Supporting Information

Transcription

1 Supporting Information S1

2 Reversible stereodivergent cycloaddition of racemic helicenes to [60]fullerene: a chiral resolution strategy Rosa M. Girón, Jiangkun Ouyang, Ludovic Favereau, Nicolas Vanthuyne, Jeanne Crassous,* Salvatore Filippone,* Nazario Martín* Contents 1. General Methods and Materials page S3 2. Experimental Procedures and Characterizations page S4 3. Representative NMR Spectra page S11 4. Representative Mass Spectra page S20 5. Representative HPLC Chromatograms page S21 6. Absorption and emission spectra page S25 7. References page S26 S2

3 1. General Methods and Materials The commercially available reagents and solvents were used without further purification. Iminoesters 2 1 were previously described in the literature. 1 H NMR and 13 C NMR spectra were recorded on a BRUKER AVANCE-300 and -700 in CDCl 3, or a BRUKER AVANCE AMX-700 in CDCl 3 at 23 C, and referenced to CDCl 3 ; coupling constants (J) are reported in Hz and the chemical shifts (δ) in ppm. Mass spectra was reported on a HP1100EMD (ESI). Reactions were monitored by thin-layer chromatography carried out on 0.2 mm TLC-aluminium sheets of silica gel (Merck, TLC Silica gel 60 F 254 ). Flash column chromatography was performed using silica gel ( mesh). For conversions and diastereomeric excesses, HPLC column Buckyprep (Waters) (4.6 x 250 mm, 5µm) was used and for enantiomeric excesses, chiral HPLC Chiralpak IC (4.6 x 250 mm, 5µm). All these values were monitored in a 320 nm spectrophotometer detector. Circular Dichroism (DC) measurements were carried out on a JASCO J-815 DC SPECTROMETER. 1 López-Pérez A, Adrio J, Carretero JC. The phenylsulfonyl group as a temporal regiochemical controller in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides. Angewandte Chemie (International ed. in English). 2009;48(2):340-3 S3

4 2.1 General procedure for the synthesis of carbo[6]helicene-2- carboxaldehyde 1 Carbo[6]helicene-2-carboxaldehyde 1 was prepared following a previously reported procedure. 2 Analytical chiral HPLC separation for carbo[6]helicene-2-carboxaldehyde 1 The sample is dissolved in chloroform, injected on the chiral column, and detected with an UV detector at 254 nm and with CD at 254 nm. The flow-rate is 1 ml/min. Column Mobile Phase t1 k1 t2 k2 α Rs Chiralpak IC Heptane / Isopropanol /chloroform(80/10/10) 6.04(+) (-) Chiralpak IC Heptane / Isopropanol /chloroform Signal: DAD1 C, Sig=254,4 Ref=off RT [min] Area Area% Capacity Factor Enantioselectivity Resolution (USP) Sum El Sayed Moussa, M.. Srebro, M.; Anger, E.; Vanthuyne, N.; Roussel; C.; Lescop, C.; Autschbach, J.; Crassous, J. Chirality, 2013; 25, S4

5 Semi-preparative separation for compound 1: Sample preparation: About 240 mg of compound 1 are dissolved in 27 ml of a mixture of hexane/isopropanol/chloroform 45/5/50. Chromatographic conditions: Chiralpak IC (250 x 10 mm), hexane / isopropanol / chloroform (80/10/10) as mobile phase, flow-rate = 5 ml/min, UV detection at 254 nm. Injections (stacked): 180 times 150 µl, every 2.5 minutes. Collection: the first eluted enantiomer is collected between 6 and 6.3 minutes and the second one between 7.1 and 7.5 minutes. First fraction: 71 mg of the first eluted enantiomer with ee > 99.5% RT [min] Area Area% Sum S5

