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DOI: 10.1055/s-0034-1378723
Asymmetric Michael Addition of Malonates to Enones Catalyzed by an α-d-Glucopyranoside-Based Crown Ether
Publication History
Received: 04 March 2015
Accepted after revision: 07 May 2015
Publication Date:
24 June 2015 (online)
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Abstract
The chiral monoaza-15-crown-5 lariat ether annelated to methyl-4,6-O-benzylidene-α-d-glucopyranoside has been applied as a phase-transfer catalyst in several Michael addition reactions under mild conditions affording the adducts with good to excellent enantioselectivities. In the addition of α-substituted diethyl malonates to trans-chalcones, the substituents of the reactants had a significant impact on the yield and enantioselectivity. Among the reactions of substituted diethyl malonates, that of diethyl-2-acetoxymalonate gave the best results (up to 97% ee). New phase-transfer-catalyzed cyclopropanation reactions (MIRC reactions) of a few enones were also developed using diethyl 2-bromomalonate as the nucleophile. The corresponding chiral cyclopropane derivatives were formed with enantioselectivities up to 92% from 2-benzylidenemalononitrile starting materials, in up to 60% enantiomeric excess using 2-benzylidene-1,3-diphenyl-1,3-propanediones, and in up to 88% optical purity applying trans-chalcones as the starting materials.
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References and Notes
- 1a Noyori R. Asymmetric Catalysis in Organic Synthesis . John Wiley and Sons; New York: 1994
- 1b Krause N, Hoffman-Röder A. Synthesis 2001; 171
- 1c Dalko PI In Comprehensive Enantioselective Organocatalysis . Vol. 1. Dalko PI. Wiley-VCH; Weinheim: 2013: 119-160
- 1d O’Donnell MI In Catalytic Asymmetric Synthesis, 2nd ed. Ojima I. Wiley-VCH; New York: 2000: 231-280
- 1e Berkessel A, Gröger H. Asymmetric Organocatalysis . Wiley-VCH; Weinheim: 2005: 45-82
- 2a Maruoka K, Ooi T. Chem. Rev. 2003; 103: 3013
- 2b O’Donnell MJ. Acc. Chem. Res. 2004; 37: 506
- 2c Lygo B, Andrews BI. Acc. Chem. Res. 2004; 37: 518
- 2d Vachon J, Lacour J. Chimia 2006; 60: 266
- 2e Hashimoto T, Maruoka K. Chem. Rev. 2007; 107: 5656
- 2f Ooi T, Maruoka K. Angew. Chem. Int. Ed. 2007; 46: 4222
- 2g Maruoka K. Org. Process Res. Dev. 2008; 12: 679
- 2h Marouka K. Asymmetric Phase Transfer Catalysis . Wiley-VCH; Weinheim: 2008
- 2i Maruoka K, Shirakawa S. Angew. Chem. Int. Ed. 2013; 52: 4312
- 3 Bakó P, Czinege E, Bakó T, Czugler M, Tőke L. Tetrahedron: Asymmetry 1999; 10: 4539
- 4a Jarosz S, Listkowski A. Curr. Org. Chem. 2006; 10: 643
- 4b Itoh T, Shirakami S. Heterocycles 2001; 55: 37
- 4c Bakó P, Keglevich G, Rapi Z. Lett. Org. Chem. 2010; 7: 645
- 5a Kim YS, Matsunaga S, Das J, Sekine A, Ohshima T, Shibasaki M. J. Am. Chem. Soc. 2000; 122: 6506
- 5b Matsunaga S, Ohshima T, Shibasaki M. Tetrahedron Lett. 2000; 41: 8473
- 6 Hanessian S, Pham V. Org. Lett. 2000; 2: 2975
- 7a Narasimhan S, Balakumar VR, Radhakrishnan V. Tetrahedron Lett. 2001; 42: 719
- 7b Sundararajan G, Prabagaran N. Org. Lett. 2001; 3: 389
- 8 Perrard T, Plaquevent L.-C, Desmurs J.-R, Hebrault D. Org. Lett. 2000; 2: 2959
- 9a Ooi T, Ohara D, Fukumoto K, Maruoka K. Org. Lett. 2005; 7: 3195
- 9b Dere RT, Pal RR, Patil PS, Salunkhe MM. Tetrahedron Lett. 2003; 44: 5351
- 9c Akiyama T, Hara M, Fuchibe K, Sakamoto S, Yamaguchi K. Chem. Commun. 2003; 1734
- 10a Wang J, Li H, Zu L, Jiang W, Xie H, Duan W, Wang W. J. Am. Chem. Soc. 2006; 128: 12652
- 10b Jayaraman S, Kumaraguru D, Arockiam JB, Paulpandian S, Rajendiran B, Siva A. Synlett 2014; 25: 1685
- 11a General Procedure for the Michael Additions Unsaturated compound (1 mmol), substituted malonate (1.5 mmol), and the crown ether (0.15 mmol) were dissolved in a mixture of anhydrous THF (0.6 mL) and Et2O (2.4 mL) and dry Na2CO3 (2 mmol) was added. The reaction mixture was stirred at r.t. After completion of the reaction, the organic phase was concentrated in vacuo, and the residue was taken up in CH2Cl2 (10 mL), washed with cold 10% HCl (3 × 10 mL), then with H2O (10 mL), dried (Na2CO3 and Na2SO4), and concentrated. The crude product was purified by preparative TLC using silica gel and hexane–EtOAc (5:1) as the eluent. The enantioselectivities were determined by chiral HPLC analysis using a Chiralpack AD-H column, (20 °C, 256 nm, hexane–i-PrOH = 90:10, 0.8 mL/min) in comparison with authentic racemic materials.
