Communication pubs.acs.org/Organometallics
Aerobic Dehydrogenative Heck Reaction of Ferrocene with a Pd(OAc)2/4,5-Diazafluoren-9-one Catalyst Michał Piotrowicz and Janusz Zakrzewski* Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland S Supporting Information *
ABSTRACT: The aerobic dehydrogenative Heck alkenylation of ferrocene with alkenes, catalyzed by a Pd(OAc)2/4,5diazafluoren-9-one system, is disclosed. Monoalkenylated ferrocenes were obtained in moderate yields and selectivities using various electron-poor alkenes. Oxygen at an atmospheric pressure was the sole oxidant. The reaction can be carried out at room temperature (several days) or at 70 °C (∼3 h).
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extremely high reactivity toward electrophiles, estimated as 3.3 × 106 higher than that of benzene in the case of Friedel− Crafts acylation.7 Such a high reactivity constitutes an advantage in the case of C−H activation involving the electrophilic metalation step. It should be emphasized that the synthetic chemistry of ferrocene continues to attract much attention due to the numerous applications of ferrocene derivatives in various branches of science, ranging from materials science to biology and medicine.8 The commercially available and cheap parent ferrocene is a versatile starting material for functionalization, usually via classical reactions with electrophilic reagents. We thought that elaborating novel synthetic methods based on transition-metal-catalyzed C−H activation of ferrocene would result in a simplification of synthetic procedures and in making them more environmentally friendly (the “green” ferrocene chemistry). We started this program with our search for how to accomplish a DHR of ferrocene. In the literature we found only early, brief reports by Fujiwara and Moritani on the alkenylation of this metallocene with various olefins in the presence of stoichiometric amounts of Pd(OAc)2, but these reactions suffered from low yields (24% based on Pd in the best case) and there were no attempts to make them catalytic.9 Moreover, rhodium-catalyzed carbonyl group directed alkenylation of ferrocenyl ketones was also reported.10 In our previous paper6b we disclosed a catalytic direct DHR of ferrocene with α,β-unsaturated esters performed under ambient conditions using air as the sole oxidant. We decided not to use chemical oxidants such as quinones, peroxy compounds, Ag(I) salts, etc. because most of them are known to readily oxidize ferrocene. On the other hand, in
ransition-metal-catalyzed reactions forming C−C bonds via C−H activation represent an atom- and stepeconomical alternative to conventional cross-coupling reactions of organic halides (triflates) and organometallic reagents.1 Among these reactions the Pd(II)-catalyzed dehydrogenative coupling of arenes and alkenes (the dehydrogenative Heck reaction (DHR), also known as the Fujiwara−Moritani (F-M) reaction) is of particular interest because it provides a straightforward route to compounds having conjugated arene−alkene π systems which may exhibit interesting physicochemical properties and biological activity and may serve as useful synthetic building blocks.2 In the vast majority of examples DHRs are catalyzed by Pd(OAc)2 alone (“ligandless” DHRs) and require an oxidant for reoxidation of Pd(0) formed in the catalytic cycle to active Pd(II) species. For obvious reasons considerable effort has been focused on aerobic F-M reactions using molecular oxygen (air) as the sole oxidant, but unfortunately, direct reoxidation of Pd(0) by O2 alone is often inefficient.3 Nevertheless, some aerobic DHRs have been reported to date.4 Another challenging problem in DHRs is how to perform them without heating (at room temperature). Here, again, successful examples are scarce.4e,5 The substrate scope of DHRs is relatively wide and encompasses a variety of arenes, heteroarenes, and olefins (although electron-deficient olefins such as acrylates were the most frequently used). The arene was frequently a benzene derivative possessing directing groups facilitating C−H activation and ensuring site selectivity via precoordination of the catalyst. C−H bond activation of simple arenes which do not possess directing groups (undirected C−H activation) is still challenging due to lower reactivity and difficulty in controlling selectivity.1b Continuing our longstanding interest in the chemistry of ferrocene,6 we decided to check whether the methods of transition-metal-catalyzed C−H bond functionalization can be applied to this aromatic metallocene. Ferrocene exhibits © XXXX American Chemical Society
Special Issue: Ferrocene - Beauty and Function Received: May 10, 2013
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dx.doi.org/10.1021/om400410u | Organometallics XXXX, XXX, XXX−XXX
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contrast to Pd(0), which is slowly oxidized to Pd(II) by oxygen (air), ferrocene is practically air-stable.11 We found that ferrocene slowly reacts with α,β-unsaturated esters (for several days) at ambient temperature, but attempts to perform this reaction at a higher temperature (70 °C) resulted only in fast precipitation of inactive Pd black. We hypothesized that this may be due to a reduced solubility of air (oxygen) in the reaction medium at a higher temperature, hampering efficient reoxidation of Pd(0). Surprisingly, the reaction afforded not only monoalkenylated but also all isomeric bis-alkenylated ferrocenes, which were formed even at a ferrocene to ester ratio of 2:1 (Scheme 1).
