The first heck crosscoupling reaction starting from deprotected nucleoside was reported in 1998 by barbas et al. The stille reaction was the only reliable coupling method at 50g scale. We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for a. Since its discovery, sonogashira 10 coupling has been extensively studied in efforts to understand its mechanism as well. Modified palladiumcatalyzed sonogashira crosscoupling. Templatecontrolled sonogashira crosscoupling reactions on a. Pdf palladiumcatalyzed sonogashira coupling reaction of 2. It is possible that the sonogashira cross coupling of haloaryl carboxylic acids and unactivated aryl bromides with terminal alkynes will be achieved by the methodology above. Optimization of an efficient and sustainable sonogashira. Catalyzed enantioselective sequential hecksonogashira. Sonogashira reaction transitionmetalcatalyzed crosscoupling reaction in water at room temperature using tpgs750m. A fast sonogashira reaction of various aryl halides xi, br, cl with alkynes in the presence of 3 mol% of pdcl 2 pph 3 2 and 3 eq. Scope and mechanistic limitations of a sonogashira. Auxiliary groups favorably influenced meps and enabled coupling, which.
People have used the glaser reaction to do this, they basically used a bis with dialkyne linkages. Sonogashira reaction using arylsulfonium salts as cross. This reaction is an extension to cassar and dieck and heck reactions, that carries coupling with the use of palladium catalyst. The alkyne moiety is usually introduced via its copper salt. 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. Desulfitative sonogashira type cross coupling the desulfitative sonogashira type. Aug 10, 2016 this video gives a broad overview of the sonogashira coupling reaction and how you would go about predicting product for it. Mechanism of copperfree sonogashira reaction operates. The results of these crosscoupling reactions are summarized in tables 1 and 2. The side product from homocoupling reaction of two terminal.
The reactions all start with the oxidative addition of the low valent metal into an organic electrophile e. The sonogashira coupling was proposed in the year 1975 by nobue hagihara, yasuo tohda and kenkichi sonogashira in their publication. This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copperi cocatalyst, and an amine base. Palladiumcatalyzed sonogashira coupling reaction of 2. Sonogashirahagihara reactions of halogenated glycals. Sonogashira coupling reaction with diminished homocoupling. A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. Sonogashira coupling reaction of iodobenzene 1a and phenylacetylene 2a in different ionic liquids. This reaction is one of the most effec tive methods to form new carboncarbon bonds 1 9. Although the sonogashira coupling of acetylenes and vinylaryl halides has.
We employed three metalcoordination structures as templates to control the sonogashira cross coupling reactions on a au111 surface catalyzed by loaded pd. As early as 1975, heck 10, cassar 11 and sonogashira 12 independently discovered this reaction. The copperfree sonogashira reaction has been explained. There are letters in the background so its easier to refer to the single steps in the text. Copperfree sonogashira coupling reaction with pdcl2 in water. Practical synthesis of aryl2methyl3butyn2ols from aryl. Pdf on jan 1, 2017, qing zhu and others published palladiumcatalyzed sonogashira coupling reaction of 2amino3bromopyridines with. But the reaction is fraught with a limitation, in that it often results in considerable yields of hay coupling product homocoupling of terminal acet. Pdf recent advances in sonogashira reactions researchgate. Heck crosscoupling reaction in aqueous solution was developed using only pdii as a precatalyst in water and in ch 3 cnh 2 o. 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 sonogashira reaction also called the sonogashirahagihara reaction is the cross coupling of aryl or vinyl halides with terminal alkynes to generate conjugated enynes and arylalkynes scheme 1.
The reaction conditions are mild, and many reactions can be performed at room temperature. This graphic shows the mechanism of the sonogashira coupling. Metal catalyzed sonogashira coupling reaction is a. A cuicatalysed sonogashiratype cross coupling reaction with aliphatic or aromatic bromoisoxazolines or nalkoxyimidoyl bromides and alkynes is reported. What is the best procedure for sonogashira coupling. Sonogashira coupling catalyzed by palladium on polymer.
Residual tin was minimized by slurring the coupling product in mtbe followed by recrystallization from ethyl acetate. Scope and mechanistic limitations of a sonogashira coupling. It is possible that the sonogashira crosscoupling of haloaryl carboxylic acids and unactivated aryl bromides with terminal alkynes will be achieved by the methodology above. Application of covalently anchored 2,4,6triallyloxy1,3,5triazine tat pdii complex over modified surface of sba15 to heck, suzuki, sonogashira and hiyama cross coupling reactions. Both of these reactions make use of a palladium catalyst to carry out. Supported palladium catalysts are widely used in the suzuki, heck, and sonogashira crosscoupling reactions. Recent advances in sonogashira reactions chemical society. Pdcatalyzed sonogashira coupling is currently the most practical method for synthesizing arylvinyl acetylenes from the corresponding terminal alkynes and aryl halides. Mechanism, references and reaction samples of the sonogashira coupling. It is loosely based on the original publication of sonogashira in 1975 and the previous. Sonogashira coupling reaction of iodobenzene 1a and. 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 stillekelly coupling is a palladium catalysed intramolecular cross coupling using distannanes such as hexabutyldistannane or hexamethyldistannane. The name of the reaction refers to the organometallic or nucleophilic partner. The sonogashira crosscoupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form. Rapid catalyst evaluation for sonogashira coupling in. The utility of sonogashira coupling reaction for the derivatization of aryl halides with fluorescent alkyne. 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 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 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. Microsoft word summer 20 omet practice problem set. Mechanism of copperfree sonogashira reaction operates through. A mild protocol for the copperfree sonogashira coupling of aryl iodides with terminal. Ligand, copper, and aminefree sonogashira reaction of aryl. Arylmagnesium bromides with 4methoxy, 4dimethylamino, 4fluoro and 4chloro substituents give high yields in the crosscoupling while heterocyclic grignard reagents turned out to be poor substrates for the reaction. The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. Files available from the acs website may be downloaded for personal use only.
