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Synlett 2015; 26(13): 1847-1851
DOI: 10.1055/s-0034-1378723
letter
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Michael Addition of Malonates to Enones Catalyzed by an α-d-Glucopyranoside-Based Crown Ether

Péter Bakó*
a   Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521 Budapest, Hungary   Email: pbako@mail.bme.hu
,
Zsolt Rapi
a   Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521 Budapest, Hungary   Email: pbako@mail.bme.hu
,
Alajos Grün
a   Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521 Budapest, Hungary   Email: pbako@mail.bme.hu
,
Tamás Nemcsok
a   Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521 Budapest, Hungary   Email: pbako@mail.bme.hu
,
László Hegedűs
b   MTA-BME Organic Chemical Technology Research Group, Hungarian Academy of Sciences, Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 8, 1111 Budapest, Hungary
,
György Keglevich
a   Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521 Budapest, Hungary   Email: pbako@mail.bme.hu
› Author Affiliations
Further Information

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.

Key words

phase-transfer catalysis - sugar-based crown ethers - asymmetric Michael reactions - asymmetric cyclopropanations - enantioselectivity
 

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    • 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.