Name: facile preparation of (2z,4e)-dienamides by the olefination of electron-deficient alkenes with allyl acetate
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Caution: Please consult all relevant material safety data sheets (MSDS) before use. All cross-coupling reactions should be performed in vials under a sealed argon atmosphere (1 atm).
1. Preparation of Butadienes by the Olefination of Acrylamides with Allyl Acetate
<ol>
	<li>Dry a screw-cap vial (8 mL) with a compatible magnetic stir bar in an oven at 120 &#176;C for over 2 h. Cool the hot vial to room temperature by blowing on it with inert gas before use.</li>
	<li>Use an analytical balance...

<ol>
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[Ru(p-cymene)Cl2]2 is a cheap, easily accessible, air-stable, and highly active Ru-based catalyst with excellent functional group tolerance that efficiently operates under mild reaction conditions to give C-H/C-H coupling butadiene products. Silver salt AgSbF6 was used as an additive that may abstract the chloride of [Ru(p-cymene)Cl2]2 to generate a cationic ruthenium complex for the following C-H bond activation. However, only &#945;-subst...

Butadienes are widely occurring and are commonly found in many natural products, drugs, and bioactive molecules1. Chemists have made intense efforts to develop an efficient, selective, and practical synthetic methodology for the synthesis of 1,3-butadienes2,3. Recently, direct cross-couplings between two alkenes via double vinylic C-H bond activation was developed, representing an efficient strategy for the synthesis of butadienes, with high atomic and step economy. Among them, the palladium-catalyzed cross-coupling of two alkenes has attracted much attention, providing (E,E)-configured butadienes via alkenyl-Pd species4,5. For example, Liu&#39;s group developed a Pd-catalyzed butadiene synthesis by the direct cross-coupling of alkenes and allyl acetate (Figure 1 and Equation 3)4. Meanwhile, the functional group-directed cross-coupling between alkenes provided butadienes with excellent (Z,E)-stereoselectivity due to the olefinic C-H cyclometalation event, representing a complementary method6. To date, some directing groups, such as enolates, amides, esters, and phosphates, have been successfully introduced to the cross-coupling between alkenes, providing a series of valuable and functionalized 1,3-butadienes. However, the directed cross-coupling reaction has not been developed, as there are still limited directing groups in practical use. In particular, a stoichiometric amount of oxidant is usually required to maintain the catalytic cycle, which produces a large amount of organic and inorganic wastes. There are very limited examples using electron-rich alkenes as the coupling partner.
Allyl acetate and its derivatives have been deeply investigated in organic transformations as powerful allylation and olefination reagents, including catalyzed cross-coupling, Friedel-Crafts allylation of electron-rich arenes, and catalytic C-H activation of electron-deficient arenes (Figure 1 and Equation 1)7. More recently, the Loh group developed a rhodium(III)-catalyzed C-H allylation of electron-deficient alkenes with allyl acetates, creating 1,4-dienes (Figure 1 and Equation 2)8. Meanwhile, the Kanai group reported a dehydrative direct C-H allylation with allylic alcohols by using a Co(III) catalyst9. Interestingly, Snaddon and co-workers disclosed a novel cooperative catalysis-based method for the direct asymmetric &#945;-allylation of acyclic esters10. Very recently, the Ackermann group reported several novel allylation examples using inexpensive Fe, Co, and Mn catalysts11. These reports have made breakthroughs in allylation and olefination reactions, but double-bond migration and poor regioselectivity are usually inevitable and are not easily controlled. Hence, developing more efficient and selective reaction patterns of allyl acetates to construct valuable molecules is still highly desirable. With our interest in novel 1,3-butadiene synthesis via C-H olefination, we assumed that allyl acetate could be introduced to the directed allylation of electron-deficient alkenes, first delivering 1,4-diene. Then, the more thermodynamically stable 1,3-butadiene could be formed after the migratory isomerization of the C-C double bond7, forming the diene product that cannot be obtained by cross-coupling using electron-rich alkenes, such as propene, as coupling partner6. Here, we report an inexpensive Ru(III)-catalyzed olefinic C-H bond olefination of acrylamides with allyl acetates in the absence of any oxidant, which opens a novel synthetic route for the creation of (Z,E)-butadienes (Figure 1 and Equation 4)13.

<table border="0" cellpadding="0" cellspacing="0" width="887">
	<tbody>
		<tr height="19">
			<td height="19" style="height:19px;width:284px;">Allyl Acetate</td>
			<td style="width:100px;">TCI</td>
			<td style="width:148px;">A0020</td>
			<td style="width:355px;">&#62; 98.0%(GC), 25 mL package</td>
		</tr>
		<tr height="38">
			<td height="38" style="height:38px;width:284px;">Dichloro(p-cymene)ruthenium(II) dimer</td>
			<td style="width:100px;">TCI</td>
			<td style="width:148px;">D2751</td>
			<td>&#62; 95.0%(T), 5 g package</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Silver hexafluoroantimonate</td>
			<td style="width:100px;">TCI</td>
			<td style="width:148px;">S0463</td>
			<td>&#62; 97.0%(T),&#160; 5 g package</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">1,2-Dichloroethane</td>
			<td style="width:100px;">TCI</td>
			<td style="width:148px;">D0364</td>
			<td>&#62; 99.5%(GC), 500 g package</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Rotavapor</td>
			<td style="width:100px;">EYELA</td>
			<td style="width:148px;">N-1200A</td>
			<td>Use to dry solvent</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:284px;">Silica gel</td>
			<td style="width:100px;">Merck</td>
			<td style="width:148px;">107734</td>
			<td>Silica gel 60 (0.063-0.2 mm), for column chromatoraphy</td>
		</tr>
	</tbody>
</table>

facile preparation of (2z,4e)-dienamides by the olefination of electron-deficient alkenes with allyl acetate

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high atomic and step economy. However, this functionality-directed cross-coupling reaction has not been developed, as there are still limited directing groups in practical use. In particular, a stoichiometric amount of oxidant is usually required, producing a large amount of waste. Due to our interest in novel 1,3-butadiene synthesis, we describe the ruthenium-catalyzed olefination of electron-deficient alkenes using allyl acetate and without external oxidant. The reaction of 2-phenyl acrylamide and allyl acetate was chosen as a model reaction, and the desired diene product was obtained in 80% isolated yield with good stereoselectivity (Z,E/Z,Z = 88:12) under optimal conditions: [Ru(p-cymene) Cl2]2 (3 mol %) and AgSbF6 (20 mol %) in DCE at 110 &#186;C for 16 h. With the optimized catalytic conditions in hand, representative &#945;- and/or &#946;-substituted acrylamides were investigated, and all reacted smoothly, regardless of aliphatic or aromatic groups. Also, differently N-substituted acrylamides have proven to be good substrates. Moreover, we examined the reactivity of different allyl derivatives, suggesting that the chelation of acetate oxygen to the metal is crucial for the catalytic process. Deuterium-labeled experiments were also conducted to investigate the reaction mechanism. Only Z-selective H/D exchanges on acrylamide were observed, indicating a reversible cyclometalation event. In addition, a kinetic isotope effect (KIE) of 3.2 was observed in the intermolecular isotopic study, suggesting that the olefinic C-H metalation step is probably involved in the rate-determining step.

Our efforts were focused on the preparation of 1,3-butadiene from acrylamide and allyl acetate.
Table 1 illustrates the optimization of conditions, including the screening of various additives and solvents, using [Ru(p-cymene)Cl2]2 as the catalyst. After screening a series of representative solvents, we were pleased to find that the product yield dramatically improved to 80%, with ...

Watch this Scientific Journal Video about Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate at JoVE.com

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

The ruthenium-catalyzed olefination of electron-deficient alkenes with allyl acetate is described here. By using aminocarbonyl as a directing group, this external oxidant-free protocol has high efficiency and good stereo- and regioselectivity, opening a novel synthetic route to (Z,E)-butadiene skeletons.

Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high ...

The overall goal of this ruthenium catalyzed and oxidant free protocol is to synthesize Z, E-butadienes by olefination of electron-deficient alkenes using aminocarbonyl as a directing group. This method that can help answer key questions in a C-H bound functionalization, such as the olifination of alkenes using allyl acetate. The main advantage of this technique is that Z, E-butadiene can be obtained directly from acrylic amide and allyl acetate result in antioxidant using inexpensive ruthenium in catalyst.Demonstrating the procedure will be Chunbing Yu, a graduate student in our laboratory;Prior to starting this procedure, dry an eight milliliter screw cap reaction vial with a compatible magnetic stir bar in an oven at 120 degrees Celsius for over two hours. After removing the vial from the oven, cool it to room temperature with inert gas before use. Using an analytical balance, weigh 3.7 milligrams of ruthenium cyme chloride dimer and 13.7 milligrams of silver hexafluoroantimonate into the reaction vial.Next, add one milliliter of dry 1, 2-dicholoroethane to the reaction viae. Using the analytical balance, weigh 0.2 millimoles of acrylamide into the reaction vial. Then, add 43 microliters of allyl acetate to the reaction vial with a micro syringe.Following this, blanket the reaction vial with argon and immediately cover it with a compatible screw cap. Stir the reaction mixture at room temperature for five minutes. Then heat the reaction mixture to 110 degrees Celsius in an oil bath with stirring for 16 to 18 hours.After cooling the vial down, use thin layer chromatography or TLC, to monitor the progress of the reaction by comparing the reaction mixture to an acrylamide standard. Use a 1:2 ratio of ethyl acetate and petroleum ether to develop the TLC plate. Now dissolve the crude product in a minimum volume of dichloromethane and load it onto a silica gel column wet with petroleum ether.Separate the cross coupling products by column chromatography, using a mixture of ethyl acetate and petroleum ether as the eluent. After connecting the eluent containing product in a flask, evaporate the solvent on a rotary evaporator. Then place the flask under a high vacuum for a minimum of two hours to obtain 20 to 50 milligrams of product for characterization by NMR spectroscopy.The optimization of conditions for the preparation of 1, 3-butadiene, including the screening of various additives and solvents, using your ruthenium cymene chloride dimer as the catalyst is shown here. The scope of the reaction was explored by submitting various acrylamides to the optimized conditions in the presence of allyl acetate 2a. Modest to excellent yields were obtained with good ratio selectivity and alkene selectivity.The reactivity of different allyl derivatives and branched allyl acetates, was also examined. Alpha and beta substituted allyl acetates were completely inert for cross coupling. While gamma substituted allyl acetate afforded only trace product.Other allyl carboxylic esters showed decreased reactivity compared to allyl acetate 2a. And allyl methyl carbonate 2f was more inactive, forming product in 24%yield. To investigate the reaction mechanism, two deuterium labeled experiments were conducted.When acrylamide 1g was subjected to a standard catalytic system in the presence of acetic acid D4, the cationic ruthenium species led to a Z selective hydrogen deuterium exchange on a acrylamide, indicating a reversible cyclometalation event. Moreover, a kinetic isotope effect of 3.2 was observed in the intermolecular isotopic study, suggesting that the olefinic carbon-hydrogen bond metalation step, is probably involved in the rate determining step.

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