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.

1. Synthesis of tricarbonyl(tropone)iron (1)19
<ol>
	<li>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...

<ol>
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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formal+aza-Michael+additions+to+tropone:+Addition+of+diverse+aryl-+and+alkylamines+to+tricarbonyl(tropone)iron+and+[(C7H7O)Fe(CO)3]BF4.">Formal aza-Michael additions to tropone: Addition of diverse aryl- and alkylamines to tricarbonyl(tropone)iron and [(C7H7O)Fe(CO)3]BF4.</a> Tetrahedron Letters. 59 (37), 3432-3434 (2018).</li><li>Pauson, P. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tropones+and+Tropolones.">Tropones and Tropolones.</a> Chemical Reviews. 55 (1), 9-136 (1955).</li><li>Pietra, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Seven-Membered+Conjugated+Carbo-and+Heterocyclic+Compounds+and+Their+Homoconjugated+Analogs+and+Metal+Complexes.+Synthesis,+Biosynthesis,+Structure,+and+Reactivity.">Seven-Membered Conjugated Carbo-and Heterocyclic Compounds and Their Homoconjugated Analogs and Metal Complexes. Synthesis, Biosynthesis, Structure, and Reactivity.</a> Chemical Reviews. 73 (4), 293-364 (1973).</li><li>Johnson, B. F. G., Lewis, J., Wege, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transition+metal+carbonyl+complexes+derived+from+cycloocta-2,4,6-trienone+and+cyclohepta-2,4,6-trienone.">Transition metal carbonyl complexes derived from cycloocta-2,4,6-trienone and cyclohepta-2,4,6-trienone.</a> Journal of the Chemical Society, Dalton Transactions. 1976, 1874-1880 (1976).</li><li>Franck-Neumann, M., Brion, F., Martina, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Friedel-Crafts+acylation+of+tropone-irontricarbonyl.+Synthesis+of+&#946;-thujaplicin+and+&#946;-dolabrin.">Friedel-Crafts acylation of tropone-irontricarbonyl. Synthesis of &#946;-thujaplicin and &#946;-dolabrin.</a> Tetrahedron Letters. 19 (50), 5033-5036 (1978).</li><li>Saha, M., Bagby, B., Nicholas, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cobalt-mediated+propargylation/annelation:+Total+synthesis+of+(&#177;)-cyclocolorenone.">Cobalt-mediated propargylation/annelation: Total synthesis of (&#177;)-cyclocolorenone.</a> Tetrahedron Letters. 27 (8), 915-918 (1986).</li><li>Yeh, M. -. C. P., Hwu, C. -. C., Ueng, C. -. H., Lue, H. -. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Michael+Addition+Reactions+of+the+Highly+Functionalized+Zinc-Copper+Reagents+RCu(CN)ZnI+to+(Tropone)iron+Tricarbonyl+Promoted+by+Boron+Trifluoride+Etherate.">Michael Addition Reactions of the Highly Functionalized Zinc-Copper Reagents RCu(CN)ZnI to (Tropone)iron Tricarbonyl Promoted by Boron Trifluoride Etherate.</a> Organometallics. 13 (5), 1788-1794 (1994).</li><li>Pearson, A. J., Srinivasan, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Approaches+to+the+synthesis+of+heptitol+derivatives+via+iron-mediated+stereocontrolled+functionalization+of+cycloheptatrienone.">Approaches to the synthesis of heptitol derivatives via iron-mediated stereocontrolled functionalization of cycloheptatrienone.</a> The Journal of Organic Chemistry. 57 (14), 3965-3973 (1992).</li><li>Souli&#233;, J., Betzer, J. -. F., Muller, B., Lallemand, J. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=General+access+to+polyhydroxylated+nortropane+derivatives+through+hetero+diels+-alder+cycloaddition.">General access to polyhydroxylated nortropane derivatives through hetero diels -alder cycloaddition.</a> Tetrahedron Letters. 36 (52), 9485-9488 (1995).</li><li>Rigby, J. H., Ogbu, C. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tricarbonyl(tropone)iron+as+a+useful+functionalized+enone+equivalent.">Tricarbonyl(tropone)iron as a useful functionalized enone equivalent.</a> Tetrahedron Letters. 31 (24), 3385-3388 (1990).</li><li>Franck-Neumann, M., Martina, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cycloadditions+de+la+tropone+avec+le+cyclopentadiene+synthese+d&#8217;un+intermediaire+potentiel+par+utilisation+de+complexe+metallique.">Cycloadditions de la tropone avec le cyclopentadiene synthese d&#8217;un intermediaire potentiel par utilisation de complexe metallique.</a> Tetrahedron Letters. 18 (26), 2293-2296 (1977).