6 Second fraction: 65 mg of the second eluted enantiomer with ee > 99% RT [min] Area Area% Sum General procedure for the synthesis of helicene α-iminoesters 2 The α-iminoesters 2 were synthesized according to the method described in literature. Synthesis of racemic tert-butyl (E)-N-[(2-carbo[6]helicene)methylene]glycinate (2) N CO 2 tbu tbuo 2 C N (M) (P) S6

7 The racemic iminoester 2 was prepared according to the general procedure by using carbo[6]helicene-2-carbaldehyde 3 (20 mg, mmol,) tert-butyl glycinate hydrochloride (14 mg, mmol), triethylamine (12 µl, mmol), and anhydrous sodium sulfate. Yellow solid (26 mg, 99%). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 11H), 7.68 (s, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.36 (s, 1H), 7.21 (t, J = 7.0 Hz, 1H), 6.69 (t, J = 7.7 Hz, 1H), δ 4.15 (d, J = 15.7 Hz, 1H), 4.03 (d, J = 16.0 Hz, 1H), 1.48 (s, 9H). 13 C NMR (75 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , , , , , , , , , , , , 81.61, 77.87, 77.44, 77.02, 62.88, HRMS (ESI + ) [M+H] + Calc. for C 33 H 28 NO 2 : 470,2120; found: 470, El Sayed Moussa M, Srebro M, Anger E, Vanthuyne N, Roussel C, Lescop C, Autschbach J, Crassous J, Chiroptical properties of carbo[6]helicene derivatives bearing extended π-conjugated cyano substituents. Chirality, (2013);25: S7

8 Synthesis of tert-butyl (E)-N-[M-(2- carbo[6]helicene)methylene]glycinate (M-2) The iminoester M-2 was prepared according to the general procedure by using M-carbo[6]helicene-2- carbaldehyde (20 mg, mmol,) tert-butyl glycinate hydrochloride (14 mg, mmol), triethylamine (12 µl, mmol), and anhydrous sodium sulfate. Yellow solid (25.5 mg, 96%). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 7.80 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.36 (s, 1H), 7.21 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 6.69 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), δ 4.16 (dd, J = 16.0, 1.2 Hz, 1H), 4.03 (dd, J = 16.0, 1.1 Hz, 1H), 1.48 (s, 9H). Synthesis of tert-butyl (E)-N-[P-(2-carbo[6]helicene)methylene]glycinate (P-2) The iminoester P-2 was prepared according to the general procedure by using P-carbo[6]helicene-2- carbaldehyde (20 mg, mmol,) tert-butyl glycinate hydrochloride (14 mg, mmol), triethylamine (12 µl, mmol), and anhydrous sodium sulfate. Yellow solid (25 mg, 94%). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 7.80 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.36 (s, 1H), 7.21 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H), 6.69 (ddd, J = 8.4, 7.0, 1.3 Hz, 1H), δ 4.16 (dd, J = 16.0, 1.1 Hz, 1H), 4.03 (dd, J = 16.1, 1.0 Hz, 1H), 1.48 (s, 9H). S8

9 2.3 General procedure for catalytic 1,3-dipolar cycloaddition of heliceneazomethine ylides and [60]fullerene Chiral ligand ( mmol) and metal salt ( mmol) were dissolved in toluene (3 ml). The solution was stirred for 1h at room temperature, and then, a solution of α-iminoester ( mmol). Finally, C 60 ( mmol). The reaction mixture was stirred for 2.5 h, and afterwards, it was quenched with a saturated ammonium chloride solution (20 ml). The mixture was extracted with toluene (3 x 20mL), and the combinated extracts were washed with brine (30 ml). The organic layer was dried over MgSO 4 and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (1) CS 2 / 2) CS 2 :DCM 100:1 to 10:1)). Synthesis of (2S,5S)-tert-butoxycarbonyl-5-(M-2-carbo[6]helicene)pyrrolidino [3,4:1,2][60]fullerene (M,S,S-4) The adduct M,S,S-4 was prepared according to the general procedure by using the catalytic system (R p )-Fesulphos (1 mg, mmol) and Cu(OAc) 2 (4 mg, mmol), tert-butyl (E)-N- [M-(2-carbo[6]helicene)methylene]glycinate M-2 (3.5 mg, mmol,) and C 60 (11 mg, mmol). Brown solid (7.2 mg, 83%). 1 H NMR (700 MHz, CDCl 3 ) δ 8.40 (s, 1H), 8.28 (d, J = 7.9 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), (m, 6H), 7.90 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.4 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 5.43 (s, 1H), 5.30 (s, 1H), 2.80 (s, 1H), 1.59 (s, 9H). 13 C NMR (176 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 83.12, 76.51, 73.72, HRMS (ESI + ) [M+H] + Calc. for C 93 H 28 NO 2 : 1190,2120; found: S9

