The catalytically active moiety is formed in situ, in a straightforward and user. Microwave method the sonogashira coupling reaction is a source of interest and is widely used in both industry and in academia. Pdf efficient sonogashira and a3 coupling reactions. Asymmetric synthesis of oxindoles containing trifluoromethylated quaternary stereogenic centers dr. 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. This reaction is one of the most effective methods to form new carboncarbon bonds 1 9. Pdf recent advances in sonogashira reactions rafael. The sonogashira cross coupling reaction has been employed in a wide variety of areas, due. Sonogashira reaction of aryl and heteroaryl halides with terminal. S1 mechanistic insights and implications of dearomative rearrangement in copperfree sonogashira crosscoupling catalyzed by pdcyphine adrian m. Maka, yee hwee limb, howard jongb, yong yangb, charles w. Activation of the silane with base or fluoride ions tasf, tbaf leading to a pentavalent silicon compound is a first necessary step.
The sonogashira coupling was proposed in the year 1975 by nobue hagihara, yasuo tohda and kenkichi sonogashira in their publication. 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. Substantial leaching of au into the solution phase occurred during reaction, but the resulting supernatant liquid exhibited immeasurably low. We employed three metalcoordination structures as templates to control the sonogashira cross coupling reactions on a au111 surface catalyzed by loaded pd. Borylated aryl alkynes have been synthesized via onepot iridium catalyzed ch borylation chbsonogashira crosscoupling of aryl bromides. Palladiumcatalyzed sonogashira coupling reaction of 2amino. Palladiumcatalyzed sonogashira coupling reaction of 2.
The reaction has become an essential tool in the synthesis of these compounds, which. Sonogashira coupling catalyzed by palladium on polymer. Mechanistic insights and implications of dearomative. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds. Catalyzed enantioselective sequential heck sonogashira coupling. Aug 10, 2016 this video gives a broad overview of the sonogashira coupling reaction and how you would go about predicting product for it. 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%. 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. Ligand, copper, and aminefree sonogashira reaction of aryl. Desulfitative sonogashira type cross coupling the desulfitative sonogashira type. There remained, however, a need to develop reaction conditions for. Sonogashira coupling reaction with diminished homocoupling.
Mechanistic insights and implications of dearomative rearrangement in copperfree sonogashira cross coupling catalyzed by pdcyphine adrian m. Selection of the most appropriate catalyst for pdcatalyzed sonogashira coupling often requires time and resources. Therefore, this reaction is generally known as the sonogashira coupling. Sonogashira reaction is the spsp2 carbon crosscoupling reaction of terminal alkynes with aryl halides or alkenyl halide. Sonogashira coupling of 5 and 7bromoquinolines with alkynes in the presence of palladium0 and copperi iodide gives alkynylsubstituted quinolines in good yield. Scope and limitations of a dmf bioalternative within. The reaction conditions are mild, and many reactions can be performed at room temperature. Indeed, some 41% of all sonogashira reactions reported using aryl iodides can be linked to the use of dmf as a solvent. While the sonogashira reaction can be effectively carried out in a variety of media 12, in the general sense this. This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copperi cocatalyst, and an amine base. 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 couplings catalyzed by fe nanoparticles. Pdf palladiumcatalyzed sonogashira coupling reaction of 2.
The sonogashira reaction also called the sonogashirahagihara reaction is the cross coupling of aryl or vinyl halides with terminal alkynes to. However, due to both economical and environmental concern, development of novel. Metal catalyzed sonogashira coupling reaction is a heterogeneous process. 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. A copperfree sonogashira coupling reaction in ionic. Available 2, 2dipyridylamine was used as a supporting ligand in the palladiumcatalyzed sonogashira crosscoupling reaction. The dft calculations indicated that meaningful isolated yields were. This file is licensed under the creative commons attributionshare alike 3. The influences of different kinds of catalyst loading, bases, substrates and temperature were. 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.
Recent advances in coppercatalyzed cs crosscoupling. You may do so in any reasonable manner, but not in. The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. 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. In addition to the suzuki coupling of aryl chlorides and. 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 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. Direct borylation of aryl alkynes encountered problems related to the reactivity of the alkyne under chb conditions.
Palladiumcatalyzed cross coupling reactions are among the most employed organic transformations for the generation of c. Pdf recent advances in sonogashira reactions researchgate. Cc coupling, heck reaction, metal nanoparticles, polymer, sonogashira reaction, suzuki reaction. The sonogashira crosscoupling reaction was complete in five hours, giving product b in good yield table 2, entry 1. 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. Metal catalyzed sonogashira coupling reaction is a. The structure of target products 3a3u was confirmed and characterized by 1h nmr, c nmr, and hrms. We applied a continuous flow device for rapid catalyst screening of 4 heterogeneous catalysts over 6 sonogashira coupling reactions together with longevity estimation.
Onepot iridium catalyzed ch borylationsonogashira cross. This method represents a facile approach to synthetically useful. There are letters in the background so its easier to refer to the single steps in the text. 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. The sonogashira crosscoupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Modern fields use it such as with the construction of nanostructures chinchilla, 2007. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form.
