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Synlett 2018; 29(10): 1307-1313
DOI: 10.1055/s-0036-1591841
DOI: 10.1055/s-0036-1591841
letter
Activation of Michael Acceptors by Halogen-Bond Donors
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.Further Information
Publication History
Received: 08 September 2017
Accepted after revision: 03 November 2017
Publication Date:
01 December 2017 (online)
![](https://www.thieme-connect.de/media/synlett/201810/lookinside/thumbnails/st-2017-b0676-l_10-1055_s-0036-1591841-1.jpg)
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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591841.
- Supporting Information
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References and Notes
- 1a Halogen Bonding I . Metrangolo P. Resnati G. Springer; Heidelberg: 2015
- 1b Halogen Bonding II . Metrangolo P. Resnati G. Springer; Heidelberg: 2015
- 1c Cavallo G. Metrangolo P. Milani R. Pilati T. Priimagi A. Resnati G. Terraneo G. Chem. Rev. 2016; 116: 2478
- 2 Bruckmann A. Pena MA. Bolm C. Synlett 2008; 900
- 3a Bulfield D. Huber SM. Chem. Eur. J. 2016; 22: 14434
- 3b Breugst M. von der Heiden D. Schmauck J. Synthesis 2017; 49: 3224
- 3c Walter SM. Kniep F. Herdtweck E. Huber SM. Angew. Chem. Int. Ed. 2011; 50: 7187
- 3d Kniep F. Rout L. Walter SM. Bensch HK. V. Jungbauer SH. Herdtweck E. Huber SM. Chem. Commun. 2012; 48: 9299
- 3e Kniep F. Jungbauer SH. Zhang Q. Walter SM. Schindler S. Schnapperelle I. Herdtweck E. Huber SM. Angew. Chem. Int. Ed. 2013; 52: 7028
- 3f Castelli R. Schindler S. Walter SM. Kniep F. Overkleeft HS. Van der Marel GA. Huber SM. Codée JD. C. Chem. Asian J. 2014; 9: 2095
- 3g Jungbauer SH. Huber SM. J. Am. Chem. Soc. 2015; 137: 12110
- 4a Takeda Y. Hisakuni D. Lin C.-H. Minakata S. Org. Lett. 2015; 17: 318
- 4b He W. Ge Y.-C. Tan C.-H. Org. Lett. 2014; 16: 3244
- 5 Jungbauer SH. Walter SM. Schindler S. Rout L. Kniep F. Huber SM. Chem. Commun. 2014; 50: 6281
- 6 Saito M. Kobayashi Y. Tsuzuki S. Takemoto Y. Angew. Chem. Int. Ed. 2017; 56: 7653
- 7a Webb JA. Klijn JE. Hill PA. Bennett JL. Goroff NS. J. Org. Chem. 2004; 69: 660
- 7b Goroff NS. Curtis SM. Webb JA. Fowler FW. Lauher JW. Org. Lett. 2005; 7: 1891
- 7c Lieffrig J. Jeannin O. Fourmigué M. J. Am. Chem. Soc. 2013; 135: 6200
- 7d Dumele O. Wu D. Trapp N. Goroff N. Diederich F. Org. Lett. 2014; 16: 4722
- 8 Matsuzawa A. Takeuchi S. Sugita K. Chem. Asian J. 2016; 11: 2863
- 9a Breugst M. Detmar E. von der Heiden D. ACS Catal. 2016; 6: 3203
- 9b von der Heiden D. Bozkus S. Klussmann M. Breugst M. J. Org. Chem. 2017; 82: 4037
- 10 The concept of hidden Brønsted acid catalysis was originally introduced by Hintermann: Dang TT. Boeck F. Hintermann F. J. Org. Chem. 2011; 76: 9353
- 11 Togo H. Iida S. Synlett 2006; 2159
- 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.
- 15a Klæboe P. Acta Chem. Scand. 1964; 18: 27
- 15b Laurence C. Gal J.-F. Lewis Basicity and Affinity Scales: Data and Measurement . John Wiley and Sons; Chichester: 2010
- 15c Laurence C. Graton J. Berthelot M. El Ghomari MJ. Chem. Eur. J. 2011; 17: 10431
- 16 Walter SM. Jungbauer SH. Kniep F. Schindler S. Herdtweck E. Huber SM. J. Fluorine Chem. 2013; 150: 14
- 17a Farnham WB. Dixon DA. Calabrese JC. J. Am. Chem. Soc. 1988; 110: 8453
- 17b Kuhn N. Abu-Rayyan A. Steimann MZ. Anorg. Allg. Chem. 2003; 629: 2066
- 17c Jungbauer SH. Schindler S. Herdtweck E. Keller S. Huber SM. Chem. Eur. J. 2015; 21: 13625
- 18a Rothenberg G. Catalysis: Concepts and Green Applications . Wiley-VCH; Weinheim: 2008
- 18b Nam E. Alokolaro PE. Swartz RD. Gleaves MC. Pikul J. Kovacs JA. Inorg. Chem. 2011; 50: 1592
- 19 For an excellent review on weakly and noncoordinating anions and their reactivties, see: Krossing I. Raabe I. Angew. Chem. Int. Ed. 2004; 43: 2066
- 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.
- 21a Sarwar MG. Dragisic B. Salsberg LJ. Gouliaras C. Taylor MS. J. Am. Chem. Soc. 2010; 132: 1646
- 21b Walter SM. Kniep F. Rout L. Schmidtchen FP. Herdtweck E. Huber SM. J. Am. Chem. Soc. 2012; 134: 8507
- 21c Robertson CC. Perutz RN. Brammer L. Hunter CA. Chem. Sci. 2014; 5: 4179
- 21d Robertson CC. Wright JS. Carrington EJ. Perutz RN. Hunter CA. Brammer L. Chem. Sci. 2017; 8: 5392
For selected reviews, see:
For selected examples, see: