Name: Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron (Video) | JoVE Journal
Uploaded: 2019-08-12T15:00:00.000+00:00
Duration: 7 min 56 s
Description: Learn solvent-free synthesis of aminated tropone derivatives via aza-Michael addition using tricarbonyl(tropone)iron complexes. This efficient method simplifies reaction setup and enables production of structurally complex amines.

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5 minutes

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 impurity is pyrophoric and can ignite upon exposure to air. Storing the diiron nonacarbonyl under argon at 2-8 &#176;C in a bottle sealed with electrical tape appears to minimize this deterioration. The pyrophoric iron impurities can be destroyed via addition of dilute hydrochloric acid.</li>
	<li>Add an oven-dried PTFE stir bar, 0.5 mL of tropone, and 10 mL of dry benzene to an oven-dried 50 mL round bottom flask. 
	NOTE: A round bottom flask with a 24/40 ground glass joint is preferred so that the solid diiron nonacarbonyl may be added rapidly with minimal spilling (see Step 1.5).</li>
	<li>Degas the contents of the round bottom flask via three freeze-pump-thaw cycles as follows.
	<ol>
		<li>Submerge the flask in a dry ice-acetone bath until the contents solidify completely. Then, with the flask still submerged in the cold bath, evacuate the flask under vacuum for 2-3 min.</li>
		<li>Allow the contents to thaw under static vacuum.</li>
		<li>Repeat steps 1.3.1 and 1.3.2 twice.</li>
		<li>After the final thaw, backfill the flask with argon and cover the flask with a rubber septum. Keep the flask under a positive pressure of argon.</li>
	</ol>
	</li>
	<li>Cover the flask with aluminum foil and commence vigorous magnetic stirring.</li>
	<li>Briefly remove the rubber septum and add the previously weighed diiron nonacarbonyl in a single portion and replace the septum.</li>
	<li>Immerse the flask in an oil bath at 55-60 &#176;C and stir for 30 min.</li>
	<li>After 30 min, remove the flask from the oil bath and allow to cool to room temperature.</li>
	<li>Isolate the tropone complex via alumina column chromatography as follows.
	<ol>
		<li>Pack a chromatography column (~30 mm diameter) with 12 cm of alumina (Activity II/III) and hexanes.</li>
		<li>Pipette the crude reaction mixture directly onto the alumina. Rinse the flask with a small amount (1-3 mL) of hexanes and add to the top of the column.</li>
		<li>Drain the column until the solvent is level with the top of the alumina and add ~2 cm of sand.</li>
		<li>Elute with hexanes until the blue-green band (triiron dodecacarbonyl) comes off the column.</li>
		<li>Elute with 1:1 hexanes:methylene chloride until the red-orange tropone iron complex elutes completely.</li>
		<li>Remove the solvent from the red-orange solution via rotary evaporation to obtain the tropone complex as a dark red oil that solidifies on standing. 
		NOTE: The tropone complex isolated in this fashion is occasionally contaminated with paramagnetic, iron-based impurities, as evidenced by severely broadened peaks in the 1H NMR spectrum. These impurities can be removed by redissolving the complex in methylene chloride&#160;and passing through a short plug of alumina, eluting with 1:1 hexanes:methylene chloride.</li>
	</ol>
	</li>
</ol>
2. Synthesis of tricarbonyl(5-ketocycloheptadienyl)iron tetrafluoroborate (2)21
<ol>
	<li>Add a PTFE magnetic stir bar, 432 mg of tricarbonyl(tropone)iron, and 10 mL of methylene chloride to a 50 mL round bottom flask.</li>
	<li>Cool the flask in an ice bath and commence vigorous magnetic stirring.</li>
	<li>Add 3.2 mL of concentrated sulfuric acid dropwise.</li>
	<li>Vigorously stir the mixture at 0 &#176;C for 30 min.</li>
	<li>To a separate 100 mL round bottom flask, add a PTFE stir bar, 2.0 g of anhydrous sodium carbonate, and 10 mL of methanol.</li>
	<li>Cool the flask containing the sodium carbonate mixture in an ice bath and vigorously stir it magnetically.</li>
