The sonogashira cross coupling reaction has been employed in a wide variety of areas, due. Onepot iridium catalyzed ch borylationsonogashira cross. Sonogashira coupling3 is versatile and has been applied to prepare several terminal and internal acetylenes. We employed three metalcoordination structures as templates to control the sonogashira cross coupling reactions on a au111 surface catalyzed by loaded pd. Supported palladium catalysts are widely used in the suzuki, heck, and sonogashira cross coupling reactions. The sonogashira crosscoupling reaction was complete in five hours, giving product b in good yield table 2, entry 1. The pdcl 2 pph 3 2catalyzed sonogashira coupling reaction, in good to high yields, was performed in an ionic liquid bmimpf 6 in the absence of a copper salt. Sonogashira coupling catalyzed by palladium on polymer. Microwave method the sonogashira coupling reaction is a source of interest and is widely used in both industry and in academia. 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. Recent advances in coppercatalyzed cs crosscoupling. The structure of target products 3a3u was confirmed and characterized by 1h nmr, c nmr, and hrms.
The sonogashira reaction 12 scheme 1 is a robust and broadly applicable pdcatalysed bondforming process that, alongside the suzukimiyaura reaction, has steadily become an indispensible tool for cc bond formation in the pharmaceutical industry. Palladiumcatalyzed phosphine, copperfree and aerobic. Carboncarbon coupling reactions via transitionmetalcatalyzed processes have been intensively developed for their important synthetic applications. The catalytically active moiety is formed in situ, in a straightforward and user. Optimization of an efficient and sustainable sonogashira crosscoupling portocol philipp emanuel walter cross coupling reactions are a wellestablished tool in modern organic synthesis and play a crucial role in the synthesis of a high number of organic compounds. Rapid catalyst evaluation for sonogashira coupling in. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. A copperfree sonogashira coupling reaction in ionic. In addition to the suzuki coupling of aryl chlorides and. Classification and properties of palladium catalysts. In order to simplify the sonogashira reaction protocol, several important aspects have to be improved.
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. Stille, suzuki, and sonogashira couplings crosscoupling. We herein present a new catalytic system for the palladium. 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. Using spartan molecular modeling kit an explanation for the failure to employ analogues method in the synthesis of mtep was sought. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. Sonogashira reaction of aryl and heteroaryl halides with terminal.
Pharmaceuticals free fulltext improved syntheses of. The sonogashira crosscoupling, a key step in the syntheses of the mglu5 antagonists mmpep and mtep, provided an improved threestep method for the preparation of mmpep in 62% overall yield. We applied a continuous flow device for rapid catalyst screening of 4 heterogeneous catalysts over 6 sonogashira coupling reactions together with longevity estimation. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds. Palladiumcatalyzed sonogashira coupling reactions in. As early as 1975, heck 10, cassar 11 and sonogashira 12 independently discovered this reaction. Palladiumcatalyzed the sonogashira coupling reaction of 3halogen2aminopyridines 1 with terminal alkynes 2 afforded the corresponding 21 target products 3a3u in the presence of palladium catalyst. Ligand, copper, and aminefree sonogashira reaction of aryl. Available 2, 2dipyridylamine was used as a supporting ligand in the palladiumcatalyzed sonogashira crosscoupling reaction. This method represents a facile approach to synthetically useful. This reaction is an extension to cassar and dieck and heck reactions, that carries coupling with the use of palladium catalyst.
Both of these reactions make use of a palladium catalyst to carry out. Templatecontrolled sonogashira crosscoupling reactions. Synthesis and properties of arylnaphthylalkynes felix lederle, frederick meyer, christian kaldun, jan c. The sonogashira reaction also called the sonogashirahagihara reaction is the cross coupling of aryl or vinyl halides with terminal alkynes to. A new catalyst that derives from commercially available precursors for copperfree, pdcatalyzed sonogashira reactions at the sustainable ppm level of precious metal palladium under mild aqueous micellar conditions has been developed. Large gold particles are much more selective than small ones, consistent with this view. Sonogashira reaction is the spsp2 carbon crosscoupling reaction of terminal alkynes with aryl halides or alkenyl halide. The sonogashira crosscoupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Metal catalyzed sonogashira coupling reaction is a. Cuoxygen complexes liebeskind and coworkers reported a mild synthesis of thioethers via cui catalyzed coupling of boronic acids with nthioimides in good yields scheme 10. Sep 08, 2016 while the sonogashira reaction can be effectively carried out in a variety of media 12, in the general sense this process clearly relies upon the use of dipolar aprotic solvents, in particular dmf. We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for a. However, tolerance of aryl bromides to chb made possible a subsequent sonogashira crosscoupling to access the desired. The reaction has become an essential tool in the synthesis of these compounds, which.
