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Synlett 2018; 29(10): 1307-1313
DOI: 10.1055/s-0036-1591841
letter
© Georg Thieme Verlag Stuttgart · New York

Activation of Michael Acceptors by Halogen-Bond Donors

Daniel von der Heiden
Department für Chemie, Universität zu Köln, Greinstraße 4, 50939 Köln, Germany   eMail: mbreugst@uni-koeln.de
,
Eric Detmar
Department für Chemie, Universität zu Köln, Greinstraße 4, 50939 Köln, Germany   eMail: mbreugst@uni-koeln.de
,
Robert Kuchta
Department für Chemie, Universität zu Köln, Greinstraße 4, 50939 Köln, Germany   eMail: mbreugst@uni-koeln.de
,
Martin Breugst  *
Department für Chemie, Universität zu Köln, Greinstraße 4, 50939 Köln, Germany   eMail: mbreugst@uni-koeln.de
› Institutsangaben
Financial support from the Fonds der Chemischen Industrie (Liebig scholarship to M.B. and Ph.D. scholarships to D.v.d.H.) is gratefully acknowledged.
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Publikationsverlauf

Received: 08. September 2017

Accepted after revision: 03. November 2017

Publikationsdatum:
01. Dezember 2017 (online)

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Published as part of the Special Section 9th EuCheMS Organic Division Young Investigator Workshop

In memoriam Professor J. Peter Guthrie

Abstract

Extending earlier studies on iodine catalysis, experimental investigations show that various halogen-bond donors can also be employed to accelerate the Michael addition between trans-crotonophenone and indole. Solvent as well as counteranion effects have been analyzed, and kinetic and computational investigations provide additional insights into the mode of activation.

Key words

catalysis - DFT calculations - halogen bonding - kinetics - solvent effects

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591841.
  • Supporting Information
 