	<li>Upon completion of the 30-min period (step 2.4), cease magnetic stirring. Two layers should form.</li>
	<li>Using a Pasteur pipette, transfer the viscous, brown lower layer to the rapidly stirring sodium carbonate suspension.</li>
	<li>Stir for ~5 min, and then carefully and slowly add 50 mL of deionized water. 
	CAUTION: Vigorous bubbling is involved in this step.</li>
	<li>Pour the mixture into a 250 mL separatory funnel and extract with methylene chloride (2x 50 mL).</li>
	<li>Sequentially wash the combined organic layers with water (50 mL) and brine (50 mL).</li>
	<li>Dry the organic layers over anhydrous magnesium sulfate.</li>
	<li>Remove the magnesium sulfate via gravity or vacuum filtration and concentrate the filtrate via rotary evaporation to obtain a red-brown oil. 
	NOTE: The protocol may be paused at this point.</li>
	<li>Add 3 mL of acetic anhydride to a 25 mL Erlenmeyer flask and cool it in an ice bath.</li>
	<li>Add 1 mL of 48% aqueous tetrafluoroboric acid to the cold acetic anhydride dropwise. 
	CAUTION: The addition is highly exothermic. However, the exotherm is readily contained by controlling the temperature and rate of addition.</li>
	<li>In a 100 mL round bottom flask submerged in an ice bath, add the mixture obtained from step 2.15 to the oil obtained in step 2.13.</li>
	<li>Agitate the mixture with a stainless steel spatula for 5 min. 
	NOTE: The mixture generally takes on a gummy consistency upon agitation and the color becomes lighter.</li>
	<li>Add 50 mL of diethyl ether to the mixture. Collect the resulting pale yellow solid via vacuum filtration using a Buchner funnel to obtain the cationic complex as its tetrafluoroborate salt.</li>
</ol>
3. Synthesis of aza-Michael adduct 4: Tricarbonyl[(2-5-h)-6-((2-phenylethyl)amino)cyclohepta-2,4-dien-1-one]iron
<ol>
	<li>Add a PTFE magnetic stir bar, 150 mg of tricarbonyl(tropone)iron (1), and 0.154 mL of phenethylamine to a 1-dram vial. Cap the vial under an air atmosphere and commence magnetic stirring. 
	NOTE: Phenethylamine will be oxidized by air upon prolonged storage resulting in a yellow-brown color. Phenethylamine should be distilled prior to use if it is not colorless.</li>
	<li>Monitor the reaction periodically by removing a small (~1 drop) aliquot from the reaction mixture, dissolving in CDCl3, and acquiring a 1H NMR spectrum. 
	NOTE: While this particular reaction is usually complete within 1 h, the reaction may be left to stir overnight.</li>
	<li>Upon disappearance of the signals for tricarbonyl(tropone)iron in the 1H NMR spectrum (see Representative Results and Figure 3 and Figure 4), purify the crude reaction mixture via chromatography on basic alumina (Activity II/III) as follows.
	<ol>
		<li>Pack a 30 mm diameter chromatography column with alumina (10-15 cm) and hexanes and apply the crude reaction mixture to the top of the column.</li>
		<li>Elute the column with 1:1 hexanes:diethyl either to remove the excess phenethylamine from the column. Monitor the elution via thin layer chromatography (TLC). 
		NOTE: The column was monitored using alumina TLC plates and a 1:1 diethyl ether:methylene chloride mixture as the mobile phase. If alumina TLC plates are not available, silica gel plates may be used (use 5% methanol in methylene chloride as the mobile phase).</li>
		<li>After the excess amine has finished eluting, change the eluting solvent to 1:1 diethyl ether:methylene chloride to elute the product. 
		NOTE: The title compound elutes as a yellow band.</li>
		<li>Combine the product-containing fractions (as judged by thin layer chromatography) and remove the solvent on a rotary evaporator to obtain the purified product as a dark yellow oil.</li>
	</ol>
	</li>
</ol>
4. Synthesis of tricarbonyl[(2-5-h)-6-(2-methylanilino)cyclohepta-2,4-dien-1-one]iron (3)
<ol>
	<li>Add a PTFE stir bar, 0.021 mL of o-toluidine, and 1.0 mL of diethyl ether to a 1-dram vial. Commence vigorous magnetic stirring.</li>