Scheme 2. Pd(OAc)2/DAF-Catalyzed Aerobic DHR of Ferrocene with MVK
Table 1. Optimization of the DHR of Ferrocene with MVK Catalyzed by Pd(OAc)2 (5 mol %) and DAF entry
Scheme 1. Room-Temperature DHR of Ferrocene with α,βUnsaturated Esters6b
1 b
2 3 4 5 6 7
8 9 10 11 12 13c 14 15d
Herein we report that addition of some nitrogen ligands such as 4,5-diazafluorene and its derivatives and even simple pyridines to our catalytic system markedly improves its efficiency, stability, and selectivity, thus enabling clean ferrocene monoalkenylation at room temperature (the reaction time is several days) or at a higher temperature (70 °C) in a shorter period of time (∼3 h). The most efficient ligand was 4,5-diazafluoren-9-one (DAF; Chart 1), recently used in some Pd(II)-catalyzed dehydrogenation reactions and allylic C−H acetoxylation.12 The substrate scope of this reaction was also studied using various olefins.
t (°C) room temp room temp room temp room temp room temp room temp room temp 70 70 70 70 70 70 70 70
DAF (mol %)
time
FcH conversion (%)
yield of 1aa (%)
5
3 days
14
11
5
3 days
21
15
5
7 days
47
46
5
10 days
54
40
5
14 days
61
37
10
7 days
72
57
2
7 days
13
7
0 5 5 5 5 5 10 5
3h 1.5 h 3h 5h 24 h 3h 3h 3h
41 64 74 76 100 49 67 78
33 56 65 61 18 42 51 14
a
Isolated yields. bReaction performed at 10 atm of O2. cAir (1 atm) used instead of O2. dReaction performed in the presence of 1 equiv of t-BuOOH.
silica gel column chromatography. An increase in oxygen pressure to 10 atm did not significantly improve the conversion and yield (entry 2 versus entry 1). The best yields of 1a (46− 57%) were observed after 7 days. In the presence of 5 mol % of the catalyst, 1a was formed in 46% yield with 98% selectivity (entry 3). A higher catalyst loading (10 mol %) increased the yield of 1a to 57% but lowered the selectivity to 78% (entry 6). In this case we observed the formation of more polar products, presumably mixtures of dialkenylated ferrocenes, as reported earlier for the reaction of ferrocene with ethyl acrylate. However, in this work we did not try to separate and characterize these byproducts. Longer reaction times brought about a higher ferrocene conversion, but the yields of 1a decreased. This may suggest a subsequent transformation of 1a into bis-alkenylated products, as observed earlier for the reaction with ethyl acrylate. Next we studied the same reaction at 70 °C. In this case the reaction carried out in the absence of DAF, despite considerable precipitation of Pd black, afforded, in 3 h, 1a in 33% yield at a ferrocene conversion of 44% (entry 8). The addition of DAF resulted in an almost 2-fold increase in the yield of 1a (65% at a ferrocene conversion of 74%, selectivity 88%, no precipitation of Pd black, entry 10). The replacement of O2 by air brings about a ∼1.5-fold decrease in the ferrocene conversion and yield (entry 9).