  • References and Notes

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  • 12 C1–OTf was synthesized from 2-iodo-1-octlybenzimidazole (1.0 equiv) and methyl triflate (1.2 equiv) as described in the Supporting Information. 1H NMR (CDCl3, 300 MHz): δ = 0.86 (t, 3 J HH = 6.3 Hz, 3 H), 1.26–1.43 (m, 10 H), 1.90 (quint, 3 J HH = 7.5 Hz, 2 H), 4.16 (s, 3 H), 4.49 (t, 3 J HH = 7.6 Hz, 2 H), 7.56–7.63(m, 2 H), 7.70–7.75 (m, 1 H), 7.82–7.87 (m, 1 H). 13C{apt} NMR (CDCl3, 75 MHz): δ = 14.1 (s), 22.6 (s), 26.7 (s), 29.1 (s), 29.2 (s), 29.3 (s), 31.7 (s), 36.9 (s), 50.6 (s), 112.0 (s), 112.7 (s), 13.4 (s), 120.6 (d, 1 J CF = 320.4 Hz), 127.3 (s), 127.4 (s), 133.2 (s), 134.2 (s). IR (neat, ATR): ṽ = 2928 (w), 2857 (w), 1479 (w), 1028 (s), 747 (m), 637 (s) cm–1. ESI-HRMS: m/z [M]+ calcd for C16H24N2I+: 371.0979; found: 371.0976. Anal. Calcd for C17H24F3IN2O3S: C, 39.24; H, 4.65; N, 5.38. Found: C, 39.31; H, 4.91; N, 5.16.C5–OTf was obtained from 2-iodo-3-methyl-1-octylimidazolium bromide (1.0 equiv) by anion metathesis with NaOTf (1.5 equiv) in CH2Cl2/H2O. 1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, 3 J HH = 6.8 Hz, 3 H), 1.23–1.39 (m, 10 H), 1.84 (quint, 3 J HH = 7.2 Hz), 3.95 (s, 3 H), 4.17 (t, 3 J HH = 7.5 Hz, 2 H), 7.57 (d, 3 J HH = 2.0 Hz, 1 H), 7.73 (d, 3 J HH = 2.0 Hz, 1 H). 13C{apt} NMR (CDCl3, 125 MHz): δ = 14.2 (s), 22.7 (s), 26.4 (s), 29.1 (s), 29.1 (s), 31.8 (s), 30.5 (s), 39.9 (s), 53.1 (s), 103.1 (s), 120.8 (q, 1 J CF = 320 Hz), 124.9 (s), 126.7 (s). 19F{1H} NMR (CDCl3, 376 MHz) δ = –78.2 (s), –78.4 (d, 1 J F13C = 320 MHz). IR (neat, ATR): ṽ = 3107 (w), 2926 (w), 2857 (w), 1568 (w), 1497 (w), 1456 (w), 1246 (s), 1223 (m), 1153 (s), 1028 (s), 756 (w), 665 (w), 637 (s) cm–1. ESI-LRMS: m/z (%) = 321.0 (100) [C5]+ 320.8 (20) [Na(OTf)2]–, 148.9 (100) [OTf]–. ESI-HRMS [C5]+: m/z calcd for C12H22N2I+: 321.0822; found: 321.0821.
  • 13 Typical Experimental ProcedureA stock solution (1.00 mL) containing the reactants 1 and 2 as well as the internal standard SiEt4 was added to the pure catalyst in an NMR tube. This resulted in approximate concentration of 50 mM in the catalyst, 500 mM in the reactants, and 125 mM in the standard. The course of the reaction was followed by 1H NMR spectroscopy. If a reasonable amount of product was observed in the final NMR spectrum, the reaction was deactivated with 100 μL DMSO. Within 2 h, all volatile residues were removed under reduced pressure, and the product was isolated by column chromatography (SiO2, cyclohexane/EtOAc = 9:1 (v/v), Rf = 0.11) as an off-white solid.Analytical Data for Compound 3103–104 °C. 1H NMR (CD2Cl2, 300 MHz): δ = 1.42 (d, 3 J = 6.9 Hz), 3.23 (dd, 3 J = 8.5 Hz, 2 J = 16.5 Hz, 1 H), 3.44 (dd, 3 J = 5.4 Hz, 2 J = 16.4 Hz, 1 H), 3.73–3.84 (m, 1 H), 6.97 (d, 3 J = 2.2 Hz, 1 H), 7.04–7.16 (m, 2 H), 7.31 (d, 3 J = 8.0 Hz, 1 H), 7.41 (t, 3 J = 7.5 Hz, 2 H), 7.52 (t, 3 J = 7.4 Hz 1 H), 7.63 (d, 3 J = 7.8 Hz, 1 H), 7.91–7.93 (m, 2 H), 8.12 (br s, 1 H). 13C{1H} NMR (CD2Cl2, 75.5 MHz): δ = 21.4 (s), 27.5 (s), 46.8 (s), 111.7 (s), 119.5 (s), 119.5 (s), 120.7 (s), 121.7 (s), 122.2 (s), 126.8 (s), 128.4 (s), 128.9 (s), 133.3 (s), 137.0 (s), 137.8 (s), 200.0 (s). IR (neat, ATR): ṽ = 3352 (m), 3057 (w), 2982 (w), 2961 (w), 2872 (w), 1667 (s), 1618 (w), 1593 (w), 1489 (w), 1445 (m), 1339 (m) 1215 (s), 999 (m), 745 (s), 60 (m) cm–1. ESI-HRMS: m/z [M + H]+ calcd for C18H18NO+: 264.1383; found: 264.1384.
  • 14 Slightly higher values (up to 10 %) could be detected for CDCl3 and CH2Cl2.
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  • 20 Optimizations were performed with M06-2X-D3/6-311+G(d,p) in the gas phase and solution (iefpcm for benzene and methanol). Electronic energies were calculated with M06-2X-D3/aug-cc-pVTZ either in the gas phase or in solution. The aug-cc-pVTZ-PP pseudopotential was used for iodine. See the Supporting Information for details.