	<li>Carefully add 33 mg of the cationic complex to the mixture. Allow the suspension to stir for 12 h.</li>
	<li>Pour the reaction mixture into 5 mL of deionized water in a separatory funnel and extract the aqueous layter with 5 mL of ethyl acetate three times.</li>
	<li>Wash the combined organic layers with 10 mL of brine before drying over anhydrous sodium sulfate.</li>
	<li>Remove the sodium sulfate by gravity filtration and concentrate the filtrate via rotary evaporation to obtain the crude product.</li>
	<li>Purify the crude product via column chromatography on basic alumina using a gradient of 30-50% diethyl ether in hexanes to obtain the pure product as a yellow solid.</li>
</ol>
5. Protection of amine 4 as a tert-butyl carbamate
<ol>
	<li>Dissolve 76 mg of amine 4 in 2 mL of absolute ethanol in a 25 mL round bottom flask under air atmosphere.</li>
	<li>Add 104 mg of di-tert&#173;-butyl dicarbonate followed by 40 mg of solid sodium bicarbonate to the reaction mixture.</li>
	<li>Cap the flask with a rubber septum and sonicate the mixture for 1 h. 
	NOTE: This reaction may be allowed to run overnight.</li>
	<li>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 the bottom of the funnel.</li>
	<li>Transfer the filtrate to a round bottom flask and concentrate on a rotary evaporator. Dissolve the resulting oil in ~2.5 mL of methylene chloride.</li>
	<li>Add ~1.3 g of silica gel to the solution and remove the methylene chloride on the rotary evaporator until a fine, free-flowing solid is obtained.</li>
	<li>Pack the silica gel into a 10 g silica cartridge for automated flash chromatography. 
	NOTE: An automated purification system was used in this protocol. However, conventional flash chromatography with silica gel may also be employed.</li>
	<li>Run the column using a gradient starting from 90:10 hexanes:ethylacetate and ending at 20:80 hexanes:ethyl acetate over a period of 20 min. Collect the fractions containing the product (as indicated by the major peak detected at 254 nm absorbance) in a round bottom flask. Evaporate the hexanes and ethyl acetate on a rotary evaporator to obtain the purified product as a yellow oil.</li>
</ol>
6. Synthesis of tert-butyl (6-oxocyclohepta-2,4-dien-1-yl)(2-phenylethyl) carbamate (6)
<ol>
	<li>In a 10 mL round bottom flask, dissolve 27 mg of iron complex 5 in 1 mL of methanol under air atmosphere and immerse the flask in an ice bath.</li>
	<li>Commence magnetic stirring and add 33 mg of cerium(IV) ammonium nitrate.</li>
	<li>After 30 min, add a second 33 mg portion of cerium(IV) ammonium nitrate, followed by a third 33 mg portion after an additional 30 min of stirring.</li>
	<li>After adding the third portion of cerium(IV) ammonium nitrate, dilute the reaction mixture with ethyl acetate (5 mL).</li>
	<li>Pour the mixture into a 30 mL separatory funnel containing 5 mL of saturated aqueous sodium bicarbonate. Separate the layers.</li>
	<li>Re-extract the aqueous layer with ethyl acetate (2x 5 mL). Dry the combined organic layers over anhydrous sodium sulfate.</li>
	<li>Remove the sodium sulfate via gravity or vacuum filtration and concentrate the filtrate on a rotary evaporator.</li>
	<li>Dissolve the crude product in ~2.5 mL of methylene chloride, add ~1.3 g of silica gel, and remove the solvent on a rotary evaporator.</li>
	<li>Pack the silica gel with the adsorbed crude product into a 10 g silica gel column for automated flash chromatography. 
	NOTE: An automated purification system was used in this protocol. However, conventional flash chromatography with silica gel may also be employed.</li>
	<li>Run the column using a gradient starting from 90:10 hexanes:ethylacetate and ending at 20:80 hexanes:ethyl acetate over a period of 20 min. Collect the fractions containing the product (as indicated by the major peak detected at 254 nm absorbance) in a round bottom flask. Evaporate the hexanes and ethyl acetate on a rotary evaporator to obtain the purified product as a pale brown oil.</li>
</ol>