However, due to both economical and environmental concern, development of novel. Kanuru 1, minthco tikhov, simon humphrey, john kyffyn, anthoula papageorgiou1,marc armbruster 1,david jefferson1, jonathan burton2 and richard lambert1 1department of chemistry, university of cambridge, cambridge,uk. C bonds in academic as well as industrial communities. Sonogashira reaction is the spsp2 carbon cross coupling reaction of terminal alkynes with aryl halides or alkenyl halide. A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. The reaction of aryl halides or vinyl halides with terminal alkynes catalyzed by a pdiicui system is known as the sonogashira coupling, and. Mechanistic insights and implications of dearomative rearrangement in copperfree sonogashira cross coupling catalyzed by pdcyphine adrian m.
What is the best procedure for sonogashira coupling. This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copperi cocatalyst, and an amine base. The sonogashira cross coupling reaction has become one of the most important methods in the formation of carboncarbon bonds over the past three decades, which plays an important role in the synthesis of pharmaceuticals, agrochemicals and functional materials. We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for an efficient template.
It is loosely based on the original publication of sonogashira in 1975 and the previous. Sonogashira coupling countable and uncountable, plural sonogashira couplings organic chemistry a crosscoupling reaction used in organic synthesis to form carbon carbon bonds. In organic chemistry portal it is written that hiyama coulping requires an activating agent such as fluoride ion or a base because crucial for the success of the hiyama coupling is the polarization of the sic bond. This graphic shows the mechanism of the sonogashira coupling. The sonogashira crosscoupling reaction has been employed in a wide variety of areas. Sonogashira coupling pdf uses of the sonogashira coupling. As expected, the reaction of terminal alcohol 7 with 2iodothioanisole 9 proceeded slowly, and was accompanied by significant polymerization. People have used the glaser reaction to do this, they basically used a bis with dialkyne linkages. 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. Desulfitative sonogashira type cross coupling the desulfitative sonogashira type.
Heck and sonogashira couplings in aqueous media application. The sonogashira coupling is one of the straightforward and powerful methods for formation of csp 2csp bonds and has been used in numerous synthetic ventures. This video looks at the proposed mechanism for the sonogashira coupling reaction. Pdf efficient sonogashira and a3 coupling reactions. Palladiumcatalyzed sonogashira and hiyama reactions using. Sonogashira coupling this coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copperi cocatalyst, and an amine base. This pdcatalyzed crosscoupling reaction presents a facile access to alkynyl cglycosides. The influences of different kinds of catalyst loading, bases, substrates and temperature were. The entire aqueous reaction medium can be easily recycled using an inflask extraction. Modern fields use it such as with the construction of nanostructures chinchilla, 2007.
Sonogashira coupling catalyzed by gold nanoparticles. The sonogashira cross coupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Asymmetric synthesis of oxindoles containing trifluoromethylated quaternary stereogenic centers dr. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have. Supporting information sonogashira reaction using arylsulfonium salts as cross coupling partners zeyu tian, shimeng wang, sujiao jia, haixia song, chengpan zhang school of chemistry, chemical engineering and life science, wuhan university of technology, 205 luoshi road, wuhan, 430070, china. While the sonogashira reaction can be effectively carried out in a variety of media, in the general sense this process clearly relies upon the use of dipolar aprotic solvents, in particular dmf. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important. While the sonogashira reaction can be effectively carried out in a variety of media 12, in the general sense this. A variety of measurements indicate that aunanoparticle catalyzed sonogashira coupling of iodobenzene and phenylacetylene is predominantly a heterogeneous process. S1 mechanistic insights and implications of dearomative rearrangement in copperfree sonogashira crosscoupling catalyzed by pdcyphine adrian m.
The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form. Palladiumcatalyzed phosphine, copperfree and aerobic sonogashira coupling in aqueous media chun liu, fanying bao, and qijian ni state key lab of fine chemicals, dalian university of technology, dalian 116024, p r china. Palladiumcatalyzed cross coupling reactions are among the most employed organic transformations for the generation of c. Highly regioselective c5 alkynylation of imidazoles by. Optimization of an efficient and sustainable sonogashira cross coupling portocol philipp emanuel walter cross coupling reactions are a wellestablished tool in modern organic synthesis and play a crucial role in the synthesis of a high number of organic compounds. There remained, however, a need to develop reaction conditions for. Templatecontrolled sonogashira crosscoupling reactions on a. Scope and limitations of a dmf bioalternative within. Sonogashirahagihara reactions of halogenated glycals.
