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Synlett 2014; 25(3): 349-354
DOI: 10.1055/s-0033-1340311
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© Georg Thieme Verlag Stuttgart · New York

Chiral Bis(oxazolidine)pyridine–Copper-Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles with Nitroalkenes

Toru Sato
Department of Chemistry, Graduate School of Science, Chiba University, Inage 263-8522, Japan   Fax: +81(43)2902889   Email: tarai@faculty.chiba-u.jp
,
Takayoshi Arai*
Department of Chemistry, Graduate School of Science, Chiba University, Inage 263-8522, Japan   Fax: +81(43)2902889   Email: tarai@faculty.chiba-u.jp
› Author Affiliations
Further Information

Publication History

Received: 21 October 2013

Accepted after revision: 31 October 2013

Publication Date:
06 December 2013 (online)

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Abstract

Catalytic asymmetric Friedel–Crafts reaction of indoles with nitroalkenes was catalyzed by the stereochemically tunable bis(oxazolidine)pyridine (PyBodine)–Cu(OTf)2 complex. Using the PyBodine(Val)–Cu(OTf)2 catalyst gave the Friedel–Crafts ­adducts with highly enantioselective manner. For the 1,4-bis[(E)-2-nitrovinyl]benzene, the reaction proceeded in a meso-trick manner to give the chiral double Friedel–Crafts adduct with 97% enantiomeric excess.

Key words

oxazolidine - copper - Friedel–Crafts alkylation - indole - nitroalkene - meso trick

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    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 19 General Procedure of the Synthesis of PyBodine To a solution of 2,6-pyridine dicarboxyaldehyde (0.5 mmol) in CH2Cl2 (2 mL) was added amino alcohol (1 mmol), and the mixture was stirred at r.t. for 6 h. The resulting solution was concentrated in vacuo to afford PyBodines. Analytical Data of PyBodine(Val) (L3) 1H NMR (400 MHz, DMSO-d 6): δ = 8.06 (t, J = 7.6 Hz, 1 H), 7.76 (d, J = 7.6 Hz, 2 H), 7.44–7.36 (m, 8 H), 7.31–7.28 (m, 2 H), 7.23–7.19 (m, 4 H), 7.13–7.11 (m, 6 H), 5.54 (d, J = 12.5 Hz, 2 H), 3.89 (dd, J = 12.5, 3.4 Hz, 2 H), 3.75 (t, J = 12.5 Hz, 2 H), 1.92–1.85 (m, 2 H), 1.08 (d, J = 6.7 Hz, 6 H), 0.15 (d, J = 6.7 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 155.0, 146.4, 143.8, 138.1, 128.1, 127.8, 127.6, 127.5, 127.2, 126.7, 124.6, 90.2, 88.0, 73.0, 28.6, 23.3, 16.8. ESI-FTMS: m/z calcd for C41H44N3O2 + [M + H]+: 610.3428; found: 610.3434. [α]D 26 –42.9 (c 1.05, CHCl3). FTIR: 2956, 2924, 2854, 1456, 1377, 1003, 938, 813, 755, 728, 700 cm–1.
  • 20 General Procedure for the Catalytic Asymmetric Friedel–Crafts Reaction (Table 3, Entry 2) PyBodine(Val) (L3, 0.011 mmol) and Cu(OAc)2 (0.01 mmol) were added to a round flask containing a stir bar under Ar. CH2Cl2 (1 mL) was added to the flask, and the mixture was stirred for 1 h. After cooling to 0 °C to the mixture was added nitroalkene (0.4 mmol), indole (0.2 mmol), and HFIP. After being stirred for appropriate time, the reaction mixture was purified by silica gel column chromatography (hexane–EtOAc; 9:1 to 2:1) to afford the Friedel–Crafts adduct. Analytical Data of 3b 1H NMR (400 MHz, CDCl3): δ = 7.99 (br s, 1 H), 7.36–7.30 (m, 4 H), 7.28–7.23 (m, 3 H), 7.02 (dd, J = 8.5 Hz, 1.4 Hz, 1 H) 6.96 (d, J = 1.8 Hz, 1 H), 5.16 (t, J = 8.4 Hz, 1 H), 5.05 (dd, J = 12.6, 8.4 Hz, 1 H), 4.93 (dd, J = 12.6, 8.4 Hz, 1 H), 2.17 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 139.2, 134.8, 129.3, 128.9, 127.7, 127.5, 126.3, 124.3, 121.8, 118.4, 113.9, 111.0, 79.5, 41.5, 21.5. ESI-FTMS: m/z calcd for C17H15N2O2 – [M – H]–: 279.1139; found: 279.1148; the enantiomeric excess was determined by HPLC with a Chiralcel OD-H column [hexane–2-PrOH (85:15), 0.7 mL/min, 254 nm]: t R (major enantiomer) = 50.0 min; t R (minor enantiomer) = 71.7 min. [α]D 20 +13.5 (c 1.0, CH2Cl2, 87% ee). FTIR: 3412, 2974, 1556, 1377 cm–1.
  • 22 Analytical Data of 3l 1H NMR (400 MHz, acetone-d 6): δ = 10.23 (br s, 2 H), 7.51–7.46 (m, 2 H), 7.43 (s, 4 H), 7.38–7.36 (m, 4 H), 7.10–7.06 (m, 2 H), 6.97–6.93 (m, 2 H), 5.30–5.14 (m, 6 H). 13C NMR (100 MHz, acetone-d 6): δ = 140.0, 137.4, 128.7, 127.0, 122.7, 122.3, 119.6, 119.2, 114.4, 112.0, 79.8, 41.5. ESI-FTMS: m/z calcd for C26H21N4O4 – [M – H]–: 453.1568; found: 453.1588; the enantiomeric excess was determined by HPLC with a Chiralcel AD-H column [hexane–2-PrOH (80:20), 1.0 mL/min, 254 nm]: t R (major enantiomer) = 44.7 min; t R (minor enantiomer) = 48.2 min. [α]D 20 +19.0 (c 1.0, CH2Cl2, 97% ee). FTIR: 3412, 2921, 1546, 1457, 741 cm–1.