 %) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 2.41 (dd, J= 13.6, 7.7 Hz, 1H), 2.68 (s, 3H), 2.80 (s, 3H), 3.15 (dd, J= 13.6, 9.9 Hz, 1H), 3.41 (dd, J= 10.3, 8.1 Hz, 1H), 6.35 (t, J= 7.3 Hz, 1H), 6.76 (t, J= 7.3 Hz, 1H), 6.93 (d, J= 8.4 Hz, 1H), 7.04 (d, J= 7.7 Hz, 1H), 7.11 (d, J= 8.1 Hz, 1H), (m, 4H), (m, 1H), 7.51 (t, J= 7.0 Hz, 1H), 7.56 (d, J= 8.1 Hz, 1H), (m, 1H), 9.18 (d, J= 8.8 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 36.1 (CH 3 ), 36.9 (CH 3 ), 38.4 (CH 2 ), 38.7 (CH), 58.1 (C), 59.2 (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (CH), (C), (CH), (C), (CH), (C), (C), (C), (C), (C), (C); IR (Neat): ν max (cm -1 ) = 2909 (CH 2 ), 2842 (CH), 1654 (amide C=O), 1582 (Ar C=C), 1455 (Ar C=C), 734 (Ar C-H deformation); EI MS: m/z (%): 497 (63.6, M + ), 463 (100), 269 (33.3); HRMS (EI): m/z calcd for C 29 H 23 ONS 3 : , found (N,N-Dimethyl-3 -carboxamide-2,3 -dihydro-1 H-naphtho[2,1-b]-thiopyran-1 -ylidene)-9hthioxanthene (1). A solution of episulfide (8) (258 mg, mmol) was heated at 80 C in p-xylene (5 ml) in the presence of triphenylphosphine (163 mg, 0.62 mmol) for 12 h. After cooling to rt, the p- xylene was removed under reduced pressure and the remaining oil was purified by column chromatography (silica gel; ethyl acetate: pentane = 1:4, R f = 0.42) after which a racemic mixture of alkene 1 was obtained as a yellow solid (222 mg, 0.48 mmol, 92 %); mp C. 1 H NMR (400 MHz, CDCl 3 ) δ 2.83 (dd, J= 12.9, 10.6 Hz, 1H), 3.05 (s, 3H), 3.29 (s, 3H), 3.51 (dd, J= 13.2, 7.7 Hz, nature chemistry 9

10 supplementary information 1H), 4.72 (dd, J= 10.6, 7.7 Hz, 1H), (m, 2H), 6.80 (dt, J= 7.7, 1.5 Hz, 1H), 7.05 (dt, J= 7.0, 1.5 Hz, 1H), 7.16 (dt, J= 7.0, 1.1 Hz, 1H), (m, 4H), (m, 5H); 13 C NMR (100 MHz, CDCl 3 ) δ 32.6 (CH 2 ), 36.5 (CH 3 ), 37.6 (CH 3 ), 43.5 (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C); IR (Neat): ν max (cm -1 ) = 2918 (CH 2 ), 2847 (CH), 1646 (R 1 R 2 C=CR 3 R 4 ), 1430 (Ar C=C), 740 (Ar C-H deformation); EI MS: m/z (%): 465 (96.0, M + ), 392 (36.0), 306 (48.0), 197 (100); HRMS (EI): m/z calcd for C 29 H 23 ONS 2 : , found (N,N-Dimethyl-3 -carboxamide-2,3 -dihydro-1 H-naphtho[2,1-b]-thiopyran-1 ylidene)-9hthioxanthene (less-stable 1 ). A solution of racemic mixture of stable 1 (126 mg, mmol) in dichloromethane (10 ml) was irradiated for 40 min at rt with an ENB-280C/FE lamp at λ 312 nm. After irradiation, TLC analysis indicated the conversion of (±)-stable 1 to the (±)-less-stable 1 ((3 S)- (P)-1 and (3 R)-(M)-1 ). Column chromatography (silica gel; ethyl acetate: pentane = 15:85, R f = 0.47) allowed separation of the (±)-less-stable 1 (70 mg, 0.15 mmol, 56%) from the (±)-stable 1, to provide a yellow solid; mp C. 1 H NMR (400 MHz, CDCl 3 ) δ 2.62 (dd, J= 12.5, 8.1 Hz, 1H), 3.10 (s, 3H), 3.11 (s, 3H), (m, 2H), (m, 2H), 6.71 (dt, J= 8.1, 1.8 Hz, 1H), 7.07 (t, J= 7.7 Hz, 1H), 7.19 (dt, J= 7.7, 0.7 Hz, 1H), (m, 2H), 7.44 (dt, J= 6.2, 1.1 Hz, 1H), (m, 5H), 8.17 (d, J= 7.7 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 35.8 (CH 2 ), 36.4 (CH 3 ), 37.7 (CH 3 ), 47.2 (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), one (CH) absorption of an aromatic proton was not observed (overlapping signal); IR (Neat): ν max (cm -1 ) = 2922 (CH 2 ), 2850 (CH), 1644 (R 1 R 2 C=CR 3 R 4 ), 1438 (Ar C=C), 740 (Ar C-H deformation); EI MS: m/z (%): 465 (83.3, M + ), 392 (30.8), 306 (42.8), 197 (100); HRMS (EI): m/z calcd for C 29 H 23 ONS 2 : , found nature chemistry

11 supplementary information Supplementary Figure S3. 1 H NMR Spectrum (400 MHz, CDCl3) of compound 3. Supplementary Figure S4. 13 C NMR Spectrum (100 MHz, CDCl3) of compound 3. nature chemistry 11

12 supplementary information Supplementary Figure S5. APT NMR spectrum (100 MHz, CDCl3) of compound 3. Supplementary Figure S6. 1 H NMR Spectrum (400 MHz, CDCl3) of compound nature chemistry

13 supplementary information Supplementary Figure S7. 13 C NMR Spectrum (100 MHz, CDCl3) of compound 4. Supplementary Figure S8. APT NMR spectrum (100 MHz, CDCl3) of compound 4. nature chemistry 13

14 supplementary information Supplementary Figure S9. 1 H NMR Spectrum (400 MHz, CDCl3) of compound 5. Supplementary Figure S C NMR Spectrum (100 MHz, CDCl3) of compound nature chemistry

15 supplementary information Supplementary Figure S11. APT NMR spectrum (100 MHz, CDCl3) of compound 5. Supplementary Figure S12. 1 H NMR Spectrum (400 MHz, CDCl3) of compound 8. nature chemistry 15

16 supplementary information Supplementary Figure S C NMR Spectrum (100 MHz, CDCl3) of compound 8. Supplementary Figure S14. APT NMR spectrum (100 MHz, CDCl3) of compound nature chemistry

17 supplementary information Supplementary Figure S15. 1 H NMR Spectrum (400 MHz, CDCl3) of compound stable 1. Supplementary Figure S C NMR Spectrum (100 MHz, CDCl3) of compound stable 1. nature chemistry 17

18 supplementary information Supplementary Figure S17. APT NMR spectrum (100 MHz, CDCl3) of compound stable 1. Supplementary Figure S18. 1 H NMR Spectrum (400 MHz, CDCl3) of compound less-stable nature chemistry

19 supplementary information Supplementary Figure S C NMR Spectrum (100 MHz, CDCl3) of compound less-stable 1. Supplementary Figure S20. APT NMR spectrum (100 MHz, CDCl3) of compound less-stable 1. nature chemistry 19