10 Synthesis of (2S,5S)-tert-butoxycarbonyl-5-(P-2-carbo[6]helicene)pyrrolidino [3,4:1,2][60]fullerene (P,S,S-3) The adduct P,S,S-3 was prepared according to the general procedure by using the catalytic system (R p )- Fesulphos (1 mg, mmol) and Cu(OAc) 2 (4 mg, mmol), tert-butyl (E)-N-[P-(2- carbo[6]helicene)methylene]glycinate P-2 (3.5 mg, mmol,) and C 60 (11 mg, mmol).brown solid (9.8 mg, 92%). 1 H NMR (700 MHz, CDCl 3 ) δ 8.12 (s, 1H), 8.03 (d, J = 8.3 Hz, 2H), (m, 8H), 7.86 (d, J = 7.3 Hz, 1H), 7.73 (d, J = 8.5 Hz, 1H), (m, 1H), (m, 1H), 5.31 (s, 1H), 4.93 (s, 1H), 1.54 (s, 9H). 13 C NMR (176 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 83.56, 78.56, 74.76, 72.89, HRMS (ESI + ) [M+H] + Calc. for C 93 H 28 NO 2 : 1190,2120; found: S10

11 3. Representative NMR spectra 3.1. NMR spectra of α-iminoesters 2 1 H-NMR, 13 C-NMR, DEPT-135 spectra of tert-butyl (E)-N-[(2-carbo[6]helicene) methylene]glycinate (2) 1 H-NMR f1 (ppm) C-NMR / DEPT f1 (ppm) S11

12 1 H-NMR, spectrum of tert-butyl (E)-N-[(M-2-carbo[6]helicene)methylene] glycinate (M-2) f1 (ppm) H-NMR, spectrum of tert-butyl (E)-N-[(P-2-carbo[6]helicene)methylene] glycinate (P-2) f1 (ppm) S12

13 3.2. Representative NMR spectra of pyrrolidino[3,4:1,2][60]fullerene derivatives H-NMR, 13 C-NMR, DEPT-135, COSY, HMQC, HMBC spectra of (2S,5S)-tertbutoxycarbonyl-5-(M-2-carbo[6]helicene)pyrrolidino[3,4:1,2][60]fullerene (M,S,S- 4) 1 H-NMR S13

14 13 C-NMR / DEPT f1 (ppm) S14

15 S15 COSY f2 (ppm) Q07GR945-1A f2 (ppm) Q07GR945-1A-700

16 S16 HMQC f2 (ppm) Q07GR945-1A f2 (ppm) Q07GR945-1A-700

17 S17 HMBC f2 (ppm) f2 (ppm)

18 1 H-NMR, 13C-NMR and DEPT-135 spectra of (2S,5S)-tert-butoxycarbonyl-5-(P-2- carbo[6]helicene)pyrrolidino[3,4:1,2][60]fullerene (P,S,S-3) 1 H-NMR f1 (ppm) C-NMR / DEPT f1 (ppm) S18

19 1 H-NMR, spectrum of (2R,5R)-tert-butoxycarbonyl-5-(P-2-carbo[6]helicene) pyrrolidino[3,4:1,2][60]fullerene (P,R,R-4) f1 (ppm) H-NMR, spectrum of (2R,5R)-tert-butoxycarbonyl-5-(M-2-carbo[6]helicene) pyrrolidino[3,4:1,2][60]fullerene (M,R,R-3) f1 (ppm) S19

