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Ultrasound Chemistry Highlights

Thursday, June 25, 2009
Ricardo A. W. Neves Filho
Universidade Federal de Pernambuco

Part 1: Ultrasound-promoted palladium-catalyzed cross coupling reactions

Ultrasound-Promoted Heck Reaction in Room Temperature Ionic Liquids

In 2001, Srinivasan and co-workers form National Chemical Laboratory, Pune, described the first Heck reaction performed in ionic liquids (IL) under ultrasound irradiation. In their article, many aryl iodides were coupled with activated alkenes with remarkable results in terms of yields, reaction time and selectivity. (Chem. Commun. 2001, 1544. DOI: 10.1039/b104532f) This new synthetic methodology is quite superior to conventional Heck reactions, which are generally carried out in polar solvents such as DMF and NMP under reflux conditions with long reaction times. In this reaction, the sound wave activation was found to be essential because no conversion of the starting materials took place when it was repeated under conventional stirring. Furthermore, in some cases, conventional Heck alkenylations lead to the formation of mixtures of E/Z diastereoisomers; nevertheless, the ultrasound-mediated protocol furnished exclusively the E products. It is noteworthy that phenylacetylene also undergoes the reaction; thus, this procedure can be used as an alternative to the Sonogashira reaction. It is also important to mention that the ultrasound-mediated Heck reaction does not need the use of phosphine ligands to stabilize the Pd(0) catalyst. Indeed, the reaction of the Pd(II) salt with ionic liquid leads to the formation of a Pd-carbene complex with alkylimidazol-2-ylidene. This complex is then reduced sonochemically in situ by a single electron transfer (SET) process, to afford a Pd(0) species that is the active catalyst for the Heck reaction.

Ultrasound-Promoted Suzuki Reaction in Room Temperature Ionic Liquid

The same group of Indian researchers cited above disclosed the first Suzuki reaction performed in ionic liquids with ultrasound activation. (Chem. Commun. 2002, 616. DOI: 10.1039/b111271f) The reactions between phenylboronic acid and aryl halides have been carried out employing [bbim]+[BF4]- / MeOH as solvent system. In their work, the Suzuki reaction was first investigated employing Pd(OAc)2 as catalyst, in the absence of phosphine ligands. Under these conditions a series of 11 biaryls were synthesized in good yields and short reaction times. The reaction has presented a good scope of applications, since aryl halides containing electron-donating groups (EDG) reacted as well as the ones containing electron-withdrawing groups (EWG). It is also important to note that even chlorobenzenes undergo the Suzuki reaction to afford biaryls in 42-65% yields. Although yields for these latter conversions were moderate, chlorobenzenes are known to have poor reactivity under Suzuki conditions. Thus, this acoustic technique is quite valuable for coupling these substrates with boronic acids. In the same paper, the authors improved the reaction by employing tetrafluoroborate bis-butylimidazol-2-ylidene-palladium (II) carbene complex A instead of Pd(OAc)2. This modification has allowed them to recycle and re-use the palladium catalyst without losses in terms of yields and reaction times.

Ultrasound-Assisted Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by Pd/PVP

The group of Antunes from Federal University of Rio de Janeiro has developed a new protocol for Suzuki cross coupling reaction catalyzed by palladium nanoparticles stabilized in poly(vinylpyrrolidone) (PVP). The new method for the Suzuki reaction was investigated under conventional or microwave heating (MW) as well as ultrasound irradiation (US). (Tetrahedron Lett. 2008, 49, 3895. DOI: 10.1016/j.tetlet.2008.04.061) The reaction presented a large range of applications, since aryl iodides or bromides containing EDG or EWG reacted with arylboronic acids to furnish biaryls in good yields. Although the best results have been achieved when using dielectric heating (MW), ultrasound irradiation was also attractive when compared with conventional heating. In the experiments performed under conventional heating, coupled products have been obtained in good yields after 18 h of reaction time while using sound wave activation; similar results have been obtained in just 5 h of reaction. In addition, the catalyst could be recycled and re-used two times without loss in yield.

