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Direct oxidation of Δ2-isoxazolines synthesis by metal ion-mediated diastereoface-selective 1,3-dipolar cycloaddition with “activated” DMSO
⁎Corresponding author. Tel.: +216 52557560. bh_naoufel@yahoo.fr (Naoufel Ben Hamadi)
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Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Peer review under responsibility of King Saud University.
Abstract
A series of 4-hydroxyl-Δ2-isoxazol-6(6aH)-one derivatives was prepared by magnesium ion-mediated diastereoface-selective 1,3-dipolar cycloaddition of aromatic nitrile oxides with pyrrolidinone derivatives. The reaction of 4-hydroxyl-Δ2-isoxazol-6(6aH)-one derivatives with dimethylsulfoxide and oxalyl chloride under Swern conditions led to a Δ2-isoxazole-4,6(5H,6aH)-dione.
Keywords
1,3-Dipolar cycloaddition
Δ2-Isoxazol-6(6aH)-one
Δ2-Isoxazole-4,6(5H,6aH)-dione
Stereoselectivity
Swern oxidation
1 Introduction
A large part of the research of stereocontrolled versions of 1,3-dipolar cycloaddition in the last few years dealt with the influence exerted by a stereocentre located in either of the two cycloaddends (Pelissier, 2007; Hiroyuki et al., 2009; Peng et al., 2008). With our efforts to utilize heterocyclic compounds as dipolarophile components in 1,3-dipolar cycloaddition reactions (Ben Hamadi and Msaddek, 2007; Ben Hamadi et al., 2012; Louhichi et al., 2012), we have recently demonstrated that nitrile oxides react with chiral alkene to produce mainly anti-adducts with >80% π-facial stereoselectivity (Ben Hamadi and Msaddek, 2011). Since Lewis acids are a powerful tool in organic synthesis, one of today’s challenges in the field of 1,3-dipolar reactions is the Lewis acid-induced control of regio- and steroselectivities in these reactions (Andrei and Peter, 2010). The Lewis acid-catalyzed reaction control of nitrile oxide cycloadditions must be an important research subject (Hidetoshi et al., 2000). Dimethylsulfoxide is widely employed as an oxidant, most notably in the transformation of primary alcohols into aldehydes (Tidwell, 1990). However, many of these methods are subjected to certain drawbacks such as longer reaction times, low yields and toxicity due to the presence of some elements embodied in the reagents utilized. So still there is a need for the development of new catalysts which can overcome all these drawbacks.
Therefore, we report in the present paper the investigation of reactions of chiral dipolarophiles and aromatic nitrile oxide to afforde the Δ2-isoxazole-4,6(5H,6aH)-dione. We show that a swern reaction of 4-hydroxyl-Δ2-isoxazol-6(6aH)-one pathway alternative to that is possible, involving the formation of Δ2-isoxazole-4,6(5H,6aH)-dione.
2 Results and discussion
The reaction of 5-hydroxy-3-methyl-N-phenyl-1,5-dihydropyrrol-2-one 1 with aromatic nitrile oxide 2 at 110 °C in toluene, without metal ions, gave a mixture of diastereomeric cycloaducts [3].
Lewis acids have been employed successfully as catalysts for 1,3-dipolar cycloaddition reaction between aromatic nitrile oxides and pyrrolidinone 1. Although the reactions also proceeded smoothly in the presence of a Lewis acid (0.5 equiv. to 1), diastereoselectivities of reactions were not improved. Increase in the amount of MgBr2 to 1 equiv. decreased the selectivity under similar conditions (Table 1). Examination of the electronic nature of benzonitrile oxides and pyrrolidinone 1 was carried out. As shown in Table 1 (Entry 6), the nitrile oxides having an electron-donating substituent showed higher diasteroselectivities.
The synthetic route to the targeted Δ2-isoxazolines 3ae–be is outlined in Scheme 1. In this paper, two synthetic approaches toward the Δ2-isoxazoline system have been reported. The first approach is based on the 1,3-dipolar cycloaddition of 5-hydroxy-4-methyl-1,5-dihydropyrrol-2-ones 1a–b with aromatic nitrile oxides 2c–e at 110 °C in toluene solution for 2 h, compound 3ae–be was obtained. The addition of aromatic nitrile oxydes 2 with 5-hydroxy-4-methyl-1,5-dihydropyrrol-2-ones as both a regio and diastereospecific reaction is described. (Scheme 1) The second reaction pathway as shown in Scheme 1, is the reaction between Δ2-isoxazoline derivatives 3ac–be and dimethylsulfoxide under Swern conditions which gave good yields of Δ2-isoxazoline derivatives 5ac–be (Konopikova et al. 1992).
