Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 Enantiomerically Enriched trans-Diols from Alkenes in One Pot: A Multicatalyst Approach Radim Hrdina, Christian E. Müller, Raffael C. Wende, Lukas Wanka, and Peter R. Schreiner* Justus-Liebig-Universität, Institut für Organische Chemie, Heinrich Buff-Ring 58, D-35392, Germany [email protected] Electronic Supporting Information Contents 1. General remarks 2 2. Synthesis of the peptide based catalysts 2 3. Catalysis and description of the 1,2-diols and the monoacetyl-1,2-diols 16 4. Additional Scheme S1 29 S1 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 1. General remarks Unless otherwise noted, chemicals were purchased from Acros Organics, Alfa Aesar, Aldrich, Lancaster, Merck, Novabiochem or Fluka at the highest purity grade available and were used without further purifications. All solvents were distilled prior to use. Toluene and CHCl were 3 distilled from appropriate drying agents prior to use and stored under argon atmosphere. Acetic anhydride was distilled prior to use and stored in a Schlenk tube. All catalytic reactions were carried out under an argon atmosphere employing oven- and flame-dried glassware. Column chromatography was conducted using J.T. Baker silica gel (0.063 – 0.200 mm) or, for flash column chromatography, Merck silica gel 60 (0.040 – 0.063 mm), respectively. TLC R f values are reported. 1H and 13C NMR spectra were recorded on Bruker AV600, AV400 or AV200 spectrometers, respectively, using TMS as the internal standard with chemical shifts given in ppm relative to TMS or the respective solvent residual peaks. Infrared spectra were recorded on a Bruker IFS25 spectrometer. MS / HRMS were recorded on a Finnigan MAT95 sectorfield spectrometer; ESI mass spectra on a Finnigan LCQDuo spectrometer using methanol solutions of the respective compounds. High resolution ESI mass spectrometry was performed on a Thermo Scientific LTQ FT Ultra hybrid mass spectrometer using methanol solutions of the respective compounds. Optical rotation was measured by using a Jasco P- 2000 polarimeter. GC analyses were performed by using Hewlett Packard 5890 and Carlo Erba 2900 gas chromatographs. 2. Synthesis of the peptide catalysts Peptides A–G were synthesized in solution using Boc-strategy and EDC/HOBt mediated couplings. The general peptide synthesis is exemplarily given for F. Synthesis of Boc-L-(π-Me)-His-AGly-L-Cha-L-Phe-βAsp-(OBzl) : 2 S2 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 Procedure for the EDC/HOBt peptide coupling in solution: An equimolar ratio of the N- Boc-protected amino acid (4 mmol) and the peptide fragment (4 mmol), 1.1 eq of EDC (4.4 mmol) and 1.1 eq of HOBt (4.4 mmol) were dissolved in dry dichloromethane. Then 1.1 eq of triethyl amine (4.4 mmol) were added and the solution was stirred overnight. The reaction mixture was added to 300 mL ethyl acetate and extracted with a 0.5 M citric acid solution (100 mL) and a saturated NaHCO solution (100 mL). The organic phase was dried over 3 MgSO and the evaporation of the solvent gave the product. The same strategy was used for 4 the esterification of Boc- βAsp-OBzl with benzylalcohol to prepare the starting material Boc- βAsp-(OBzl) . All peptide fragments were used for the next coupling step without further 2 purification. The