The characteristic feature of this reaction is that the two. Ligand, copper, and aminefree sonogashira reaction of aryl. The sonogashira cross coupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Sonogashira reactions of unactivated alkyl bromides and iodides m. Scheme 6 formation of methyl 2phenylacrylate by heck coupling. But it is a very ecconomical alternative due to low costs associated with grignard reagents.
This reaction is an extension to cassar and dieck and heck reactions, that carries coupling with the use of palladium catalyst. Pdf recent advances in sonogashira reactions researchgate. As a synthetic organic chemist you will have built many carboncarbon bonds and most probably in some occasions this will have been between sp2 and sp carbons. Sonogashira coupling followed by the transannular dielsalder reaction to construct the core skeleton of dynemicin a. When copper catalystfree reaction was carried out with copper milling balls as a source of. Sonogashira crosscoupling an overview sciencedirect topics. The reactions conditions, mechanistic features and weaknesses of the sonogashira coupling have been discussed. This video looks at the proposed mechanism for the sonogashira coupling reaction. Guidelines for sonogashira crosscoupling reactions. Cc bond formation using transition metal catalyzed sonogashira coupling reaction is an indispensable tool in synthetic organic chemistry. Hydrazonepromoted sonogashira coupling reaction with aryl bromides at low palladium loadings. Mar 09, 2016 a cuicatalysed sonogashira type cross coupling reaction with aliphatic or aromatic bromoisoxazolines or nalkoxyimidoyl bromides and alkynes is reported. The sonogashira coupling reaction is one of the most widely used methods for the coupling of vinyl or aryl halides with terminal alkynes to form conjugated enynes or aryl.
The so called sonogashira crosscoupling reaction scheme 1, the most important of the latter carboncarbon bond formations, is the reaction between an aryl or vinyl halides with a. The most important improvement for the sonogashira coupling is probably to perform this reaction under copper. Copperfree sonogashira coupling reaction with pdcl2 in water. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. The sonogashira coupling was proposed in the year 1975 by nobue hagihara, yasuo tohda and kenkichi sonogashira in their publication.
Scope and mechanistic limitations of a sonogashira. The use of 1 mol % pdcl2 in the presence of pyrrolidine allows the coupling reaction to proceed at room temperature or 50 c with good to excellent yields. Here we describe examples where the sonogashira reaction serves as a key coupling step in the convergent synthesis of natural products. Synthetic procedures and spectral data for compounds 2. Recent advances in sonogashira reactions chemical society. It is an extension to the cassar and dieck and heck reactions, which afford the same reaction products, but use harsh reaction conditions, such as high temperature, to do so.
The method exhibits good functional group tolerance and provides target 4. Pdcatalyzed sonogashira coupling is currently the most practical method for synthesizing arylvinyl acetylenes from the corresponding terminal alkynes and aryl halides. Desulfitative sonogashira type cross coupling the desulfitative sonogashira type. A cuicatalysed sonogashiratype cross coupling reaction with aliphatic or aromatic bromoisoxazolines or nalkoxyimidoyl bromides and alkynes is reported. This video gives a broad overview of the sonogashira coupling reaction and how you would go about predicting product for it. So, i hope you are enjoying the carbon carbon bond formation reactions.
This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copperi cocatalyst, and an amine base. For cc coupling i used 10 mol % pdcl2 pph32 in combination with cui and tea, reaction proced nicely in nmp, a similar cc coupling reaction was sluggish under this condtion so i prefered. The organic layer was washed with brine, dried over na2so4, decanted and concentrated under reduced pressure. Introduction sonogashira reaction is the spsp2 carbon cross coupling reaction of terminal alkynes with aryl halides or alkenyl halide. The reaction mixture was poured into saturated aqueous nahco3 and extracted with etoac. This material is available free of charge via the internet at pdf. This graphic shows the mechanism of the sonogashira coupling. This reaction is one of the most effective methods to form new carboncarbon bonds 1 9. A sonogashira coupling reaction method to join terminal alkynes to the imidazole backbone was developed and investigated. Sonogashira crosscoupling reaction is going to be used in a practical application. Oxoiminatophosphane complexes under mild conditions. Pdf the coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium and other transition metals, commonly termed as sonogashira. The alkyne moiety is usually introduced via its copper salt. Introduction the sonogashira reaction 1,2 scheme1 is a robust and broadly applicable pdcatalysed bondforming process that, alongside the suzukimiyaura reaction 3, has steadily become.