</li><li>Ban, T., Nagai, K., Miyamoto, Y., Harano, K., Yasuda, M., Kanematsu, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Periselective+cycloaddition+of+tricarbonyliron+complexes+of+seven-membered+unsaturated+compounds+with+1,2,4,5-tetrazine.+Masking+and+activating+effects+of+tricarbonyliron+complexes.">Periselective cycloaddition of tricarbonyliron complexes of seven-membered unsaturated compounds with 1,2,4,5-tetrazine. Masking and activating effects of tricarbonyliron complexes.</a> The Journal of Organic Chemistry. 47 (1), 110-116 (1982).</li><li>Bonadeo, M., Gandolfi, R., De Micheli, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactions+of+nitrile+oxides+and+of+2,5-dimethyl-3,4-diphenylcyclopentadienone+with+tricarbonyltroponeiron+and+oxidation+of+the+adducts+with+cerium(IV).">Reactions of nitrile oxides and of 2,5-dimethyl-3,4-diphenylcyclopentadienone with tricarbonyltroponeiron and oxidation of the adducts with cerium(IV).</a> Gazzetta Chimica Italiana. 107, 577-578 (1977).</li><li>Eisenstadt, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+reactivity+of+cycloheptadienyl-1-one+iron+tricarbonyl+cation+towards+nucleophilic+attack.">The reactivity of cycloheptadienyl-1-one iron tricarbonyl cation towards nucleophilic attack.</a> Journal of Organometallic Chemistry. 113 (2), 147-156 (1976).</li><li>Rosenblum, M., Watkins, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cyclopentannulation+reactions+with+organoiron+reagents.+Facile+construction+of+functionalized+hydroazulenes.">Cyclopentannulation reactions with organoiron reagents. Facile construction of functionalized hydroazulenes.</a> Journal of the American Chemical Society. 112 (17), 6316-6322 (1990).</li><li>Pearson, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Iron Compounds in Organic Synthesis. , (1994).</li><li>Eisenstadt, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluxional+behaviour+of+protonated+substituted+troponeiron+tricarbonyls.">Fluxional behaviour of protonated substituted troponeiron tricarbonyls.</a> Journal of Organometallic Chemistry. 97 (3), 443-451 (1975).</li><li>Shvo, Y., Hazum, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Simple+Method+for+the+Disengagement+of+Organic+Ligands+from+Iron+Complexes.">A Simple Method for the Disengagement of Organic Ligands from Iron Complexes.</a> Journal of the Chemical Society, Chemical Communications. , 336-337 (1974).</li><li>Thompson, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reaction+of+tricarbonylcyclohexadieneiron+complexes+with+cupric+chloride.">Reaction of tricarbonylcyclohexadieneiron complexes with cupric chloride.</a> Journal of Organometallic Chemistry. 108 (3), 381-383 (1976).</li><li>Franck-Neumann, M., Heitz, M. P., Martina, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Une+methode+simple+de+liberation+des+ligands+organiques+de+leurs+complexes+de+fer+carbonyle.">Une methode simple de liberation des ligands organiques de leurs complexes de fer carbonyle.</a> Tetrahedron Letters. 24 (15), 1615-1616 (1983).</li><li>Birch, A. J., Kelly, L. F., Liepa, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lateral+control+of+skeletal+rearrangement+by+complexation+of+thebaine+with+Fe(CO)3.">Lateral control of skeletal rearrangement by complexation of thebaine with Fe(CO)3.</a> Tetrahedron Letters. 26 (4), 501-504 (1985).</li><li>Ripoche, I., Gelas, J., Gr&#233;e, D., Gr&#233;e, R., Troin, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+stereoselective+synthesis+of+chiral+optically+pure+4-piperidones.">A new stereoselective synthesis of chiral optically pure 4-piperidones.</a> Tetrahedron Letters. 36 (37), 6675-6678 (1995).</li><li>Williams, I., Kariuki, B. M., Reeves, K., Cox, L. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereoselective+Synthesis+of+2-Dienyl-Substituted+Pyrrolidines+Using+an+&#951;4-Dienetricarbonyliron+Complex+as+the+Stereodirecting+Element:+Elaboration+to+the+Pyrrolizidine+Skeleton.">Stereoselective Synthesis of 2-Dienyl-Substituted Pyrrolidines Using an &#951;4-Dienetricarbonyliron Complex as the Stereodirecting Element: Elaboration to the Pyrrolizidine Skeleton.</a> Organic Letters. 8, 4389-4392 (2006).</li><li>Coquerel, Y., Depres, J. -. P., Greene, A. 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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...

