The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon – carbon bonds.

The Sonogashira cross-coupling reaction has been employed in a wide variety of areas, due to its usefulness in the formation of carbon – carbon bonds.

The reaction can be carried out under mild conditions, such as at room temperature, in aqueous media, and with a mild base, which has allowed for the use of the Sonogashira cross-coupling reaction in the synthesis of complex molecules.

This results in the increased reactivity of the reagents and the ability of the reaction to be carried out at room temperature, making the Sonogashira cross-coupling reaction a highly useful reaction, particularly in the alkynylation of aryl and alkenyl halides.

The synthesis of these natural products involved the use of Sonogashira cross-coupling to build the carbon backbone of each molecule.

Natural products (+)-( S )- laudanosine and (–)-( S )- xylopinine synthesized using the Sonogashira cross-coupling reaction.

Vinyl iodides are the most reactive vinyl halides to Pd < sup > 0 </ sup > oxidative addition, and their use is therefore most frequent for Sonogashira cross-coupling reactions due to the usually milder conditions employed.

Use of the Sonogashira cross-coupling reaction in the synthesis of SIB-1508Y.

It has become so well known that often, all reactions that use a palladium ( 0 ) catalyst to couple a sp < sup > 2 </ sup > and even sp < sup > 3 </ sup > halide or triflate with a terminal alkyne, regardless of whether or not a copper co-catalyst is used, are termed " Sonogashira reactions ," despite the fact that these reactions are not carried out under true Sonogashira reaction conditions.

: Catalytic cycle for the Sonogashira reaction

The Sonogashira reaction is typically run under mild conditions.

As a result, when running a Sonogashira reaction with a copper co-catalyst, it is necessary to run the reaction in an inert atmosphere to avoid the unwanted dimerization.

Copper-free variations to the Sonogashira reaction have been developed to avoid the formation of the homocoupling products.

Arenediazonium salts have been reported as an alternative to aryl halides for the Sonogashira coupling reaction.

Some recent examples can be found about the use of dendritic palladium complex catalysts for the copper-free Sonogashira reaction.

The recyclable polymeric phosphane ligand shown below is obtained from ring-opening metathesis polymerization of a norbornene derivative, and has been used in the copper cocatalyzed Sonogashira reaction of methyl piodobenzoate and phenylacetylene using Pd ( dba )< sub > 2 </ sub >• CHCl < sub > 3 </ sub > as a palladium source.

in the copper-free Sonogashira coupling reaction of aryl

The coupling of a terminal alkyne and an aromatic ring is the pivotal reaction when talking about applications of the copper-promoted or copper-free Sonogashira reaction.

The list of cases where the typical Sonogashira reaction using aryl halides has been employed is large, and choosing illustrative examples is difficult.

Many metabolites found in nature contain alkyne or enyne moieties, and therefore, the Sonogashira reaction has found frequent utility in their syntheses.

The first reaction is a Barbier reaction with propargylic bromide in water ( green chemistry ) and the second reaction is a Sonogashira coupling.

Sonogashira coupling, where anilines are transformed into diazonium salt and furtherly converted into alkyne by coupling with phenylacetylene.

It is derived from vinylic systems and terminal acetylenes by using a configuration-retention stereospecific procedure such as the Sonogashira reaction.

Synthesis of an alk-2-ynylbuta-1, 3 ,- diene accomplished by Sonogashira coupling.

In one study oxazoles were prepared via a one-pot synthesis consisting of the condensation of propargyl amine and benzoyl chloride to the amide, followed by a Sonogashira coupling of the terminal alkyne end with another equivalent of benzoylchloride, and concluding with p-toluenesulfonic acid catalyzed cycloisomerization:

In organic synthesis this reaction is often replaced by palladium coupling reactions such as the Heck reaction, the Hiyama coupling and the Sonogashira coupling.

Sonogashira couplings are employed in a wide array of synthetic reactions, primarily due to their success in facilitating the following challenging transformations:

Terminal alkynes can also be coupled to aryl or vinyl halides as in the Sonogashira coupling.

Both of these reactions make use of a palladium catalyst to carry out the coupling, while Sonogashira uses both palladium and copper cataylysts simultaneously.

A search for the term " Sonogashira " in Scifinder provides over 1500 references for journal publications between 2007 and 2010.

In addition, deaerated conditions are formally needed for Sonogashira coupling reactions because the palladium ( 0 ) complexes are unstable in the air, and oxygen promotes the formation of homocoupled acetylenes.

The Sonogashira coupling is applied in the synthesis of cross-conjugated oligo ( phenylene enynylene ) s and phenanthroline derivatives.

In an inverse Sonogashira coupling the reactants are an aryl or vinyl compound and an alkynyl halide.

Proposed copper-free mechanism for Sonogashira Reaction.

Recently, a nickel-catalyzed Sonogashira coupling has been developed which allows for the coupling of non-activated alkyl halides to acetylene without the use of palladium, although a copper co-catalyst is still needed.

Additionally, iron-catalyzed Sonogashira couplings have been investigated as relatively cheap and non-toxic alternatives to palladium.

formation of catalysts suitable for Sonogashira couplings.

The Suzuki Reaction, an extremely popular cross-coupling chemical reaction ( shared winner of the 2010 Nobel Prize for chemistry ).

Together with the other palladium-catalyzed cross-coupling reactions, this reaction is of great importance, as it allows one to do substitution reactions on planar centers.

The reaction is usually performed under inert atmosphere using dehydrated and degassed solvent, as oxygen causes the oxidation of the palladium catalyst and promotes homo-coupling of organic stannyl compounds, and these side reactions lead to a decrease in the yield of the desired cross-coupling reaction.

The cross-coupling reaction can be inhibited by ligands of a high donor number.

Recent applications of the Suzuki – Miyaura cross-coupling reaction in organic synthesis

The Hiyama-coupling is a palladium-catalyzed cross-coupling reaction of organosilanes with organic halides used in organic chemistry to form carbon-carbon bonds ( C-C bonds ).

Several syntheses of substituted dendralenes have been reported, one via an allene, one via a Horner – Wadsworth – Emmons reaction, one via a cross-coupling reaction and one from an allylic carbonate.