3 Conclusion
In conclusion, we have developed a methodology for the magnesium ion-based stereocontrol of aromatic nitrile oxides with 5-hydroxy-4-methyl-1,5-dihydropyrrol-2-ones. The Swern conditions, involving the use of very simple and inexpensive reagents, allow the one-pot transformation of 4-hydroxyl-Δ2-isoxazol-6(6aH)-one with a Δ2-isoxazole-4,6(5H,6aH)-dione into synthetically valuable. These findings constitute a significant addition to the growing list of synthetic applications of activated dimethylsulfoxide.
4 Experimental details
4.1 General
Infrared spectra were recorded on a Perkin-Elmer IR-197 spectrophotometer in KBr disks. NMR spectra were obtained with a Bruker AC 300 spectrometer operating at 300 MHz for 1H and at 75.64 MHz for 13C using TMS as the internal standard. Elemental analysis was performed with a Perkin–Elmer 240B microanalyzer. The melting points, thermal transitions, and mesomorphic textures were determined using an Olympus BX50 microscope equipped with a Mettler Toledo FP-82 hot-stage and a PM-30 exposure control unit.
4.2 Materials
All the reagents were obtained from commercial sources and used without further purification. 5-Hydroxy-4-methyl-1,5-dihydropyrrol-2-ones 1a–b were obtained by the reduction of citraconimide derivatives with NaBH4 (Nobuyuki et al., 2002). The organic solvents were of commercial grade quality and all were dried by traditional methods. In general, all the compounds were purified by column chromatography on silica gel (60–120 mesh), and crystallization from analytical grade solvents. The purity of the sample was checked by thin-layer chromatography (Merck Kieselgel 60F254).
4.3 Addition of aromatic nitrile oxides to 5-hydroxy-1,5-dihydropyrrol-2-one derivatives
A solution of dipolarophiles 4a–b (1 mmol), MgBr2 (x mmol, see Table 1) and chloroximes 2c–e (1.1 mmol) in toluene (10 mL), was stirred at 110 °C. To this solution trimethylamine (0.2 mL), dissolved in toluene (10 mL), was added dropwise. The precipitated triethylammonium chloride was removed by filtration and the filtrate was concentrated in vacuo, and chromatography (SiO2; ethyl acetate/petroleum ether, 2:1) to afford compounds 5ac–be.
4.4 Oxidation of isoxazolines 5ac-be
To a solution of oxalyl chloride (5 equiv) in dry CH2Cl2 (10 mL), at −78 °C under an argon atmosphere, was added DMSO (7 equiv). The solution was stirred for 10 min, until effervescence ceased. A solution of the isoxazolines 3ac–be (1 mmol) in dry CH2Cl2 (5 mL) was added dropwise, and the solution was stirred for 10 min at −78 °C. Triethylamine (10 equiv) was then added and the solution was left to warm to 0 °C for 30 min, while stirring. The reaction mixture was diluted with CH2Cl2 (20 mL) and washed with saturated aqueous NH4Cl (3 × 20 mL). The organic layer was dried (MgSO4) and evaporated, and the residue was purified by chromatography (SiO2; ethyl acetate/petroleum ether, 1:4) to afford compounds 5ac–be.
4.4.1 6a-methyl-3,5-diphenyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-4,6-dione 5ac
Yield (0.244 g, 80%), white solid. M.p = 197–199 °C. Anal. Calcd. For C18H14N2O3: C, 70.57; H, 4.61; N, 9.15%; Found: C, 70.46; H, 4.56; N, 9.00%; IR (KBr) νcm−1: 1635 (C⚌N). 1H NMR (CDCl3; 300 MHz) δ: 1.89 (s, 3H, CH3), 4.62 (s, 1H, 3a-H), 7.30–8.05 (m, 10H, Harom). 13C{1H}NMR (CDCl3; 75.47 MHz) δ: 19.59 (CH3), 59.85 (C-3a), 88.33 (C-6a), 126.57–131.49 (Carom), 153.08 (C-3), 169.87 (C-4), 173.21 (C-6).
4.4.2 6a-methyl-3-(4-methylphenyl)-5-phenyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-4,6-dione 5ad
Yield (0.304 g, 95%), white solid. M.p = 155–157 °C. Anal. Calcd. For C19H16N2O3: C, 71.23; H, 5.04; N, 8.75%; Found: C, 71.12; H, 4.91; N, 8.50%. IR (KBr) νcm−1: 1638 (C⚌N). 1H NMR (CDCl3; 300 MHz) δ: 1.76 (s, 3H, CH3), 2.31 (s, 3H, CH3), 4.49 (s, 1H, 3a-H), 7.16–7.82 (m, 9H, Harom). 13C{1H}NMR (CDCl3; 75.47 MHz) δ: 19.54 (CH3), 21.93 (CH3), 59.97 (C-3a), 88.13 (C-6a), 124.80–141.93 (Carom), 153.07 (C-3), 169.94 (C-4), 173.33 (C-6).
4.4.3 3-(4-methoxyphenyl)-6a-methyl-5-phenyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-4,6-dione 5ae
Yield (0.285 g, 85%), white solid. M.p = 222–224 °C. Anal. Calcd. For C19H16N2O4: C, 67.84; H, 4.80; N, 8.33%; Found C, 67.69; H, 4.90; N, 8.30%. IR (KBr) νcm−1: 1640 (C⚌N). 1H NMR (DMSO; 300 MHz) δ: 1.75 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 5.16 (s, 1H, 3a-H), 7.05 (d, 2H) and 7.89 (d, 2H): AA'BB' part. J = 8.7 Hz, 7.30–7.53 (m, 5H, Harom). 13C{1H}NMR (DMSO; 75.47 MHz) δ: 18.49 (CH3), 55.73 (OCH3), 59.30 (C-3a), 88.32 (C-6a), 114.51–161.52 (Carom), 153.28 (C-3), 170.72 (C-4), 173.68 (C-6).
4.4.4 5-(4-methoxyphenyl)-6a-methyl-3-phenyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-4,6-dione 5bc
Yield (0.269 g, 80%), white solid. M.p = 153–155 °C Anal. Calcd. For C19H16N2O4: C, 67.84; H, 4.80; N, 8.33%; Found: C, 67.80; H, 4.75; N, 8.20%. IR (KBr) νcm−1: 1634 (C⚌N). RMN 1H (CDCl3; 300 MHz) δ: 1.85 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 4.58 (s, 1H, 3a-H), 6.99; 7.21 (AA'BB', Harom, JAA'BB' = 8.7 Hz), 7.46–8.02 (m, 5H, Harom). 13C{1H}NMR (CDCl3; 75,47 MHz) δ: 19.24 (CH3), 55.58 (OCH3), 59.41 (C-3a), 87.95 (C-6a), 114.55–159.85 (Carom), 152.77 (C-3), 169.77 (C-4), 173.10 (C-6).
4.4.5 5-(4-methoxyphenyl)-6a-methyl-3-(4-methylphenyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-4,6-dione 5bd
Yield (0.315 g, 90%), white solid. M.p = 166 °C. Anal. Calcd. For C20H18N2O4: C, 68,55; H, 5,19; N, 8,00%; Found: C, 68,40; H, 5,10; N, 8,10%. IR (KBr) νcm−1: 1633 (C⚌N). 1H NMR (CDCl3; 300 MHz) δ: 1,84 (s, 3H, CH3), 2,29 (s, 3H, CH3), 3,78 (s, 3H, OCH3), 4,59 (s, 1H, 3a-H), 6,99–7,85 (m, 8H, Harom). 13C{1H}NMR (CDCl3; 75,47 MHz) δ: 19,20 (CH3), 22,04 (CH3), 55,60 (OCH3), 59,36 (C-3a), 87,89 (C-6a), 118,01–159,65 (Carom), 151,97 (C-3), 168,90 (C-4), 173,15 (C-6).
4.4.6 3,5-di(4-methoxyphényl)-6a-methyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-4,6-dione 5be
Yield (0.347 g, 95%), white solid. M.p = 198–200 °C. Anal. Calcd. For: C, 65.56; H, 4.96; N, 7.64%; Found: C, 65.40; H, 4.85; N, 7.70%. IR (KBr) νcm−1: 1640 (C⚌N). 1H NMR (DMSO; 300 MHz) δ: 1.87 (s, 3H, CH3), 3.83 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 4.54 (s, 1H, 3a-H), 6.93 (d, 2H) and 7.18 (d, 2H): AA'BB' part. J = 9 Hz, 7.05 (d, 2H) and 7.08 (d, 2H): AA'BB' part. J = 9 Hz. 13C{1H}NMR (DMSO; 75,47 MHz) δ: 19.61 (CH3), 55.81 (OCH3), 55.91 (OCH3), 60.10 (C-3a), 87.91 (C-6a), 114.64–162.15 (Carom), 152.60 (C-3), 170.27 (C-4), 173.57 (C-6).
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