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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

Representative experimental procedures for the addition of amine nucleophiles to tricarbonyl(tropone)iron and subsequent demetallation of the resulting complexes are presented in detail.

Abstract

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate in a direct aza-Michael reaction with tricarbonyl(tropone)iron under solvent-free conditions. Less nucleophilic aniline derivatives and more hindered secondary amines add efficiently to the cationic tropone complex formed by protonation of tricarbonyl(tropone)iron. While the protocol utilizing the cationic complex is less efficient overall for accessing the aza-Michael adducts than the direct, solvent-free addition to the neutral complex, it allows the use of a broader range of amine nucleophiles. Following protection of the amine of the aza-Michael adduct as a tert-butyl carbamate, the diene is decomplexed from the iron tricarbonyl fragment upon treatment with cerium(IV) ammonium nitrate to provide derivatives of 6-aminocyclohepta-2,4-dien-1-one. These products can serve as precursors to diverse compounds containing a seven-membered carbocyclic ring. Because the demetallation requires protection of the amine as a carbamate, the aza-Michael adducts of secondary amines cannot be decomplexed using the protocol described here.

Introduction

Structurally complex amines containing a seven-membered carbocyclic ring are common to a number of biologically active molecules. Notable examples include the tropane alkaloids1 and several members of the Lycopodium2, Daphniphyllum3, and monoterpenoid indole alkaloid4 families. However, such compounds are often more difficult to synthesize compared to compounds of similar complexity containing only five- or six-membered rings. Thus, we sought to develop a new avenue towards such compounds by attaching diverse amine nucleophiles to tropone....

Protocol

1. Synthesis of tricarbonyl(tropone)iron (1)19

  1. In an argon-atmosphere glovebox, weigh out 4.1 g of diiron nonacarbonyl into an oven-dried 20 mL vial. Cap the vial and remove it from the glovebox.
    CAUTION: Prolonged storage of diiron nonacarbonyl leads to some deterioration to give triiron dodecacarbonyl and finely divided metallic iron20. This deterioration is evidenced by the presence of a black solid within the shiny orange diiron nonacarbonyl. The iron.......

Representative Results

All novel compounds in this study were characterized by 1H and 13C NMR spectroscopy and high resolution mass spectrometry. Previously reported compounds were characterized by 1H NMR spectroscopy. NMR data for representative compounds are described in this section.

The 1H NMR spectrum of tricarbonyl(tropone)iron is shown in Figure 3. The protons of the η4-diene ligand give rise to the signals at 6.39 ppm (.......

Discussion

Whether the solvent-free protocol involving direct addition to tricarbonyl(tropone)iron (Figure 2) or the indirect method utilizing the corresponding cationic complex as the electrophile (Figure 1) is to be employed depends on the amine substrate used. In general, the direct addition method is preferable since it requires fewer steps to generate the aza-Michael adducts from tropone and the overall yields are generally higher. However, this more direct m.......

Acknowledgements

Acknowledgement is made to the Donors of the American Chemical Society Petroleum Research Fund for support of this research. We acknowledge the Lafayette College Chemistry Department and the Lafayette College EXCEL Scholars program for financial support.

....

Materials

NameCompanyCatalog NumberComments
10 g SNAP Ultra silica gel columnsBiotagefor automated column chromatography
Acetic anhydrideFisher ScientificA10-500
AcetoneFisher ScientificA-16S-20for cooling baths
Acetonitrile-D3Sigma Aldrich366544
Benzene, anhydrous, 99.8%Sigma Aldrich401765
Biotage Isolera PrimeBiotageISO-PSFfor automated chromatography
Celite; 545 Filter AidFisher ScientificC212-500diatomaceous earth
Cerium(IV) ammonium nitrate, ACS, 99+%Alfa Aesar33254
Chloroform-DAcros209561000
Di-tert-butyl dicarbonate, 99%Acros194670250
Ethyl acetateFisher ScientificE145-4
Ethyl alcohol, absolute - 200 proofGreenfield Global111000200PL05
Ethyl ether anhydrousFisher ScientificE138-1
HexanesFisher ScientificH302-4
iron nonacarbonyl 99%Strem26-2640air sensitive, synonymous with diiron nonacarbonyl
Magnesium sulfateFisher ScientificM65-500
MethanolEMD MilliporeMX0475-1
Methylene chlorideFisher ScientificD37-4
MP alumina, Act. II-III acc. To BrockmannMP Biomedicals4691for column chromatography
o-toluidine 98%Sigma Aldrich466190
Phenethylamine 99%Sigma Aldrich128945distill prior to use if not colorless
Sodium bicarbonateFisher ScientificS233-500
Sodium carbonate anhydrousFisher ScientificS263-500
Sodium chlorideFisher ScientificS271-500dissolved in deionized water to perpare a saturated aqueous solution
Sodium sulfate anhydrousFisher ScientificS415-500
SonicatorBransonmodel 2510
Sulfuric acidFisher ScientificA300C-212
Tetrafluoroboric acid solution, 48 wt.%Sigma Aldrich207934aqueous solution
TLC Aluminium oxide 60 F254, neutralEMD Millipore1.05581.0001for thin layer chromatography
Tropone 97%Alfa AesarL004730-06Light sensitive

References

  1. Pollini, G. P., Benetti, S., De Risi, C., Zanirato, V. Synthetic Approaches to Enantiomerically Pure 8-Azabicyclo[3.2.1]octane Derivatives. Chemical Reviews. 106, 2434-2454 (2006).
  2. Ma, X., Gang, D. R. The Lycopodium alkaloids.

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