A subscription to JoVE is required to view this content. Sign in or start your free trial.
Representative experimental procedures for the addition of amine nucleophiles to tricarbonyl(tropone)iron and subsequent demetallation of the resulting complexes are presented in detail.
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.
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....
1. Synthesis of tricarbonyl(tropone)iron (1)19
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 (.......
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.......
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.
....Name | Company | Catalog Number | Comments |
10 g SNAP Ultra silica gel columns | Biotage | for automated column chromatography | |
Acetic anhydride | Fisher Scientific | A10-500 | |
Acetone | Fisher Scientific | A-16S-20 | for cooling baths |
Acetonitrile-D3 | Sigma Aldrich | 366544 | |
Benzene, anhydrous, 99.8% | Sigma Aldrich | 401765 | |
Biotage Isolera Prime | Biotage | ISO-PSF | for automated chromatography |
Celite; 545 Filter Aid | Fisher Scientific | C212-500 | diatomaceous earth |
Cerium(IV) ammonium nitrate, ACS, 99+% | Alfa Aesar | 33254 | |
Chloroform-D | Acros | 209561000 | |
Di-tert-butyl dicarbonate, 99% | Acros | 194670250 | |
Ethyl acetate | Fisher Scientific | E145-4 | |
Ethyl alcohol, absolute - 200 proof | Greenfield Global | 111000200PL05 | |
Ethyl ether anhydrous | Fisher Scientific | E138-1 | |
Hexanes | Fisher Scientific | H302-4 | |
iron nonacarbonyl 99% | Strem | 26-2640 | air sensitive, synonymous with diiron nonacarbonyl |
Magnesium sulfate | Fisher Scientific | M65-500 | |
Methanol | EMD Millipore | MX0475-1 | |
Methylene chloride | Fisher Scientific | D37-4 | |
MP alumina, Act. II-III acc. To Brockmann | MP Biomedicals | 4691 | for column chromatography |
o-toluidine 98% | Sigma Aldrich | 466190 | |
Phenethylamine 99% | Sigma Aldrich | 128945 | distill prior to use if not colorless |
Sodium bicarbonate | Fisher Scientific | S233-500 | |
Sodium carbonate anhydrous | Fisher Scientific | S263-500 | |
Sodium chloride | Fisher Scientific | S271-500 | dissolved in deionized water to perpare a saturated aqueous solution |
Sodium sulfate anhydrous | Fisher Scientific | S415-500 | |
Sonicator | Branson | model 2510 | |
Sulfuric acid | Fisher Scientific | A300C-212 | |
Tetrafluoroboric acid solution, 48 wt.% | Sigma Aldrich | 207934 | aqueous solution |
TLC Aluminium oxide 60 F254, neutral | EMD Millipore | 1.05581.0001 | for thin layer chromatography |
Tropone 97% | Alfa Aesar | L004730-06 | Light sensitive |
This article has been published
Video Coming Soon
ABOUT JoVE
Copyright © 2024 MyJoVE Corporation. All rights reserved