- 11b Compound 5a: yield 72%; [α]D 22 + 9.4 (c 1, CHCl3); ee 96%; t r (major enantiomer) = 9.9 min, t r (minor enantiomer) = 13.2 min. 1H NMR (500 MHz, CDCl3): δ = 7.90 (d, J = 7.5 Hz, 2 H, ArH), 7.53 (t, J = 7.5 Hz, 1 H, ArH), 7.43 (t, J = 7.5 Hz, 2 H, ArH), 7.35 (d, J = 7.5 Hz, 2 H, ArH), 7.26–7.20 (m, 3 H, ArH), 4.37 (dd, J = 8.5, 4.0 Hz, 1 H, PhH), 4.24–4.16 (m, 2 H, OCH2), 4.02–3.89 (m, 2 H, OCH2), 3.67 (dd, J = 16.0, 4.0 Hz, 1 H, COCH2), 3.59 (dd, J = 17.5, 8.5 Hz, 1 H, COCH2), 2.23 (s, 3 H, COCH3), 1.23 (t, J = 7.0 Hz, 3 H, CH2CH 3), 1.06 (t, J = 7.0 Hz, 3 H, CH2CH 3) ppm. HRMS: m/z calcd for C24H26O7: 426.1679; found: 426.1680.
- 11c Compound 5j: yield 73%; [α]D 22 + 13.8 (c 1, CHCl3); ee 97%; t r (major enantiomer) = 24.9 min, t r (minor enantiomer) = 22.8 min. 1H NMR (500 MHz, CDCl3): δ = 7.89 (dd, J = 7.5, 1.0 Hz, 2 H, ArH), 7.53 (t, J = 7.5 Hz, 1 H, ArH), 7.43 (t, J = 7.5 Hz, 2 H, ArH), 7.26 (d, J = 8.5 Hz, 2 H, ArH), 6.77 (d, J = 8.5 Hz, 2 H, ArH), 4.31 (dd, J = 8.5, 4.0 Hz, 1 H, ArCH), 4.24–4.15 (m, 2 H, OCH2), 4.06–3.92 (m, 2 H, OCH2), 3.75 (s, 3 H, ArOCH3), 3.71 (dd, J = 18.0, 4.0 Hz, 1 H, COCH2), 3.56 (dd, J = 18.0, 9.0 Hz, 1 H, COCH2), 2.23 (s, 3 H, COCH3), 1.23 (t, J = 7.0 Hz, 3 H, CH2CH 3), 1.10 (t, J = 7.0 Hz, 3 H, CH2CH 3) ppm. HRMS: m/z calcd for C25H28O8: 456.1784; found: 456.1785.