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 tropone5. The resulting adduct contains several functional handles for subsequent synthetic elaboration to diverse complex seven-membered ring-containing scaffolds that would be otherwise difficult to access.
While previous work with tropone6,7 suggests that it would not be suitable for such a transformation, the related organometallic complex tricarbonyl(tropone)iron8 (1, Figure 1) has proven to be a versatile synthetic building block that has been utilized in the synthesis of a number of natural products and complex molecules9,10,11,12,13. Furthermore, the uncomplexed double bond of tricarbonyl(tropone)iron has been shown to behave similar to an &#945;,&#946;-unsaturated ketone in reactions with, for example, dienes14,15, tetrazines16, nitrile oxides17, diazoalkanes8,10, and organocopper reagents11. Thus, we envisioned that an aza-Michael reaction of tricarbonyl(tropone)iron would provide an efficient entry to synthetically valuable aminated tropone derivatives.
Eisenstadt had previously reported that, following protonation of tricarbonyl(tropone)iron, the resulting cationic complex 2 (Figure 1) could undergo nucleophilic attack by aniline or tert-butylamine to produce aminated derivatives of the tropone iron complex.18 However, the synthetic potential of this method remains unrealized. Indeed, no additions of other amines had been reported, and the demetallation of those products was not explored in Eisenstadt&#8217;s report. We have adapted this protocol to demonstrate the addition of a wide variety of amine nucleophiles.
We also describe a method for direct aza-Michael additions to tricarbonyl(tropone)iron (Figure 2), which does not require synthesis of the cationic complex and generally proceeds in higher yields compared to the previously reported method. We also report herein a protocol for the demetallation of the resulting adducts. Overall, this protocol provides formal aza-Michael adducts of tropone in four steps from tropone (and three steps from the known iron complex).

