enantioselective desymmetrization of prochiral 1,3 ... · pdf file enantioselective...

Click here to load reader

Post on 28-Jun-2020

3 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

  • Enantioselective desymmetrization of prochiral 1,3-dinitropropanes via organocatalytic allylic alkylation

    Soumya Jyoti Singha Roy and Santanu Mukherjee*

    Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, INDIA

    [email protected]

    SUPPORTING INFORMATION: PART A

    General: Unless stated otherwise, all reactions were carried out with distilled and dried solvents under an atmosphere of N2 or argon, oven (120 °C) dried glassware with standard vacuum line techniques were used. Organic solvents used for carrying out reactions were dried using standard methods. All work up and purification were carried out with reagent grade solvents in air. Thin- layer chromatography was performed using Merck silica gel 60 F254 pre-coated plates (0.25 mm). Column chromatography was performed using silica gel (230-400 or 100- 200 mesh). Infrared (FT-IR) spectra were recorded on a Perkin Elmer Spectrum BX spectrophotometer in cm-1 and the bands are characterized as broad (br), strong (s), medium (m), and weak (w). NMR spectra were recorded on Bruker Ultrashield spectrometer at 400MHz (1H) and 100 MHz (13C). Chemical shifts are reported in ppm from tetramethylsilane (δ 0.00) with the solvent resonance as internal standard (CDCl3: δ 7.26, CD3OD: δ 3.31 for 1H-NMR and CDCl3: δ 77.0, CD3OD: δ 49.00 for 13C NMR). For 1H-NMR, data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, dd = double doublet, t = triplet, q = quartet, br = broad, m = multiplet), coupling constants (Hz) and integration. High-resolution mass spectrometry was performed on Micromass Q-TOF Micro instrument. Optical rotations were measured on JASCO P-1020 polarimeter. Melting points were measured using ANALAB µ-Thermocal 10 melting point apparatus. All melting points were measured in open glass capillary and values are uncorrected. Enantiomeric ratios were determined by HPLC analysis using chiral columns in comparison with authentic racemic materials. Aldehydes were not purified before use. Nitromethane and basic alumina was used as obtained by commercial suppliers. Ethyl acrylate was freshly distilled before use.

    Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2013

  • Singha Roy & Mukherjee, SI-Part-A, Page S-2  

    Preparation of 2-substituted 1,3-dinitropropanes:

    Procedure A: For the preparation of 1a, 1c-f, 1h-n modified literature1 procedure was followed.

    In an oven-dried round bottom flask fitted with a magnetic stir-bar, aldehyde (1.0 equiv.) was dissolved in nitromethane (25.0 equiv.). To this solution basic alumina (0.6 g/mmol of the aldehyde) was added; the resulting slurry was heated (at the temperature specified for the corresponding compounds) for required amount of time in an argon atmosphere. After completion of the reaction, the reaction mixture was allowed to attain room temperature; the alumina was then filtered off and the filtrate was concentrated to obtain, in all the cases, a thick oil. This was purified by silica gel (230-400 mesh) column chromatography. In most of the cases, the oil obtained after column purification, were crystallized/solidified using appropriate solvent system to obtain solid/crystalline dinitropropanes that were used for the catalytic reactions.

    1-(1,3-Dinitropropan-2-yl)-4-methylbenzene (1a): Reaction was performed at 105 °C for 12 h.

    Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 7-10% EtOAc/pet ether) afforded a red oil. This was subjected to solidification using EtOAc-toluene-pet ether (1:3:5) mixture at –20 °C for overnight to get 1a as a brownish solid (1.975 g, 8.802 mmol; 48% yield). Rf

    = 0.30 (25% EtOAc in pet ether); Melting point = 49-50 °C; FT-IR (KBr): ν 2921 (m), 1564 (s), 1557 (s), 1378 (s), 818 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.17 (d, J = 8 Hz; 2H), 7.10 (d, J = 8 Hz; 2H), 4.69-4.79 (m; 4H), 4.23-4.30 (m; 1H), 2.33 (s; 3H); 13C-NMR (100 MHz, CDCl3): δ 139.1, 131.0, 130.2, 127.2, 76.8, 41.4, 21.1; HRMS (ESI+): Calculated for C10H12N2O4Na ([M+Na]+): 247.0695, found: 247.0695. 1-Chloro-4-(1,3-dinitropropan-2-yl)benzene (1c): Reaction was performed at 110 °C for 12 h.

    Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 5-15% EtOAc/ pet ether) afforded a red oil. This was subjected to crystallization (DCM-pentane 1:3) to get pure 1c as an off-white crystalline solid (2.450 g, 10.0 mmol; 47% yield). Rf = 0.10 (10% EtOAc in pet ether);

    Melting point = 79 °C; FT-IR (KBr): ν 2920 (m), 1564 (s), 1558 (s), 1382 (s), 825 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.37 (d, J = 8.4 Hz; 2H), 7.17 (d, J = 8.4 Hz; 2H), 4.70-4.81 (m;

                                                                 (1) R. Ballini, G. Bosica, D. Fiorini and A. Palmieri, Synthesis, 2004, 1938.

    1c

    NO2

    NO2Cl

    Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2013

  • Singha Roy & Mukherjee, SI-Part-A, Page S-3  

    4H), 4.27-4.34 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 135.2, 132.5, 129.8, 128.7, 76.4, 41.1; HRMS (ESI+): Calculated for C9H9N2O4ClNa ([M + Na]+): 267.0149, found: 267.0151. 1-Bromo-2-(1,3-dinitropropan-2-yl)benzene (1d): Reaction was performed at 110 °C for 6 h.

    Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc in pet ether) afforded a red oil. This was subjected to solidification using DCM-pet ether mixture (1:3) to get pure 1d as an off-white solid (650 mg, 2.248 mmol; 28% yield). Rf = 0.30 (20% EtOAc in pet ether);

    Melting point = 45 °C; FT-IR (neat): ν 2926 (m), 1560 (s), 1551 (s), 1385(s), 1374 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.64 (dd, J = 1.3, 8.0 Hz; 1H), 7.33 (dt, J = 1.3, 7.6 Hz; 1H), 7.20-7.25 (m; 1H), 7.17-7.19 (m; 1H), 4.87-4.89 (m; 4H), 4.78-4.84 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 134.1, 133.2, 130.4, 128.4, 127.8, 124.3, 75.2, 40.5; HRMS (ESI+): Calculated for C9H9N2O4BrNa ([M + Na]+): 310.9643, found: 310.9646. 1-(1,3-Dinitropropan-2-yl)-2-fluorobenzene (1e): Reaction was performed at 110 °C for 8 h.

    Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc/pet ether) afforded 1e as a orange-yellow oil (1.186 g, 5.2 mmol; 42% yield). Rf = 0.40 (20% EtOAc in pet ether); FT-IR (neat): ν 2922 (m), 1557 (s), 1494 (m), 1433 (m), 1378 (s) cm−1; 1H-NMR (400 MHz, CDCl3):

    δ 7.31-7.37 (m; 1H), 7.20-7.25 (m; 1H), 7.08-7.16 (m; 2H), 4.77-4.87 (m; 4H), 4.46-4.53 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 160.6 (d, J = 247 Hz), 130.8 (d, J = 8 Hz), 129.8 (d, J = 4 Hz), 125.0 (d, J = 3 Hz), 121.1 (d, J = 13 Hz), 116.3 (d, J = 22 Hz), 75.1 (d, J = 3 Hz), 37.4. 2,4-Dichloro-1-(1,3-dinitropropan-2-yl)benzene (1f): Reaction was performed at 110 °C for 6

    h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc/pet ether) afforded a orange-yellow oil. This was subjected to solidification using a chloroform-pet ether mixture (1:3) to obtain 1f as an off-white solid (470 mg, 1.68 mmol; 20% yield). Rf = 0.30 (20%

    EtOAc in pet ether); Melting point = 95 °C; FT-IR (KBr): ν 2925 (m), 1571 (s), 1382 (s), 1102 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.49 (d, J = 2.1 Hz; 1H), 7.29 (dd, J = 2.1, 8.4 Hz; 1H), 7.15 (d, J = 8.4 Hz; 1H), 4.87-4.90 (m; 4H), 4.69-4.78 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 135.8, 134.5, 130.7, 130.1, 129.1, 128.2, 74.9, 38.1. 1-(1,3-Dinitropropan-2-yl)naphthalene (1h): Reaction was performed at 110 °C for 6 h.

    Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc/pet ether) afforded a red oil. This was subjected to solidification with EtOAc-toluene-pentane (3:3:4) mixture to obtain pure 1h as

    1d

    NO2

    NO2

    Br

    Electronic Supplementary Material (ESI) for Chemical Communications This journal is © The Royal Society of Chemistry 2013

  • Singha Roy & Mukherjee, SI-Part-A, Page S-4  

    an off-white amorphous solid (526 mg, 2.0 mmol; 20% yield). Rf = 0.55 (25% EtOAc in pet ether); Melting point = 86 °C; FT-IR (neat): ν 2924 (w), 1569 (s), 1550 (s), 1387 (m), 1372 (m), 805(m), 784 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 8.10-8.13 (m; 1H), 7.89-7.91 (m; 1H), 7.84-7.86 (m; 1H), 7.63-7.67 (m; 1H), 7.55-7.59 (m; 1H), 7.42-7.46 (m; 1H), 7.31-7.33 (m; 1H), 5.22-5.29 (m; 1H), 4.87-4.96 (m; 4H); 13C-NMR (100 MHz, CDCl3): δ 134.2, 130.6, 129.9, 129.7, 129.5, 127.6, 126.5, 125.2, 123.8, 121.5, 76.2, 36.2; HRMS (ESI+): Calculated for C13H12N2O4Na ([M + Na]+): 283.0695, found: 283.0697. 5-(1,3-Dinitropropan-2-yl)benzo[d][1,3]dioxole (1i): Reaction was performed at 110 °C for 5

    h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-25% EtOAc/pet ether) afforded a orange colored solid. It was re- crystallized from a DCM-pet ether mixture to obtain pure 1i as a white flaky solid (603 mg, 2.370 mmol; 35% yield). Rf = 0.20 (20% EtOAc in pet ether);

    Melting point = 89 °C; FT-IR (KBr): ν 2921 (m), 1560 (s), 1547 (s), 1443 (m), 1382 (s), 1257 (s), 1045 (m), 641 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 6.73-6.83 (m; 1H), 6.59-6.72 (m; 2H), 5.89-6.02 (m; 2H), 4.60-4.79 (m; 4H), 4.15-4.30 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 148.4, 148.1, 127.4, 120.9, 109.0, 107.4, 101.5, 76.8, 41.5; HRMS (ESI+): Calculated for C10H10N2O6Na ([M + Na]+): 277.0437, found: 277.0438. 2-(1,3-Dinitropropan-2-yl)furan (1j):