- 12 Mako A, Rapi Z, Drahos L, Szollősy A, Keglevich G, Bako P. Lett. Org. Chem. 2010; 7: 424
-
13a Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
-
13b Gaunt MJ, Johansson CC. C. Chem. Rev. 2007; 107: 5596
- 13c Simone FD, Waser J. Synthesis 2009; 3353
-
13d Lindsay VN. G, Nicolas C, Charette AB. J. Am. Chem. Soc. 2011; 133: 8972
- 13e Falkowski JM, Liu S, Wang C, Lin W. Chem. Commun. 2012; 48: 6508
- 13f Benfatti F, de Nanteuil F, Waser J. Chem. Eur. J. 2012; 18: 4844
- 13g Benfatti F, de Nanteuil F, Waser J. Org. Lett. 2012; 14: 386
- 13h Liu JW. X, Dong S, Lin L, Feng X. J. Org. Chem. 2013; 78: 6322
- 13i Sun Y, Yang G, Shen Y, Hua Z, Chai Z. Tetrahedron 2013; 69: 2733
- 14a Arai S, Nakayama K, Ishida T, Shioiri T. Tetrahedron Lett. 1999; 40: 4215
- 14b Herchl R, Waser M. Tetrahedron 2014; 70: 1935
- 14c Fiandra CD, Piras L, Fini F, Disetti P, Moccia M, Adamo MF. A. Chem. Commun. 2012; 48: 3863
- 15 Herchl R, Waser M. Tetrahedron Lett. 2013; 54: 2472
- 16a Makosza M, Kwast A. Tetrahedron 1991; 41: 5001
- 16b Sun Y, Yang G, Shen Y, Hua Z, Chai Z. Tetrahedron 2013; 69: 2733
- 17a Compound 7a: yield 28%; [α]D 22 +17.5 (c 1, CHCl3); ee 88%; t r (major enantiomer) = 5.0 min, t r (minor enantiomer) = 9.3 min. 1H NMR (500 MHz, CDCl3): δ = 8.11 (d, J = 7.5 Hz, 2 H, ArH), 7.62 (t, J = 7.5 Hz, 1 H, ArH), 7.51 (t, J = 7.5 Hz, 2 H, ArH), 7.33–7.26 (m, 5 H, ArH), 4.14 (q, J = 7.0 Hz, 2 H, OCH2), 4.12 (d, J = 7.5 Hz, 1 H, COCH), 4.00 (q, J = 7.0 Hz, 2 H, OCH2), 3.89 (d, J = 7.5 Hz, 1 H, PhCH), 1.11 (t, J = 7.0 Hz, 3 H, CH3), 0.99 (t, J = 7.0 Hz, 3 H, CH3) ppm. HRMS: m/z calcd for C22H22O5: 366.1467; found: 366.1470.
- 17b Compound 9d: yield 74%; [α]D 22 –17.3 (c 1, CHCl3); ee 92%; t r (major enantiomer) = 4.3 min, t r (minor enantiomer) = 5.0 min. 1H NMR (500 MHz, CDCl3): δ = 7.25 (d, J = 8.0 Hz, 2 H, ArH), 7.20 (d, J = 8.0 Hz, 2 H, ArH), 4.42 (q, J = 7.0 Hz, 2 H, OCH2), 4.30–4.20 (m, 2 H, OCH2), 3.92 (s, 1 H, ArCH), 2.35 (s, 3 H, ArCH3), 1.38 (t, J = 7.0 Hz, 3 H), 1.21 (t, J = 7.0 Hz, 3 H) ppm. HRMS: m/z calcd for C18H18N2O4: 326.1267; found: 326.1270.
- 17c Compound 11a: yield 52%; [α]D 22 +68.9 (c 1, CHCl3); ee 60%; t r (major enantiomer) = 11.9 min, t r (minor enantiomer) = 41.1 min. 1H NMR (500 MHz, CDCl3): δ = 7.53 (d, J = 7.5 Hz, 2 H, ArH), 7.44 (d, J = 7.5 Hz, 2 H, ArH), 7.33 (d, J = 7.0 Hz, 2 H, ArH), 7.26–7.19 (m, 5 H, ArH), 7.14 (t, J = 7.5 Hz, 2 H, ArH), 7.10 (t, J = 7.5 Hz, 2 H, ArH), 5.64 (s, 1 H, PhCH), 4.47–4.40 (m, 1 H, OCH2), 4.38–4.29 (m, 1 H, OCH2), 3.87–3.80 (m, 1 H, OCH2), 3.64–3.57 (m, 1 H, OCH2), 1.35 (t, J = 7.0 Hz, 3 H, CH3), 0.84 (t, J = 7.0 Hz, 3 H, CH3). HRMS: m/z calcd for C29H26O6: 470.1729; found: 470.1733.
For selected examples on asymmetric cyclopropanation, see:
The corresponding coupling constants of 7.5 Hz (δ = 4.12 ppm, J = 7.5 Hz and δ = 3.89 ppm, J = 7.5 Hz) observed for the trans isomer are in agreement with the literature data. The corresponding constants would be J = 9.9 Hz in both cases for the cis compound. See: