PDF herunterladen
Synlett 2014; 25(4): 491-494
DOI: 10.1055/s-0033-1340598
letter
© Georg Thieme Verlag Stuttgart · New York

Benzo[d]imidazole and Aliphatic α-Amino Acid Derived Primary Amines in Asymmetric Aldol Reactions

Pravinkumar Hansraj Mohite
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice, 53210, Czech Republic   Fax: +420(46)6037068   eMail: filip.bures@upce.cz
,
Pavel Drabina
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice, 53210, Czech Republic   Fax: +420(46)6037068   eMail: filip.bures@upce.cz
,
Filip Bureš*
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice, 53210, Czech Republic   Fax: +420(46)6037068   eMail: filip.bures@upce.cz
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 12. November 2013

Accepted after revision: 11. Dezember 2013

Publikationsdatum:
14. Januar 2014 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

Starting from essential α-amino acids, four new benzo[d]imidazole and alkyl-chain-substituted primary amines were synthesized. The reaction sequence involves activation of the Boc-amino acid carboxylic acid, reaction with o-phenylenediamine, and subsequent cyclization to benzo[d]imidazole. N-Methylation and final Boc group removal afforded four new primary amines. The synthesized amines were preliminarily applied as organocatalysts in an asymmetric version of the aldol reaction between 4-nitrobenzaldehyde and acetone/cyclohexanone, achieving chemical yields of 40–64% and ee and de values up to 65 and 96%, respectively.

Key words

benzo[d]imidazole - primary amine - α-amino acid - asymmetric aldol reaction - organocatalysis

Supporting Information

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

  • References and Notes

  • 1 Modern Aldol Reactions . Vol. 1 and 2. Mahrwald R. Wiley-VCH; Weinheim: 2004
    CrossrefSuche in Google Scholar
  • 2 Enantioselective Organocatalysis: Reactions and Experimental Procedures. Dalko PI. Wiley-VCH; Weinheim: 2007
    CrossrefSuche in Google Scholar
  • 8 Synthesis of (S)-4; Typical Procedure: Methyl chloroformate (1.6 mL, 21.2 mmol) was added to a mixture of (S)-N-Boc-ILe (4.9 g, 21.2 mmol), triethylamine (3.0 mL, 21.2 mmol), and DMF (18 mL) at –20 °C. After 15 min stirring, o-phenylenediamine (2.3 g, 21.2 mmol) was added and the reaction was stirred at 20 °C for 4 h. The solvent was evaporated and the residue was partitioned between H2O and EtOAc. The organic layer was washed with NaHCO3 (5% aq.), brine, H2O, dried (Na2SO4), and the solvent was evaporated to afford amino-amide 8 (5.7 g, 80%). A solution of 8 (5.7 g, 20.0 mmol) in glacial AcOH (10 mL) was heated at 65 °C for 1 h, then the solvent was evaporated and the residue was partitioned between H2O and EtOAc. The organic layer was washed with H2O, dried (Na2SO4), and the solvent was evaporated. Crystallization of the residue from Et2O–hexane afforded benzo[d]imidazole derivative 12 (3.9 g, 76%). Derivative 12 (1.2 g, 3.8 mmol) dissolved in anhydrous THF (20 mL) was treated with LHMDS (1 M in THF, 3.8 mL, 3.8 mmol) at 0 °C for 30 min, whereupon iodomethane (0.25 mL, 4.0 mmol) was added and the reaction was stirred at 20 °C for 3 h. The reaction was diluted with H2O and extracted with EtOAc. The organic layer was dried (Na2SO4), the solvents were evaporated, and the residue was purified by column chromatography (SiO2; EtOAc–hexane, 1:1) to gave N-methyl derivative 16 (772 mg, 64%). Boc derivative 16 (730 mg, 2.3 mmol) was treated with TFA (1 mL) at 20 °C for 1 h, then Et2O–hexane (1:1) was added to the reaction mixture until the product precipitated. The crude product was filtered and purified by column chromatography (SiO2; EtOAc–CH2Cl2–MeOH, 1:1:0.2) to afford (S)-4 (180 mg, 36%) as a viscous oil. [α]D 20 –21.8 (c 1, MeOH). 1H NMR (400 MHz, DMSO-d 6): δ = 0.85 (d, J = 6.4 Hz, 3 H, CH2CH 3), 0.90 (t, J = 7.2 Hz, CHCH 3), 1.19 and 1.75 (2 × m, 2 × 1 H, CH 2), 1.90 (m, 1 H, CH), 3.85 (s, 3 H, NCH 3), 4.03 (d, J = 7.6 Hz, 1 H, NH2CH), 7.20–7.55 (m, 2 H, CH Ar), 7.56 (d, J = 7.0 Hz, 1 H, CH Ar), 7.62 (d, J = 7.0 Hz, 1 H, CH Ar). 13C NMR (100 MHz, DMSO-d 6): δ = 11.20, 15.78, 24.06, 29.80, 39.92, 52.30, 110.02, 118.51, 121.35, 121.62, 135.68, 141.92, 157.67. MALDI-HRMS (DHB): m/z [M+H]+ calcd for C13H20N3 +: 218.1652; found: 218.1645.
  • 9 Balboni G, Guerrini R, Salvadori S, Bianchi C, Rizzi D, Bryant SD, Lazarus LH. J. Med. Chem. 2002; 45: 713
    CrossrefSuche in Google Scholar
  • 10 Lacoste E, Landais Y, Schenk K, Verlhac J.-B, Vincent J.-M. Tetrahedron Lett. 2004; 45: 8035
    CrossrefSuche in Google Scholar
  • 11 Aldol Reaction; General Procedure: A solution of catalyst 1–4 (0.09 mmol) in acetone or cyclohexanone (7.5 mL) was treated with TFA (3.5 μL, 0.045 mmol) at 20 °C for 5 min, whereupon 4-nitrobenzaldehyde (151 mg, 1.0 mmol) was added and the reaction was stirred for 24 h. The solvent was evaporated and the residue was purified by column chromatography (SiO2; EtOAc–hexane, 1:1).
  • 12 Enantiomeric excesses were determined by chiral phase HPLC. For 17: Daicel Chiralpak AS-H; n-hexane–i-PrOH, 70:30; flow rate 0.5 mL/min; λ = 254 nm, t R = 25.32, 33.65 min. For 18: Daicel Chiralpak AD-H; n-hexane–i-PrOH, 80:20; flow rate 0.5 mL/min; λ = 254 nm; t R = 22.69 (syn), 24.34 (syn), 26.35 (anti), 33.26 (anti) min.