Chart 1. Chemical Structure of DAF
We studied the catalytic efficiency of the Pd(OAc)2/DAF system in the DHR of ferrocene with methyl vinyl ketone (MVK) carried out at room temperature and at 70 °C (Scheme 2). Most experiments were performed under O2 at atmospheric pressure using Pd(OAc)2 (5 mol %) as a catalyst, but for comparison, some experiments were also done under higher pressure, in air, and at different catalyst loadings. The results obtained are gathered in Table 1 and in the Supporting Information. The reaction of ferrocene with MVK catalyzed by Pd(OAc)2/DAF proceeds slowly at room temperature (entries 1−7). We were unable to obtain complete conversion of ferrocene, but its separation from 1a is very easy when using B
dx.doi.org/10.1021/om400410u | Organometallics XXXX, XXX, XXX−XXX
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It is evident from the above data that the catalytic system Pd(OAc)2/DAF in the investigated DHR is more efficient and selective than Pd(OAc)2 alone (compare entries 8 and 10 and the results obtained in our previous work6b). A striking feature of the reaction under study is its relatively high selectivity for monosubstitution observed up to a ferrocene conversion of around 50% and its sharp decrease at higher conversions (see the Supporting Information). Apparently, the decomposition processes seem to have an induction period before starting, but unfortunately, we are not able to explain this phenomenon in more detail. Having optimized the conditions for the reaction carried out in the presence of DAF, we next performed a screening of some ligands containing the 4,5-diazafluorene skeleton as well as some other structurally related nitrogen ligands (see the Supporting Information). We have found that ligands having a 4,5-diazafluorenone skeleton display higher catalytic activity than structurally similar bipyridine and phenanthroline ligands. This difference in catalytic activity may be explained by the different ligand properties of these compounds. It is well established that DAF forms complexes with longer (weaker) metal−nitrogen bonds than do bipyridine and phenanthroline.13 Such complexes may be less stable and therefore more active catalytically. Surprisingly, substituents at C-9 in 4,5-diazafluorene exert only a weak influence on the ligand catalytic activity. Nevertheless, the commercial DAF proved to be the most active ligand in this series. In the literature there are several reports on the use of pyridine-type ligands in DHRs.14 In most cases basic pyridines strongly binding to Pd inhibit the catalytic turnover, whereas more weakly coordinating pyridines with reduced basicity and/ or steric hindrance around the nitrogen may cause the opposite effect. Furthermore, the effect of the pyridine ligand depends on the oxidant used.14a In the catalytic system under study we observed modest catalytic activity of pyridine-type ligands. However, these ligands did not sufficiently stabilize the active Pd species during the reaction and we observed partial precipitation of Pd black. We next examined the substrate scope of the reaction using DAF as a ligand (Scheme 3). We found that a variety of olefins containing electron-withdrawing groups such as ketone, aldehyde, ester, and phosphonate afforded monoalkenylated ferrocenes in acceptable yields. Olefins having phenyl rings at C-2 generally gave lower yields than olefins that were not substituted at this position. Furthermore, olefins which did not contain electron-withdrawing groups or had electron-donating groups, e.g. styrene and butyl vinyl ether, gave only trace amounts of the coupling products. In all cases the reaction was entirely stereoselective, yielding E isomers. This has been deduced from the large values (15.6− 16.2 Hz) of coupling constants between olefinic protons for compounds 1a−e and from the NOESY correlation between the olefinic and ferrocenyl protons for compounds 1f−i. We believe that the reported reaction proceeds via a mechanism generally accepted for DHRs2 and recently confirmed by theoretical calculations15 involving arene C−H activation via concerted metalation/deprotonation as the ratedetermining step followed by syn insertion of the olefin into the Pd−C bond, syn elimination of a palladium hydride leading to the coupling product, and the formation of Pd(0), which is reoxidized to Pd(II) to sustain the catalytic turnover.
Scheme 3. Aerobic DHR of Ferrocene with Various Alkenes
This mechanism is in line with the measured (using ferrocene-d1016) kinetic isotopic effect (KIE) of deuterium. In a competitive “one-vessel” reaction performed at 70 °C, we obtained KIE = 3.0 ± 0.2. Furthermore, the reaction of ferrocene-d10 with MVK performed at 70 °C in the presence of 5% Pd-DAF for 1 h afforded 1a-d9 in 12% yield at a ferrocene conversion of 17%, whereas under the same conditions ferrocene afforded 1a in 35% yield at a ferrocene conversion of 39%. This result also suggests KIE ≈ 3. Therefore, the KIE values confirm C−H activation as a rate-determining step in the reaction under study.17 We also have evidence for the syn elimination of a palladium hydride step, which is provided by the fact that coumarin did not react with ferrocene under the conditions described above. In fact, the rigid cyclic structure of this compound renders this step impossible from the product of a syn insertion of “Fc-PdAc” (Figure 1).
Figure 1. Intermediate formed by the syn insertion of coumarin into Fc-Pd(OAc). C
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Finally, we did not observe the formation of a ferrocenium cation in the course of the investigated reaction. This ion’s involvement in the reaction mechanism seems unlikely, because the addition of 1 equiv of t-BuOOH, which should facilitate ferrocene oxidation, had a negligible effect on the ferrocene conversion and a detrimental effect on the yield of 1a (Table 1, entry 15). In conclusion, we have elaborated an efficient atom- and step-economical method of alkenylation of ferrocene with alkenes containing electron-withdrawing groups. Our results, along with those obtained recently for directed ferrocene C−H alkenylation,10 amidation,18 arylation,19 and annulation20 and nondirected arylation21 and borylation22 reveal the potential of methods based on catalytic C−H activation in ferrocene functionalization. It is also worth noting that our system uses molecular oxygen as the sole oxidant and, therefore, is much simpler than systems using co-oxidants and electron-transfer mediators.
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ASSOCIATED CONTENT
S Supporting Information *
Figures and text giving details of the syntheses and characterization data. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail for J.Z.:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Financial support from the Faculty of Chemistry, University of Łódź, is gratefully acknowledged. REFERENCES
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