Synthesis of N-Fmoc-Protected Amino Alkyl Thiocyanates/Selenocyanates and Their Application in the Preparation of 5-Substituted S/Se-Linked Tetrazoles

Abstract

A novel class of N-Fmoc-protected amino alkyl thiocyanates/selenocyanates has been prepared by thiocyanation/selenocyanation of the corresponding alkyl iodides. These thiocyanates/selenocyanates undergo a facile [2+3]-cycloaddition reaction with sodium azide to afford novel N-Fmoc amino alkyl S/Se-linked tetrazoles.

Key words

amino acid derivatives - thiocyanates - selenocyanates - [2+3] cycloaddition - S/Se-linked tetrazoles

References

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• 30b

  To a solution of 2i in i-PrOH-H₂O (7:3), NaOH (1.1 equiv) and CaCl₂ (0.8 M) were added and the reaction mixture was stirred at room temperature until completion.

29

The HPLC chromatogram of Fmoc-Phg-ψ(CH₂NCS) had a peak at t _R 19.70 minutes while Fmoc-Phg-ψ(CH₂SCN) eluted at t _R 14.49 minutes, which confirmed the absence of the undesired isomer in the thiocyanate product.

31

The RP-HPLC spectrum of H-Ala-ψ(CH₂SCN₄H)(10a) had a single peak at t _R 14.2 minutes. The same compound exhibited a distinct methyl group doublet in its ^¹H NMR spectrum. These two observations confirmed the enantiomeric purity of the free amino tetrazole derivative.