20 4. Representative Mass spectra Mass spectra of tert-butyl (E)-N-[(2-carbo[6]helicene) methylene]glycinate (2) Mass spectra of (2S,5S)-tert-butoxycarbonyl-5-(M-2- carbo[6]helicene)pyrrolidino[3,4:1,2][60]fullerene (M,S,S-4) Mass spectra of (2S,5S)-tert-butoxycarbonyl-5-(P-2- carbo[6]helicene)pyrrolidino[3,4:1,2][60]fullerene (P,S,S-3) S20

21 5. Representative HPLC chromatograms Buckyprep (Waters) (4.6 x 250 mm), toluene:acetonitrile:hexane 50:10:40, flow rate 1.00 ml/min. C 60 Figure S1. Diastereomeric ratio between (P,S,S)-3 (t R = 7.6 min) and (P,R,R)-4 (t R = 8.7 min) of enantioriched iminoester P-2 cycloaddition onto [60]fullerene. Buckyprep (Waters) (4.6 x 250 mm), toluene:acetonitrile:hexane 50:10:40, flow rate 1.00 ml/min. C 60 Figure S2. Diastereomeric ratio between (M,R,R)-3 (t R = 7.6 min) and (M,S,S)-4 (t R = 8.7 min) of enantioenriched iminoester M-2 cycloaddition onto [60]fullerene. S21

22 Buckyprep (Waters) (4.6 x 250 mm, 5µm), toluene:acetonitrile:hexane 50:10:40, flow rate 1.00 ml/min. C 60 Figure S3. Diastereomeric ratio of racemic iminoester 2 cycloaddition onto [60]fullerene. Chiralpak IC (4.6 x 250 mm, 5µm), hexane:isopropanol 97:3, flow rate 2.00 ml/min. Figure S4. Enantiomeric excess of diastereoisomer (M,S,S)-4/(P,R,R)-4. The main enantiomer is (M,S,S)-4 (t R = 7.1 min) while the enantiomer (P,R,R)-4, that usually is eluted at 15 min. is not detected. S22

23 Chiralpak IC (4.6 x 250 mm, 5µm), hexane:isopropanol 97:3, flow rate 2.00 ml/min. Figure S5. Enantiomeric excess of diastereoisomer, (M,R,R)-3 (t R = 14.4 min)/(p,s,s)-3 (t R = 7.8 min) Chiralpak IC (4.6 x 250 mm, 5µm), hexane:isopropanol 97:3, flow rate 2.00 ml/min. Figure S6. Racemic aldehyde 1. S23

24 Chiralpak IC (4.6 x 250 mm, 5µm), hexane:isopropanol 97:3, flow rate 2.00 ml/min. a) b) Figure S7. a)m-1. b) P-1. Chiralpak IC (4.6 x 250 mm, 5µm), hexane:isopropanol 97:3, flow rate 2.00 ml/min. C 60 Figure S8. Crude of retrocycloaddition of (P,S,S)-3. S24

25 Chiralpak IC (4.6 x 250 mm, 5µm), hexane:isopropanol 97:3, flow rate 2.00 ml/min. C 60 Figure S9. Crude of retrocycloaddition of (M,S,S) Absorption and emission spectra. Figure S10. Absorption and emission spectra of compounds 1 (black) and 3 (red) (excitation wavelength 350 nm, at this wavelength, the absorbance for the two compounds was 0.07) in dichloromethane. S25

26 7. References 1. López-Pérez, A.; Adrio, J.; Carretero, J. C. Angew. Chem. Int. Ed, 2009, 48, El Sayed Moussa, M.. Srebro, M.; Anger, E.; Vanthuyne, N.; Roussel; C.; Lescop, C.; Autschbach, J.; Crassous, J. Chirality, 2013; 25, S26