A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds. Copperfree sonogashira coupling reaction with pdcl2 in. In organic chemistry, a sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. Occasionally, this reaction is also referred to as the sonogashirahagihara reaction. Although the sonogashira coupling of acetylenes and vinylaryl halides has been applied for. The reaction typically proceeds in the presence of a palladium0 catalyst, a copperi cocatalyst, and an imine base.
Rapid catalyst evaluation for sonogashira coupling in. There are letters in the background so its easier to refer to the single steps in the text. The results of these crosscoupling reactions are summarized in tables 1 and 2. Suzuki coupling suzuki coupling is the reaction of vinyl or aryl boronic acids with aryl and vinyl halides or triflates using a palladium catalyst. The sonogashira reaction is today the most versatile and powerful way to generate aryl alkynes, a moiety recurring in many pharmaceutical and natural products. Sonogashira coupling is the coupling of terminal alkynes with aryl and vinyl halides in the presence of a palladium 0 catalyst, a cui cocatalyst, and an. Stille, suzuki, and sonogashira couplings crosscoupling. Interesting is the development of concept of copperfree sonogashira reaction in which cui catalyst was not used scheme 2. The sonogashira cross coupling reaction is the organic reaction of an organohalide with a terminal alkyne to give the coupled product using a palladium catalyst, a copper catalyst, and base. The side product from homocoupling reaction of two terminal acetylenes in the sonogashira reaction can be reduced to about 2% using an atmosphere of. Over recent decades, palladiumcatalysed crosscoupling reactions have gained an enormous. Onepot iridium catalyzed ch borylation sonogashira. Nov 24, 2004 a mild protocol for the copperfree sonogashira coupling of aryl iodides with terminal acetylenes in water under aerobic conditions has been developed.
Desulfitative sonogashiratype crosscoupling the desulfitative sonogashiratype. Stille cross coupling reaction palladium catalyst with organotin useful to construct new carboncarbon bonds sonogashira cross coupling reaction palladium catalyzed copper i cocatalyst amine base coupling of terminal alkynes with aryl or vinyl halides. Mechanism of copperfree sonogashira reaction operates through. Mar 06, 2012 the utility of sonogashira coupling reaction for the derivatization of aryl halides with fluorescent alkyne.
Palladiumcatalyzed sonogashira coupling reaction of 2. But the sonogashira reaction uses copper and palladium catalysts continuously. Sonogashira coupling reaction with diminished homocoupling. Sonogashira crosscoupling an overview sciencedirect. Pdf recent advances and perspectives in coppercatalyzed. The sonogashira coupling the sonogashira reaction offers an extremely useful route into aryl and alkenylalkynes. Sonogashira cross coupling chemistry bibliographies. Oxoiminatophosphane complexes under mild conditions d.
Mechanism of copperfree sonogashira reaction operates. Ligand, copper, and aminefree sonogashira reaction of. In addition to the suzuki coupling of aryl chlorides and. A few articles report the sonogashira coupling reaction using. The stille crosscoupling reaction is the organic reaction of an organohalide with an organostannane compound to give the coupled product using a palladium catalyst. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form.
Preceding the sonogashira reaction, heck and diek and cassar reactions reported the arylation or alkenylation of alkenes via phosphanepalladium complexes. Efficient sonogashira coupling reaction catalyzed by palladiumii. The first applications of carbene ligands in cross couplings of alkyl electrophiles. Pdf on jan 1, 2017, qing zhu and others published palladiumcatalyzed sonogashira coupling reaction of 2amino3bromopyridines with.
