Abstract
An unprecedented application of aryliodine (III) diacetates as substrates in Pd-Ag catalyzed arylation of alkenes is described. The mechanistic studies revealed that the binary Pd-Ag catalysis leads to the decomposition of aryliodine (III) diacetates to oxygen and aryl iodides followed by arylation of alkenes forming Heck-type products. Under optimized conditions both electron-rich and electron-deficient alkenes undergo arylation in high yields. Advantageously, the reaction proceeds smoothly in water as a solvent and neither organic ligands nor inert atmosphere are required.
Keywords: Synthesis in Water, Palladium, Cross-coupling, Hypervalent Iodine
The arylation of alkenes using Heck-type transformations is an important method in organic synthesis.1 The exploration of the scope of this process has revealed a number of possible leaving groups that can be utilized in the aryl electrophile coupling partner (Scheme 1).1,2
Scheme 1.
Reactions formally involving the use of “H” as a leaving group, so-called dehydrogenative or oxidative Heck transformations, involve Pd(II) catalysis and require an oxidant to regenerate the active Pd(II) species.2d,e The successful oxidizing agents utilized in this process include Cu or Ag salts, benzoquinone, oxygen and peroxides.2e Interestingly, ArI(OAc)2 reagents, widely used in many palladium-catalyzed oxidative transformations,3,4 fail in Heck-type reactions because of their propensity to oxidize olefins3,5 and we are unaware of a single example of such chemistry. Herein, we report that such an attempt to use ArI(OAc)2 reagents in an oxidative Heck process resulted in an unprecedented reaction of ArI(OAc)2 with alkenes under Pd-Ag binary catalysis (Scheme 2). This finding expands the scope of Heck chemistry by including the formal “I(OAc)2” leaving group to the existing arsenal of Heck nucleofuges.
Scheme 2.
When this project was started, a direct arylation of allyl acetate through the functionalization of an aromatic C-H bond was unknown.6 In an attempt to accomplish such a transformation, we used PhI(OAc)2 as an oxidizing agent and electron-rich 2,4-dimethoxybenzene to facilitate the oxidative electrophilic palladination of an aromatic C-H bond. In addition, we added one half equivalent of silver carbonate, whose proposed function was to stabilize the intermediate aryl-cationic Pd-complex1,7 and to scavenge acetate ions produced during PhI(OAc)2 reduction. Surprisingly, instead of the expected dimethoxycinnamyl acetate we isolated only unsubstituted cinnamyl acetate (3a) in 68% (Scheme 3).
Scheme 3.
Clearly, allyl acetate underwent cross-coupling with PhI(OAc)28 and not dimethoxybenzene. A search of the literature revealed that this was a new transformation, presumably missed by the previous investigators because ArI(OAc)2 is not commonly employed as an oxidazing agent in these oxidative Heck transformations. Furthermore, it is known that under acidic conditions PhI(OAc)2 reacts with arenes and olefins under Pd catalysis to give acetoxyarenes9 and vicinal diacetyldiols,10 respectively. Neither was detected in our experiment conducted under basic conditions. Our optimization experiments are shown Table 1.
Table 1. Optimization of Coupling of ArI(OAc)2 with Allyl Acetate.
 | |||||||
|---|---|---|---|---|---|---|---|
| entry |
1a equiv. |
2a equiv. |
Pd equiv. |
Ag2CO3 equiv. |
TEMPO equiv. |
equiv. of base | yield, (%)a |
| 1 | 1 | 1 | 0.05 | 1 | 0 | none | 50 |
| 2 | 1.1 | 1 | 0.05 | 1 | 0 | none | 52 |
| 3 | 1.1 | 1 | 0.05 | 1 | 0.1 | none | 64 |
| 4 | 1.1 | 1 | 0.05 | 1 | 0.2 | none | 58 |
| 5 | 1.1 | 1 | 0.05 | 1 | 0.1 | 0.5 of K2CO3 | 22 |
| 6 | 1.1 | 1 | 0.05 | 1 | 0.1 | 0.5 of Cs2CO3 | 2 |
| 7 | 1.1 | 1 | 0.05 | 1 | 0.1 | 0.5 of CaCO3 | 88 |
| 8 | 1.1 | 1 | 0.05 | 0 | 0.1 | 0.5 of CaCO3 | 3 |
| 9 | 1.1 | 1 | 0.05 | 0.1 | 0.1 | 0.5 of CaCO3 | 28 |
| 10 | 1.1 | 1 | 0.05 | 0.5 | 0.1 | 0.5 of CaCO3 | 87 |
| 11 | 1.1 | 1 | 0 | 0.5 | 0.1 | 0.5 of CaCO3 | 0 |
| 12 | 1.1 | 1 | 0.01 | 0.5 | 0.1 | 0.5 of CaCO3 | 5 |
| 13 | 1.1 | 1 | 0.03 | 0.5 | 0.1 | 0.5 of CaCO3 | 82 |
| 14b | 1.1 | 1 | 0.03 | 0.5 | 0.1 | 0.5 of CaCO3 | 80 |
Isolated by column chromatography.