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<li>Ripoche, I., Gelas, J., Grée, D., Grée, R., Troin, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+new+stereoselective+synthesis+of+chiral+optically+pure+4-piperidones%5BTitle%5D)+AND+%22Tetrahedron+Letters%22%5BJournal%5D)">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/pubmed?term=((Stereoselective+Synthesis+of+2-Dienyl-Substituted+Pyrrolidines+Using+an+%CE%B74-Dienetricarbonyliron+Complex+as+the+Stereodirecting+Element%3A+Elaboration+to+the+Pyrrolizidine+Skeleton%5BTitle%5D)+AND+%22Organic+Letters%22%5BJournal%5D)">Stereoselective Synthesis of 2-Dienyl-Substituted Pyrrolidines Using an η4-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. E., Cividino, P., Court, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthesis+of+Substituted+Cycloheptadienes+by+Catalytic+Hydrogenation+of+Cycloheptatrieneiron+Complexes%5BTitle%5D)+AND+%22Synthetic+Communications%22%5BJournal%5D)">Synthesis of Substituted Cycloheptadienes by Catalytic Hydrogenation of Cycloheptatrieneiron Complexes.</a> Synthetic Communications. 31, 1291-1300 (2001).</li>
</ol>

The authors have nothing to disclose.

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).

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

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

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 η4-diene ligand give rise to the signals at 6.39 ppm (2 H),...

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 ...

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JoVE Journal

Chemistry

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Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

Ruthenium phosphine complexes are widely used for homogeneous catalytic reactions such as hydrogenations. The synthesis of a series of novel tridentate ruthenium complexes bearing the N-triphos ligand N(CH2PPh2)3 is reported. Additionally, the stoichiometric reaction of a dihydride Ru–N-triphos complex with levulinic acid is described.

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

This protocol describes the preparation and characterization of a dendrimeric magnetic resonance imaging (MRI) contrast agent that carries cyclen-based macrocyclic chelates coordinating paramagnetic gadolinium ions. In a series of MRI experiments in vitro, this agent produced an amplified MRI signal when compared to the commercially available monomeric analogue.

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

Here, we describe a protocol for radiolabeling and in vivo testing of tridentate 99mTc(I) chelate-tetrazine derivatives for pre-targeting and bioorthogonal chemistry.

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented. The revised protocol for the synthesis and purification of the ligand minimizes the need for specialized laboratory equipment while simplifying reaction workups and product purification. Use of Cp*H in the synthesis of [Cp*MCl2]2 complexes (M = Ru, Ir) is also described.

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed “Wanzlick dimer” and the reduced stable organic radical.

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

CO2 transformations are conducted in a one-pot two-step procedure for the synthesis of complex molecules. The selective 4 e- reduction of CO2 with a hydroborane reductant affords a reactive and versatile bis(boryl)acetal intermediate which is subsequently involved in condensation reaction or carbene-mediated C-C coupling generation.

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

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Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Learn solvent-free synthesis of aminated tropone derivatives via aza-Michael addition using tricarbonyl(tropone)iron complexes. This efficient method simplifies reaction setup and enables production of structurally complex amines.

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

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