The reaction has become an essential tool in the synthesis of these compounds, which. The reaction was first reported by kenkichi sonogashira and nobue hagihara in 1975. The coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium and other transition metals, commonly termed as sonogashira cross coupling reaction, is one of the most important and widely used sp2sp carboncarbon bond formation reactions in organic synthesis, frequently employed in th cross coupling reactions in organic synthesis. A mild protocol for the copperfree sonogashira coupling of aryl iodides with terminal acetylenes in water under aerobic conditions has been developed. Coupling reactions coupling reactions occur between organometallic with organic halide with the aid of a metal containing catalyst. Ebook or pdf edited book email encyclopedia article govt. Sonogashira or sonogashirahagihara coupling is a reaction that includes palladiumcopper catalysts and terminal alkynes and organic halides as the partners. If such a sequence could also be accomplished in a onepot fashion, it would streamline the synthesis of borylated aromatic alkynes while allowing access to target molecules bearing the contraelectronic substitution patterns often associated with chb reactions. It is loosely based on the original publication of sonogashira in 1975 and the previous. The sonogashira crosscoupling reaction is the organic reaction of an organohalide with a terminal alkyne to give the coupled product using a palladium catalyst, a copper catalyst, and base. The utility of sonogashira coupling reaction for the derivatization of aryl halides with fluorescent alkyne. Optimization of an efficient and sustainable sonogashira.
The intermediate monohalide monostannane cyclises under the reaction conditions to yield the desired product. Scope and mechanistic limitations of a sonogashira coupling. In these reactions, coupling products 47 in various yields were still obtained table 2. This pdcatalyzed crosscoupling reaction presents a facile access to alkynyl cglycosides. Aug 10, 2016 this video gives a broad overview of the sonogashira coupling reaction and how you would go about predicting product for it. A booming methodology in synthetic organic chemistry. The stillekelly coupling is a palladium catalysed intramolecular cross coupling using distannanes such as hexabutyldistannane or hexamethyldistannane. Herein, we report on our findings of the sonogashirahagihara reaction with 1iodinated and 2brominated glycals using several aromatic and aliphatic alkynes. Guidelines for sonogashira crosscoupling reactions sussex. Aug 10, 2016 this video looks at the proposed mechanism for the sonogashira coupling reaction. People have used the glaser reaction to do this, they basically used a bis with dialkyne linkages. It employs a palladium catalyst as well as copper cocatalyst to form a carboncarbon bond between a terminal alkyne and an aryl or vinyl halide. Sonogashira cross coupling reaction is going to be used in a practical application.
Heterogeneous stille and sonogashira crosscoupling. Palladiumcatalysed coupling chemistry acros organics. The protocol we developed employs catalytic amount of copperi, nontoxic ligand bathophenanthroline and is tolerant to a wide range of functional groups and is therefore particulary adapted in the context of drug discovery. Mechanism, references and reaction samples of the sonogashira coupling. Palladiumcatalyzed sonogashira coupling reaction of 2amino. Metal catalyzed sonogashira coupling reaction is a heterogeneous process. Sonogashirahagihara reactions of halogenated glycals.
Sonogashira coupling major reference works wiley online. The sonogashira coupling reaction is one of the most widely used methods for the coupling of vinyl or aryl halides with terminal alkynes to form conjugated enynes or aryl alkynes. The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. Turn on the stirrer and stir the resulting mixture vigorously at room temperature until the reaction is complete monitored by tlc, gc, lc, etc. Scope and limitations of a dmf bioalternative within. The reaction of aryl halides or vinyl halides with terminal alkynes catalyzed by a pdiicui system is known as the sonogashira coupling, and. The coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium and other transition metals, commonly termed as sonogashira crosscoupling reaction, is one of the most important and widely used sp2sp carboncarbon bond formation reactions in organic synthesis, frequently employed in th cross coupling reactions in organic synthesis. The other type of coupling is homocoupling, in this reaction two similar.
What is the best procedure for sonogashira coupling. Sonogashira couplings enable convergent synthesis strategies, which are of value due to their advantages in efficiency over more linear synthesis strategies. Jan 14, 20 the so called sonogashira cross coupling reaction scheme 1, the most important of the latter carboncarbon bond formations, is the reaction between an aryl or vinyl halides with a terminal acetylene catalysed generally by a palladium catalyst. Sonogashira reaction of aryl and heteroaryl halides with terminal. General characteristics the cross coupling reaction between an aryl or alkyl halide and a terminal alkyne catalyzed by the combination of pd0, copper iodide, and an amine is called the sonogashirahagiwara reaction. Introduction sonogashira reaction is the spsp2 carbon crosscoupling reaction of terminal alkynes with aryl halides or alkenyl halide.
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