Ultrasound-Assisted cross-coupling reaction between potassium trifluoroborate salts and organotellurides

Hélio A. Stafani and Rodrigo Cella from the University of São Paulo, Brazil, have reported a new method for preparation of Z- or E-stilbenes by the ultrasound-assisted cross-coupling reaction between potassium trifluoroborate salts and aryl- or vinyltellurides. (Tetrahedron 2006, 62, 5656. DOI: 10.1016/j.tet.2006.03.090) The reaction has been employed to synthesize a series of 22 alkenes with defined stereochemistry, giving good yields in 40 min. For comparison proposes, the reaction was carried out under magnetic stirring and it was observed that much of the starting material remained unchanged after 24 h of reaction. After repeating the same reaction under reflux conditions for 18 h the coupled product was obtained in 63% yield. Thus, it is clear that the use of sound wave activation is not just helpful but essential for performing this coupling reaction. Additionally, it is also worth noting that the reaction presented good utility and even tolerated ester groups, which are sensitive to basic conditions. Later, the same research group has used this protocol with some modifications for the synthesis of 1,3-dienes (Tetrahedron Lett. 2006, 47, 5075. DOI: 10.1016/j.tetlet.2006.05.088) 1,3-enynes (Synlett 2008, 1889. DOI: 10.1055/s-2008-1078507) (Z)-(2-chlorovinyl)alkenes (Tetrahedron Lett. 2008, 49, 4713. DOI: 10.1016/j.tetlet.2008.05.129) and symmetrical biaryls (Synlett 2008 2321. DOI: 10.1055/s-0028-1087244)

The Sonogashira reaction catalyzed by Copper- and Ligand-free Pd(0) Nanoparticles under Ultrasound Irradiation

Indian researchers disclosed in 2005 the first ultrasound-mediated Pd(0) nanoparticle-catalyzed cross-coupling reaction between aryl iodides or bromides and terminal acetylenes (Sonogashira reaction) (J. Org. Chem. 2005, 70, 4869. DOI: 10.1021/jo0503815). It was found that this reaction worked well with a large number of substrates in the absence of any further phosphine ligand or copper co-catalyst. The reaction was examined in acetone as well as in IL [bbim]BF4 under basic conditions. It was found that use of the molecular solvent furnished the desired coupled products in a substantially shorter time than when using IL, but in slight lower yields. Although, the use of IL requires more time for complete reaction, it allowed the recycling and reuse of the catalyst with little loss of activity after five runs. In order to learn the importance of ultrasound irradiation on the reaction, it was repeated under silent conditions (without ultrasound) and in this case no change took place even after several hours of stirring. Besides the improvement in terms of reaction time and yields, it is important to mention that no homocoupling between terminal alkynes (Glaser coupling) was found in the reactions employing aryl iodides, while homocoupled products were present to the extent of just 6-7% for aryl bromides.

Synthesis of 1-ferrocenyl-2-arylacetylenes under ultrasound irradiation

Although most of ultrasound-mediated cross-coupling reactions are geared towards functionalizing organic compounds, they are also applicable to substrates containing an inorganic moiety. The group of Baohua Chen from Lanzhou University, China, reported the palladium-catalyzed coupling reaction of ethynylferrocene with aryl iodides (Sonogashira coupling) under ultrasound irradiation (Catal. Comm. 2008, 9, 976. DOI: 10.1016/j.catcom.2007.09.039). The protocol afforded the desired products in 0-95% yields in 25-35 min of reaction. Besides the good yields and shorter reaction times, the main advantage of this method is the use of small loadings of cheap, commercially available PdCl2 as catalyst. The scope of the reaction is quite broad, but electron-poor aryl iodides were generally superior to electron-rich ones

R. A. W. N. Filho, Org. Chem. Highlights 2009, June 25.