Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Summary
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.
Abstract
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 ºC for 16 h. With the optimized catalytic conditions in hand, representative α– and/or β-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.
Introduction
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'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 α-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.
Protocol
Representative Results
Discussion
[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 α-subst…
Disclosures
The authors have nothing to disclose.
Acknowledgements
The authors have nothing to disclose.
Materials
| Allyl Acetate | TCI | A0020 | > 98.0%(GC), 25 mL package |
| Dichloro(p-cymene)ruthenium(II) dimer | TCI | D2751 | > 95.0%(T), 5 g package |
| Silver hexafluoroantimonate | TCI | S0463 | > 97.0%(T), 5 g package |
| 1,2-Dichloroethane | TCI | D0364 | > 99.5%(GC), 500 g package |
| Rotavapor | EYELA | N-1200A | Use to dry solvent |
| Silica gel | Merck | 107734 | Silica gel 60 (0.063-0.2 mm), for column chromatoraphy |
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