last coupling step with the peptide and N-Boc-π-Me-His was realized with a twofold excess of coupling reagents 2.2 eq of EDC (8.8 mmol), 2.2 eq of HOBt (8.8 mmol) and 2.2 eq of triethyl amine (8.8 mmol). Procedure for the cleavage of the Boc-protecting group: The peptide (4 mmol) was dissolved in a solution of 4 M HCl in 1,4-dioxane (4 mL) and stirred for 30 min. The excessive HCl was removed by flushing the reaction mixture with argon for 30 min. After evaporation of the solvent under reduced pressure the deprotected peptides were used for further peptide coupling steps without purification. After the last coupling step the crude peptide was purified by silica gel column chromatography. Eluting with CHCl /MeOH 9:1 afforded 2.3 g (2.18 mmol, 54 %) of 3 colorless pentapeptide Boc-L-(π-Me)-His-AGly-L-Cha-L-Phe-βAsp-(OBzl) . 2 1H NMR (400 MHz, CDCl ): δ/ppm = 0.75 – 1.00 (m, 2H), 1.05 – 1.30 (m, 6H), 1.42 (s, 9H), 3 1.43 – 1.57 (m, 1H), 1.57 – 1.75 (m, 12H), 1.80 – 2.00 (m, 6H), 2.15 – 2.20 (m, 2H), 2.38 v 2.48 (m, 1H), 2.52 – 2.70 (m, 3H), 2.90 – 3.10 (m, 5H), 3.58 (s, 3H), 4.20 – 4.30 (m, 1H), 4.36 – 4.44 (m, 1H), 4.48 – 4.64 (m, 2H), 5. 01 – 5.13 (m, 4H), 5.35 – 5.45 (m, 1H), 6.80 – 6.95 (m, 3H), 7.10 – 7.20 (m, 3H), 7.20 – 7.28 (m, 2H), 7.29 – 7.38 (m, 8H), 7.39 – 7.42 (m, 1H) 13C NMR (100 MHz, CDCl ): δ/ppm = 27.0, 28.3, 29.1, 31.5, 32.4, 33.6, 34.2, 35.1, 37.5, 3 37.7, 37.9, 38.1, 39.3, 40.1, 40.2, 42.2, 42.5, 43.0, 51.2, 52.2, 54.4, 66.5, 66.6, 76.8, 77.1, 77.4, 80.3, 126.9, 127.3, 128.0, 128.2, 128.2, 128.3, 128.6, 128.7, 129.3, 135.5, 135.5, 136.5, 138.0, 155.4, 169.8, 169.9, 170.7, 170.7, 172.1, 176.9; S3 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 IR (KBr): /cm–1 = 3304, 3064, 3032, 2922, 2852, 1738, 1654, 1509, 1455, 1391, 1366, 1247, 1168, 1111, 1057, 1028, 910, 735, 698, 662, 498. ESI: m/z = 1056.6 [M+H]+; HR-ESI: m/z = 1056.5805 [M+H]+ (calc. m/z =1056.5805). S4 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 General procedure for the acetyl-protection of the N-terminus of the peptides: Prior to the acetyl introduction, the Boc protecting group of the peptide (1 mmol) was removed as described above, using 4 M HCl in 1,4-dioxane (2 mL). The excessive HCl was removed by flushing the reaction mixture with argon for 30 min. After evaporation of the solvent the deprotected peptide was dissolved in dry DCM (10 mL) by addition of Et N (20 mmol, 2.8 3 mL, 20 eq). The resulting solution was cooled to 0 °C and acetic anhydride (10 mmol, 945 µL, 10 eq) was added. The reaction mixture was allowed to warm to room temperature, while stirring for 1.5 h. The reaction mixture was then added to 300 mL ethyl acetate and extracted with 0.5 M citric acid solution (100 mL), saturated NaHCO solution (100 mL). The organic 3 phase was dried over MgSO and the evaporation of the solvent gave the product. The crude 4 product was purified by silica gel column chromatography eluting with CHCl /MeOH 9/1. 