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Journal of the Iranian Chemical Society

, Volume 15, Issue 10, pp 2175–2181 | Cite as

A novel strategy for the asymmetric synthesis of (S)-ketamine using (S)-tert-butanesulfinamide and 1,2-cyclohexanedione

  • Mohammad Javad Taghizadeh
  • Seyed Jamal Addin Gohari
  • Abdollah Javidan
  • Abolghasem Moghimi
  • Maryam Iman
Original Paper
  • 93 Downloads

Abstract

We present a novel asymmetric synthesis route for synthesis of (S)-ketamine using a chiral reagent according to the strategy (Scheme 1), with good enantioselectivity (85% ee) and yield. In this procedure, the (S)-tert-butanesulfinamide (TBSA) acts as a chiral auxiliary reagent to generate (S)-ketamine. A series of new intermediates were synthesized and identified for the first time in this work (2–4). The monoketal intermediate (1) easily obtained after partial conversion of one ketone functional group  of 1,2-cyclohexanedione into a ketal using ethylene glycol. The sulfinylimine (2) was obtained by condensation of (S)-tert-butanesulfinamide (TBSA) with (1), 4-dioxaspiro[4.5]decan-6-one in 90% yield. The (S)-N-tert-butanesulfinyl ketamine (3) was prepared on further reaction of sulfinylimine (2) with appropriate Grignard reagent (ArMgBr) in which generated chiral center in 85% yield and with 85% diastereoselectivity. Methylation of amine afforded the product (4). Finally, the sulfinyl- and ketal-protecting groups were removed from the compound (4) by brief treatment with stoichiometric quantities of HCl in a protic solvent gave the (S)-ketamine in near quantitative yield.

Graphical abstract

Keywords

(S)-Ketamine Asymmetric synthesis (S)-tert-Butanesulfinamide 1,2-Cyclohexanedione Monoketal Enantioselective construction 

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Copyright information

© Iranian Chemical Society 2018

Authors and Affiliations

  • Mohammad Javad Taghizadeh
    • 1
  • Seyed Jamal Addin Gohari
    • 1
  • Abdollah Javidan
    • 1
    • 2
    • 3
  • Abolghasem Moghimi
    • 1
  • Maryam Iman
    • 4
  1. 1.Department of Chemistry, Faculty of ScienceImam Hossein UniversityTehranIran
  2. 2.Department of Medicine Chemistry, Faculty of Science Pharmaceutical Sciences BranchIslamic Azad UniversityTehranIran
  3. 3.University of EyvanekeyEyvankiIran
  4. 4.Department of Chemistry, Faculty of ScienceBaghyatollah Medical Sciences UniversityTehranIran

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