Water was used as a solvent
It was found (Table 1) that the reaction critically requires both Pd and Ag catalysts; if either is omitted no product is obtained. (entries 8, 11). In addition, base is important for the coupling, indeed the highest yields were obtained with 0.5 equiv. of CaCO3 (entries 7, 10, 13, 14). Also, using TEMPO we were able to improve the product yield (entries 2, 3). The precise role of TEMPO is not clear at this point, however, this reagent was reported to improve reaction yields in oxidations of allylic alcohols to unsaturated aldehydes by PhI(OAc)23 and in general is known to facilitate various redox processes.11 Pleasingly, the reaction also proceeded in high yield when water was used as a solvent (entry 14).
The effects of electron properties of alkenes were explored next (Table 2). The reactions of electron-deficient alkenes required 10 mol% excess of the alkene and no TEMPO (entry 5), whereas the behavior of styrene was similar to that of allyl acetate, requiring 10 mol% of TEMPO (entry 9). In addition, the reaction was successful with 4-methoxyphenyliodine (III) diacetate12 (entry 10-12) giving excellent product yields.
Table 2. Optimization of Coupling of ArI(OAc)2 with Alkenes.
 | ||||||
|---|---|---|---|---|---|---|
| entry |
1 (equiv.) |
2 (equiv.) |
Pd (equiv.) |
TEMPO (equiv.) |
product | yield, (%)a |
| 1 | 1.1 | 1 | 0.05 | 0.1 | 3b | 68 |
| 2 | 1 | 1.1 | 0.05 | 0.1 | 3b | 75 |
| 3 | 1 | 1.1 | 0.03 | 0.1 | 3b | 72 |
| 4 | 1 | 1.1 | 0.03 | 0 | 3b | 71 |
| 5 | 1 | 1.1 | 0.05 | 0 | 3b | 85 |
| 6 | 1 | 1.1 | 0.05 | 0 | 3c | 69 |
| 7 | 1.1 | 1.1 | 0.03 | 0 | 3c | 31 |
| 8 | 1.1 | 1 | 0.03 | 0.1 | 3c | 73 |
| 9 | 1.1 | 1 | 0.05 | 0.1 | 3c | 88 |
| 10 | 1.1 | 1 | 0.05 | 0.1 | 3d | 89 |
| 11 | 1 | 1.1 | 0.05 | 0.1 | 3e | 87 |
| 12 | 1.1 | 1 | 0.05 | 0 | 3f | 91 |
Isolated by column chromatography.
Sanford13a,b and Ritter13c have shown that ArI(OAc)2 are substrates for Pd(II) oxidative insertion into I-O bond, forming Pd(IV) or Pd(III) bimetallic species and aryliodide as a side product. Thus, we studied the conversion of 4-methoxyphenyliodine (III) diacetate into iodoanisole (Table 3). Indeed, we found that such decomposition14 is fastest when all our reaction components are present (entry 7).
Table 3. Decomposition of 4-Methoxyphenyl (III) Diacetate to Iodoanisole.
 | |||
|---|---|---|---|
| entry | catalyst | % of iodoanisolea | time for the full conversion, (hours)b |
| 1 | none | 16 | 78 |
| 2 | CaCO3 | 50 | 60 |
| 3 | Ag2CO3 | 57 | 48 |
| 4 | Pd(OAc)2 | 86 | 15 |
| 5 | Pd(OAc)2 + CaCO3 | 90 | 13 |
| 6 | Pd(OAc)2 + Ag2CO3 | 93 | 12 |
| 7 | Pd(OAc)2 + CaCO3 + Ag2CO3 | 100 | 5 |
After 8 hours, monitored by NMR.
Reactions conducted in sealed NMR tubes.
Additionally, we subjected this cross-coupling reaction (Table 1) to a thorough analysis by HPLC-MS and GC-MS. Trans-cinnamyl acetate was detected as a major product along with the traces of 3-phenylpropanaldehyde (product of β‘-hydride elimination), phenyl iodide (decomposition product), and cis-cinnamyl acetate. These findings prompted us to propose a plausible mechanism for the reaction (Scheme 4).
Scheme 4.
The evolution of oxygen in stoichiometric quantities was confirmed by the indigo carmine and sodium dithionite methods.15 It is well known that aryliodine (III) compounds can be obtained by oxidation of aryliodides with peroxy acids.12 Thus, the reverse process involves decomposition of ArI(OAc)2 and generation of AcOOAc and ArI. It is feasible that Pd catalyzes this reaction through the formation of an unstable PdX2(OAc)2. Under basic conditions AcOOAc undergoes Ag-catalyzed decomposition with the production of O2. The in-situ formed aryl iodide reacts with the alkene under these conditions as has been reported previously16 and shown in a control experiment, in which 0.5 equiv. of each PhI(OAc)2 and 4-methoxyiodoanisole were used giving the equal amounts of the respective cinnamyl acetates (Scheme 5).
Scheme 5.
In summary, we discovered a new alkene arylation reaction with ArI(OAc)2. Since oxidative alkene arylations are commonly achieved with diaryliodonium salts, which are in turn prepared17 from ArI(OAc)2, our process is synthetically more convenient. This reaction does not involve the use of organic ligands or inert atmosphere and can be performed in water as a solvent. Because of the high yields, the purification of the products is advantageously simple and consists only of a short silica gel pad to separate inorganic salts.18
Acknowledgment
This work is supported by the US National Institute of Health (grants RR-16480 and CA-135579) under the BRIN/INBRE and AREA programs. Collaboration with Mass Spectroscopy Facility at University of New Mexico is acknowledged. In addition, we thank the reviewer of this manuscript for suggesting the experiment shown in Scheme 5.
Footnotes
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References and notes
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