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	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">10 g SNAP Ultra silica gel columns</td>
			<td style="width:145px;">Biotage</td>
			<td style="width:119px;"></td>
			<td style="width:197px;">for automated column chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Acetic anhydride</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">A10-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Acetone</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">A-16S-20</td>
			<td>for cooling baths</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Acetonitrile-D3</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">366544</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Benzene, anhydrous, 99.8%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">401765</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Biotage Isolera Prime</td>
			<td style="width:145px;">Biotage</td>
			<td style="width:119px;">ISO-PSF</td>
			<td>for automated chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Celite; 545 Filter Aid</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">C212-500</td>
			<td>diatomaceous earth</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">Cerium(IV) ammonium nitrate, ACS, 99+%</td>
			<td style="width:145px;">Alfa Aesar</td>
			<td align="right" style="width:119px;">33254</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Chloroform-D</td>
			<td style="width:145px;">Acros</td>
			<td align="right" style="width:119px;">209561000</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Di-tert-butyl dicarbonate, 99%</td>
			<td style="width:145px;">Acros</td>
			<td align="right" style="width:119px;">194670250</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Ethyl acetate</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">E145-4</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">Ethyl alcohol, absolute - 200 proof</td>
			<td style="width:145px;">Greenfield Global</td>
			<td style="width:119px;">111000200PL05</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Ethyl ether anhydrous</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">E138-1</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Hexanes</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">H302-4</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">iron nonacarbonyl 99%</td>
			<td style="width:145px;">Strem</td>
			<td style="width:119px;">26-2640</td>
			<td>air sensitive, synonymous with diiron nonacarbonyl</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Magnesium sulfate</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">M65-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Methanol</td>
			<td style="width:145px;">EMD Millipore</td>
			<td style="width:119px;">MX0475-1</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Methylene chloride</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">D37-4</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">MP alumina, Act. II-III acc. To Brockmann</td>
			<td style="width:145px;">MP Biomedicals</td>
			<td align="right" style="width:119px;">4691</td>
			<td>for column chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">o-toluidine 98%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">466190</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Phenethylamine 99%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">128945</td>
			<td>distill prior to use if not colorless</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium bicarbonate</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S233-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium carbonate anhydrous</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S263-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium chloride</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S271-500</td>
			<td>dissolved in deionized water to perpare a saturated aqueous solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium sulfate anhydrous</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S415-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sonicator</td>
			<td style="width:145px;">Branson</td>
			<td style="width:119px;"></td>
			<td>model 2510</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sulfuric acid</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">A300C-212</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">Tetrafluoroboric acid solution, 48 wt.%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">207934</td>
			<td>aqueous solution</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">TLC Aluminium oxide 60 F254, neutral</td>
			<td style="width:145px;">EMD Millipore</td>
			<td style="width:119px;">1.05581.0001</td>
			<td>for thin layer chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Tropone 97%</td>
			<td style="width:145px;">Alfa Aesar</td>
			<td style="width:119px;">L004730-06</td>
			<td>Light sensitive</td>
		</tr>
	</tbody>
</table>

preparation of 6-aminocyclohepta-2,4-dien-1-one derivatives via tricarbonyl(tropone)iron

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.

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 &#951;4-diene ligand give rise to the signals at 6.39 ppm (...

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Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

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

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate ...