3 Procedure for the reductive benzylester-deprotection: The deprotection of the benzyl ester groups was performed by using 0.8 mmol of Boc-L-(π-Me)-His-AGly-L-Cha-L-Phe-βAsp- (OBzl) (844 mg) in 50 mL flask and 10% Pd/C (115 mg) in tBuOH (6 mL) under hydrogen 2 atmosphere for 48 h. The reaction mixture was then filtrated through a frit and two times through filtration paper. The solvent was evaporated under reduced pressure and peptide F was used for catalysis without additional purification (purity of the corresponding peptides were controlled by NMR and ESI). S5 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 For entire characterizations the peptides D, E, F were purified by HPLC (HP/Agilent 1050 equipment and a Restek Viva C18 column (21.2 ×250 mm, 5 µM, 300 Å) employing a gradient elution at 3.5 mL/min flow using gradients of eluent E1 (0.1% TFA in water) and eluent E2 (0.1% TFA in acetonitrile): 27-37% E2 in E1 for 20 min, to 52% E2 in E1 65 min., then to 90% E2 in 70 min and at 90% E2 until 75 min. 1H NMR (400 MHz, d -DMSO): δ/ppm = 0.69 – 0.92 (m, 2H), 0.98 – 1.22 (m, 5H), 1.33 (s, 6 9H), 1.38 – 1.51 (m, 2H), 1.53 – 1.69 (m, 10H), 1.69 – 1.78 (m, 2H), 1.80 – 2.05 (m, 6H), 2.05 – 2.21 (m, 2H), 2.90 – 3.00 (m, 5H), 3.83 (s, 3H), 4.20 – 4.35 (m, 3H), 4.38 – 4.50 (m, 1H), 6.80 – 7.00 (m, 1H), 7.15 – 7.30 (m, 6H), 7.30 – 7.50 (m, 2H), 7.55 – 7.75 (m, 2H), 8.05 – 8.15 (m, 1H), 8.95 (s, 1H), 12.30 (bm, 1H), 14.40 (bs, 1H). 13C NMR (100 MHz, d -DMSO): δ/ppm = 25.6, 25.8, 26.0, 26.4, 28.0, 28.7, 31.6, 33.1, 33.6, 6 34.9, 37.4, 37.5, 37.8, 38.0, 38.4, 41.8, 42.0, 43.1, 50.3, 51.5, 52.5, 53,4, 78.4, 118.0, 126.2, 127.9, 129.2, 130.9, 135.3, 137.4, 155.0, 169.2, 170.0, 171.9, 172.1, 172.1, 175.9. IR (KBr): /cm–1 = 3407, 3067, 2925, 2855, 1666, 1526, 1451, 1393, 1368, 1280, 1252, 1202, 1139, 1057, 888, 836, 800, 748, 722, 703, 627. ESI: m/z = 876.3 [M+H]+; HR-ESI: m/z = 876.4860 [M+H]+ (calc. m/z = 876.4866). S6 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 S7 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 1H NMR (400 MHz, d -DMSO): δ/ppm = 0.48 – 0.58 (m, 6H), 1.13 (s, 9H), 1.23 – 1.72 (m, 6 10H), 1.82 – 1.90 (m, 2H), 2.18 – 2.30 (m, 10H), 3.8 – 4.10 (m, 4H), 6.64 – 6.83 (m 2H), 7.08 (s, 1H), 7.36 (s, 1H), 7.76 – 7.80 (m, 2H), 8.74 (s, 1H), 12.30 (bm, 1H), 14.40 (bs, 1H). 13C NMR (100 MHz, d -DMSO): δ/ppm = 18.1, 19.2, 26.3, 28.0, 28.7, 30.7, 33.1, 34.8, 37.6, 6 38.0, 42.1, 43.1, 51.5, 52.5, 57.4, 78.4, 118.0, 130.9, 155.0, 169.3, 170.4, 172.0, 172.1, 175.4. IR (KBr): /cm–1 = 3305, 3140, 3074, 2917, 1667, 1523, 1455, 1394, 1369, 1252, 1202, 1057, 1024, 888, 836, 799, 722, 671, 627. ESI: m/z = 675.2 [M+H]+; HR-ESI: m/z = 675.3697 [M+H]+ (calc. m/z = 675.3712). S8 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 1H NMR (400 MHz, d -DMSO): δ/ppm = 0.48 – 0.70 (m, 2H), 0.75 – 1.00 (m, 4H), 1.09 – 6 1.80 (m, 22H), 1.85 – 1.93 (m, 2H), 2.20 – 2.42 (m, 8H), 2.44 – 2.80 (m, 5H), 4.03 – 4.09 (m, 1H), 4.25 – 4.45 (m, 3H), 6.90 – 7.21 (m, 7H), 7.46 – 7.52 (m, 2H), 7.94 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 7.8 Hz, 1H), 8.77 (s, 1H), 12.30 (bs, 1H), 14.40 (bs, 1H). 13C NMR (100 MHz, d -DMSO): δ/ppm = 25.8, 26.0, 26.4, 28.7, 31.5, 33.1, 33.6, 34.9, 35.9, 6 37.4, 37.5, 37.7, 38.5, 40.3, 41.8, 41.9, 48.6, 50.2, 51.0, 51.6, 53.1, 117.8, 126.2, 127.2, 127.9, 129.3, 130.7, 135.4, 137.4, 169.0, 169.2, 170.7, 171.6, 172.0, 172.2, 175.8. IR (KBr): /cm–1 = 3417, 3069, 2925, 2855, 1724, 1658, 1532, 1450, 1380, 1344, 1285, 1202, 1139, 1030, 900, 836, 800, 722, 702, 625. ESI: m/z = 804.3 [M+H]+; S9 Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2012 HR-ESI: m/z = 804.4291 [M+H]+ (calc. m/z = 804.4291). S10