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. Sonogashira coupling, has become a generally accepted method. This reaction provides a new and practical approach for the synthesis of substituted alkynes see scheme. Continued development of the sonogashira coupling has made it a well established and versatile reaction for the straightforward formation of cc bonds, forging the. The sonogashira coupling reaction of aryl or alkenyl halides with terminal acetylenes is the most straightforward method for the preparation of substituted alkynes 16, which are extensively used as building blocks in a great number of applications including the synthesis of pharmaceuticals 79, natural products and organic functional materials 10. Sonogashira reaction in water at room temperature using. The mechanism of the copperfree sonogashira crosscoupling was investigated using a model reaction with differently parasubstituted phenylacetylenes and 4iodobenzotrifluoride as coupling partners and a pd2dba3chcl3. 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. This reaction was first reported by kenkichi sonogashira and nobue hagihara in 1975. The advantages to using supported catalysts in organic synthesis include reagent stability, suitability for automation, ease of workup, recyclability, and lower pd contamination in the final product. Aug 10, 2016 this video looks at the proposed mechanism for the sonogashira coupling reaction. In stille coupling reaction, both substituted and nonsubstituted aryl halides are coupled with organotin compound in dmf at 90 c in the presence of licl. Efficient sonogashira coupling reaction catalyzed by palladiumii. The sonogashira coupling the sonogashira reaction offers an extremely useful route into aryl and alkenylalkynes.
Myers the stille reaction chem 115 harvard university. A carbopalladation mechanism was ruled out through a series of experiments in which the equivalent of a carbopalladation reaction. Two competing mechanisms for the copperfree sonogashira. A general asymmetric coppercatalysed sonogashira c sp 3. The sonogashira reaction is today the most versatile and powerful way to generate aryl alkynes, a moiety recurring in many pharmaceutical and natural products. A facile synthesis of functionalized bisarylethynyl benzene derivatives via silasonogashira reaction zhanglin zhou, lihua zhao, sean zhang, kent vincent, sity lam, dick henze hp laboratories hpl2010185 bisarylethynylbenzene derivatives, crosscoupling reaction, silasonogashira reaction. Palladiumcatalyzed sonogashira coupling reactions in. Sonogashira coupling3 is versatile and has been applied to prepare several terminal and internal acetylenes.
Coupling success was predicted by molecular electrostatic potential surfaces meps for the reagents there were within a narrow range 94 to 105 kj mol 1. Sonogashira reaction in water at room temperature using tpgs. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. The method exhibits good functional group tolerance and provides target 4. The intermediate monohalide monostannane cyclises under the reaction conditions to yield the desired product. Palladiumfree sonogashiratype crosscoupling reaction of. Postsynthetic modified mof for sonogashira crosscoupling. This video looks at the proposed mechanism for the sonogashira coupling reaction. In addition to the suzuki coupling of aryl chlorides and. Stille, suzuki, and sonogashira couplings crosscoupling. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds. Jun 15, 2015 a sonogashira coupling reaction method to join terminal alkynes to the imidazole backbone was developed and investigated.
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. Files are available under licenses specified on their description page. Simple, efficient copperfree sonogashira coupling of. The sonogashira cross coupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. In organic chemistry, a sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. This video gives a broad overview of the sonogashira coupling reaction and how you would go about predicting product for it. Heterogeneous stille and sonogashira crosscoupling reactions. Ligand, copper, and aminefree sonogashira reaction of.
Pdf recent advances in sonogashira reactions rafael. But it is a very ecconomical alternative due to low costs associated with grignard reagents. Arylmagnesium bromides with 4methoxy, 4dimethylamino, 4fluoro and 4chloro substituents give high yields in the cross coupling while heterocyclic grignard reagents turned out to be poor substrates for the reaction. The reaction typically proceeds in the presence of a palladium0 catalyst, a copperi cocatalyst, and an imine base. 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. Myers the heck reaction chem 115 harvard university. A sonogashira coupling reaction to functionalize an imidazole backbone was developed and investigated. The reaction has become an essential tool in the synthesis of these compounds, which. Mar 06, 2012 a guide to sonogashira crosscoupling reactions. This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copper i cocatalyst, and an amine base. Media in category sonogashira reactions the following 36 files are in this category, out of 36 total. Herein, we report on our findings of the sonogashirahagihara reaction with 1iodinated and 2brominated glycals using several aromatic and aliphatic alkynes.
Our initial study focused on the sonogashira crosscoupling between fluorescein iodide 1a and a homopropargylglycine hpgcontaining peptide 2a using a watersoluble 2amino4,6dihydroxypyrimidine adhp as the palladium ligand because adhp has been previously used successfully in the copperfree sonogashira reactions in organic solvents. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important. Now, an easy, quick and aerial copperfree methodology for the sonogashira reaction using readily available palladium complexes as catalyst has been reported. The reaction mechanism is not clearly understood, but the textbook mechanism revolves around a palladium cycle which is in agreement with the classical. This pdcatalyzed crosscoupling reaction presents a facile access to alkynyl cglycosides. 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. This catalyst exhibited an excellent activity for both sonogashira cross coupling and knoevenagel condensation reaction retaining its catalytic and uniform distribution of the active sites, palladium ii anchored on nheterocyclic carbene nhcpdii, for at least four cycles without losing its structural integrity. Sonogashira reaction is the spsp2 carbon crosscoupling reaction of terminal alkynes with aryl halides or alkenyl halide. The influence of substituents in aryl bromides, acetylenes, and phosphines.
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