This protocol is an efficient method for the synthesis of aminated tropone derivatives. These compounds can serve as synthetic intermediates for the synthesis of structurally complex amines. An advantage of this technique is that the aza-Micheal addition can be accomplished in a solvent free process with many amine substrates.This simplifies reaction setup and product isolation. Add a PTFE magnetic stir bar, 150 milligrams of tricarbonyl tropone iron and 0.154 milliliters of phenylethylamine to a one dram vial. Cap the vial under an air atmosphere and commence magnetic stirring.Monitor the reaction periodically by removing a small aliquot from the reaction mixture, dissolving in deuterated chloroform, and acquiring a proton NMR spectrum. Observe for disappearance of the signals for tricarbonyl tropone iron in the proton NMR spectrum. Upon their disappearance, purify the crude reaction mixture via chromatography on basic alumina.Pack a 30 millimeter diameter chromatography column with alumina and hexanes. Apply the crude reaction mixture to the top of the column. Elute the column with one to one hexanes to diethyl ether to remove the excess phenylethylamine from the column.Monitor the elution via thin layer chromatography. After the excess amine has finished eluting change the eluting solvent to one to one diethyl ether to methylene chloride to elute the product. Add a PTFE stir bar to 0.021 milliliters of o-toluidene and 1.0 milliliter of diethyl ether to a one dram vial.Commence vigorous magnetic stirring. Then carefully add 33 milligrams of the cationic complex to the mixture. Allow the suspension to stir for 12 hours.After 12 hours, pour the reaction mixture into five milliliters of deionized water in a separatory funnel. Then, extract the aqueous layer with 5 milliliters of ethyl acetate three times. Wash the combined organic layers with 10 milliliters of brine before drying over anhydrous sodium sulfate.Then remove the sodium sulfate by gravity filtration. Concentrate the filtrate via rotary evaporation to obtain the crude product for purification via column chromatography on basic alumina. Dissolve 76 milligrams of amine four in two milliliters of absolute ethanol in a 25 milliliter round-bottom flask under air atmosphere.Then, add 104 milligrams of di-tert-butyl dicarbonate followed by 40 milligrams of solid sodium bicarbonate to the reaction mixture. Cap the flask with a rubber septum and sonicate the mixture for one hour. Filter the crude reaction mixture through a bed of diatomaceous earth using a Buchner funnel.Wash the diatomaceous earth with ethanol until no more brown colored solution comes out of the bottom of the funnel. Transfer the filtrate to a round-bottom flask and concentrate on a rotary evaporator. Dissolve the resulting oil in approximately 2.5 milliliters of methylene chloride.Add approximately 1.3 grams of silica gel to the solution, then remove the methylene chloride on the rotary evaporator until a fine free flowing solid is obtained. Now, pack the silica gel into a 10 gram silica cartridge for automated flash chromatography. Run the column using a gradient starting from 90 to 10 hexanes to ethyl acetate and ending at 20 to 80 hexanes to ethyl acetate over a period of 20 minutes.Collect the fractions containing the product as indicated by the major peak detected at 254 nanometers absorbance. In a 10 milliliter round-bottom flask dissolve 27 milligrams of iron complex five in one milliliter of methanol under air atmosphere and immerse the flask in an ice bath. Commence magnetic stirring and add 33 milligrams of cerium four ammonium nitrate.After 30 minutes add a second 33 milligram portion of cerium four ammonium nitrate followed by a third 33 milligram portion after an additional 30 minutes of stirring. After adding the third portion of cerium four ammonium nitrate, dilute the reaction mixture with five milliliters of ethyl acetate. Pour the mixture into a 30 milliliter separatory funnel containing 5 milliliters of saturated aqueous sodium bicarbonate.Separate the layers. Re-extract the aqueous layer with ethyl acetate. Then, dry the combined organic layers over anhydrous sodium sulfate before performing the final purification steps as described in the text protocol.The proton NMR data for the cationic iron complex features seven distinct multiplets, including signals arising from diastereotopic alpha methylene protons. Shown here are the proton and carbon 13 NMR data for the o-toluidine adduct three prepared via cationic complex two which contains the same features as the phenylethylamine adduct four. The proton NMR spectrum is characterized by signals arising from the iron complexed diene and the diastereotopic alpha methylene protons.Shown here are the proton and carbon 13 NMR spectra of tert-butyl carbamate five. The proton NMR spectrum is characterized by its broad peaks caused by slow rotation of the carbamate carbon nitrogen bond relative to the NMR time scale. In addition, the presence of the tert-butyl carbamate is evident from the large singlet at 1.5 ppm from the tert-butyl protons.As well as the signal at 154.3 ppm in the carbon 13 NMR spectrum corresponding to the carbonyl carbon of the carbamate group. Upon decomplexation of the diene from the iron, the most notable aspect of the proton NMR spectrum is the presence of four signals between 5.75 and 6.75 ppm corresponding to the protons from the uncomplexed diene. The compound synthesized using this protocol contains several functional groups which enables the synthesis of a diverse collection of complex amines that contain a seven membered ring.This protocol involves the use of flammable solvents and toxic reagents. Reaction and purifications must be performed in a fume hood. Safety glasses and gloves must be worn.

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7.8K Views.  Lafayette College. This protocol is an efficient method for the synthesis of aminated tropone derivatives. These compounds can serve as synthetic intermediates for the synthesis of structurally complex amines. An advantage of this technique is that the aza-Micheal addition can be accomplished in a solvent free process with many amine substrates.This simplifies reaction setup and product isolation. Add a PTFE magnetic stir bar, 150 milligrams of tricarbonyl tropone iron and 0.154 milliliters of phenylethy...