Ligand, copper, and aminefree sonogashira reaction of. Activation of the silane with base or fluoride ions tasf, tbaf leading to a pentavalent silicon compound is a first necessary step. Optimization of an efficient and sustainable sonogashira. But the reaction is fraught with a limitation, in that it often results in considerable yields of hay coupling product homocoupling of terminal acet. There are letters in the background so its easier to refer to the single steps in the text. Sonogashira cross coupling reaction is going to be used in a practical application. 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. Aug 10, 2016 this video gives a broad overview of the sonogashira coupling reaction and how you would go about predicting product for it. Xingfeng bai department of chemistry, national university of singapore, 3 science drive 3, 117543 singapore, singapore. 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. Borylated aryl alkynes have been synthesized via onepot iridium catalyzed ch borylation chbsonogashira crosscoupling of aryl bromides. 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. The application of the above reaction in a microflow system in conjunction with an imm micromixer was also successful. Therefore, this reaction is generally known as the sonogashira coupling.
The dft calculations indicated that meaningful isolated yields were. Exp 35 sonogashira coupling formal lab report chem 369. Alternatively, you can download the file locally and open with any standalone pdf reader. Substantial leaching of au into the solution phase occurred during reaction, but the resulting supernatant liquid exhibited immeasurably low. Cc coupling, heck reaction, metal nanoparticles, polymer, sonogashira reaction, suzuki reaction. General procedure for sonogashira coupling reactions in a 4 ml screwcap vial, 0. Palladiumcoppercatalyzed sonogashira crosscoupling reaction of aryl halides with a variety of terminal alkynes under aminefree conditions in dimethylformamide dmf at 80 c gave internal arylated alkynes using pdcl2mecn2 with phosphinefree hydrazone 2a as a ligand and cui as the cocatalyst in good yields. This reaction is one of the most effective methods to form new carboncarbon bonds 1 9. Sonogashira crosscoupling an overview sciencedirect topics. Its ability to form carboncarbon bonds makes it particularly useful in syntheses of specific molecules and has thus been employed in the production of various drugs.
The reaction conditions are mild, and many reactions can be performed at room temperature. Sonogashira coupling reaction with diminished homocoupling. You can look at example, conditions and references for sonogashira coupling in my recent book organic syntheses based on name reactions. Pdf on jan 1, 2017, qing zhu and others published palladiumcatalyzed sonogashira coupling reaction of 2amino3bromopyridines with. The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. Pdf the coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium and other transition metals, commonly termed as sonogashira. Simple, efficient copperfree sonogashira coupling of. Sonogashira coupling of 5 and 7bromoquinolines with alkynes in the presence of palladium0 and copperi iodide gives alkynylsubstituted quinolines in good yield.
Reactions were conducted in a mixture of ch 3 cnh 2 o various proportion as solvent using a selfmade watersoluble pd0 complex 10 to 20 mol%. 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. This file is licensed under the creative commons attributionshare alike 3. Aug 10, 2016 this video looks at the proposed mechanism for the sonogashira coupling reaction. Metal catalyzed sonogashira coupling reaction is a heterogeneous process. Maka, yee hwee limb, howard jongb, yong yangb, charles w. Alkynylsubstituted azoles represent important structural cores of several biologically active molecules 1 and organic functional materials. Supporting information sonogashira reaction using arylsulfonium salts as crosscoupling partners zeyu tian, shimeng wang, sujiao jia, haixia song, chengpan zhang school of chemistry, chemical engineering and life science, wuhan university of technology, 205 luoshi road, wuhan, 430070, china. Palladiumcatalyzed sonogashira coupling reaction of 2amino. Catalyzed enantioselective sequential heck sonogashira coupling. Pdf recent advances in sonogashira reactions researchgate.
Palladiumcatalyzed sonogashira coupling reaction of 2. The alkynylation reaction of aryl halides using aromatic acetylenes was reported in 1975 in. Nanoparticles derived from fecl3 containing the ligand xphos and only 500 ppm pd effect sonogashira couplings in water between rt and 45 c. Mechanistic insights and implications of dearomative. Herein, we report on our findings of the sonogashirahagihara reaction with 1iodinated and 2brominated glycals using several aromatic and aliphatic alkynes. Sonogashira crosscoupling reaction is going to be used in a practical application. 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 sp 2 sp carbon carbon bond formation reactions in organic synthesis, frequently employed in the synthesis of natural products, biologically active molecules, heterocycles. Selection of the most appropriate catalyst for pdcatalyzed sonogashira coupling often requires time and resources.
Pdf recent advances in sonogashira reactions rafael. Sonogashira couplings catalyzed by fe nanoparticles. Indeed, some 41% of all sonogashira reactions reported using aryl iodides can be linked to the use of dmf as a solvent. The sonogashira crosscoupling reaction has been employed in a wide variety of areas, due. Both the palladium precatalyst and ligand are commercially available, ben 2019 chemical science hot article collection 2019 chemsci pick of the week collection. Pdf palladiumcatalyzed sonogashira coupling reaction of 2. Supported palladium catalysts are widely used in the suzuki, heck, and sonogashira crosscoupling reactions. You may do so in any reasonable manner, but not in. The use of an ionic liquid allows for the facile separation and recycling of the catalyst.
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