Sonogashira reaction is the spsp2 carbon cross coupling reaction of terminal alkynes with aryl halides or alkenyl halide. An acetylene zippersonogashira reaction sequence for the. 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. In order to simplify the sonogashira reaction protocol, several important aspects have to be improved. Xingfeng bai department of chemistry, national university of singapore, 3 science drive 3, 117543 singapore, singapore. 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. Alternatively, you can download the file locally and open with any standalone pdf reader. The reaction of aryl halides or vinyl halides with terminal alkynes catalyzed by a pdiicui system is known as the sonogashira coupling, and.
This graphic shows the mechanism of the sonogashira coupling. Both the palladium precatalyst and ligand are commercially available, ben 2019 chemical science hot article collection 2019 chemsci pick of the week collection. 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. However, tolerance of aryl bromides to chb made possible a subsequent sonogashira crosscoupling to access the desired.
We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for an efficient template. Herein, we report on our findings of the sonogashirahagihara reaction with 1iodinated and 2brominated glycals using several aromatic and aliphatic alkynes. Sonogashira crosscoupling an overview sciencedirect topics. Aug 10, 2016 this video looks at the proposed mechanism for the sonogashira coupling reaction. 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. Exp 35 sonogashira coupling formal lab report chem 369. Alkynylsubstituted azoles represent important structural cores of several biologically active molecules 1 and organic functional materials. Carboncarbon coupling reactions via transitionmetalcatalyzed processes have been intensively developed for their important synthetic applications.
Highly regioselective c5 alkynylation of imidazoles by. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have. The sonogashira cross coupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. The sonogashira crosscoupling reaction has been employed in a wide variety of areas, due. Sonogashira coupling3 is versatile and has been applied to prepare several terminal and internal acetylenes. Pdf the coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium and other transition metals, commonly termed as sonogashira. 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. As early as 1975, heck 10, cassar 11 and sonogashira 12 independently discovered this reaction. Classification and properties of palladium catalysts. View enhanced pdf access article on wiley online library html view download pdf for offline viewing.
But the reaction is fraught with a limitation, in that it often results in considerable yields of hay coupling product homocoupling of terminal acet. 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. A variety of measurements indicate that aunanoparticle catalyzed sonogashira coupling of iodobenzene and phenylacetylene is predominantly a heterogeneous process. The alkynylation reaction of aryl halides using aromatic acetylenes was reported in 1975 in. Using spartan molecular modeling kit an explanation for the failure to employ analogues method in the synthesis of mtep was sought. Sonogashira coupling pdf uses of the sonogashira coupling. 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. This reaction is an extension to cassar and dieck and heck reactions, that carries coupling with the use of palladium catalyst. C bonds in academic as well as industrial communities. 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. People have used the glaser reaction to do this, they basically used a bis with dialkyne linkages. 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.
The application of the above reaction in a microflow system in conjunction with an imm micromixer was also successful. Palladiumcatalyzed sonogashira and hiyama reactions using. Pharmaceuticals free fulltext improved syntheses of. 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.
Pdf on jan 1, 2017, qing zhu and others published palladiumcatalyzed sonogashira coupling reaction of 2amino3bromopyridines with. Supported palladium catalysts are widely used in the suzuki, heck, and sonogashira crosscoupling reactions. 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 entire aqueous reaction medium can be easily recycled using an inflask extraction.
The use of an ionic liquid allows for the facile separation and recycling of the catalyst. The sonogashira crosscoupling reaction has been employed in a wide variety of areas. General procedure for sonogashira coupling reactions in a 4 ml screwcap vial, 0. Both of these reactions make use of a palladium catalyst to carry out. This video looks at the proposed mechanism for the sonogashira coupling reaction. Large gold particles are much more selective than small ones, consistent with this view. This pdcatalyzed crosscoupling reaction presents a facile access to alkynyl cglycosides.
Sonogashira coupling countable and uncountable, plural sonogashira couplings organic chemistry a crosscoupling reaction used in organic synthesis to form carbon carbon bonds. Sonogashirahagihara reactions of halogenated glycals. Sonogashira crosscoupling reaction is going to be used in a practical application. Sonogashira cross coupling reaction is going to be used in a practical application. 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. 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. As expected, the reaction of terminal alcohol 7 with 2iodothioanisole 9 proceeded slowly, and was accompanied by significant polymerization. This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copperi cocatalyst, and an amine. Nanoparticles derived from fecl3 containing the ligand xphos and only 500 ppm pd effect sonogashira couplings in water between rt and 45 c.
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. 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. Templatecontrolled sonogashira crosscoupling reactions. Synthesis and properties of arylnaphthylalkynes felix lederle, frederick meyer, christian kaldun, jan c.
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 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. Optimization of an efficient and sustainable sonogashira. You can look at example, conditions and references for sonogashira coupling in my recent book organic syntheses based on name reactions. We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for a. Rapid catalyst evaluation for sonogashira coupling in. Templatecontrolled sonogashira crosscoupling reactions on a. A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. Stille, suzuki, and sonogashira couplings crosscoupling.
We herein present a new catalytic system for the palladium. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important. Palladiumcatalyzed sonogashira coupling reactions in. Supported palladium catalysts are widely used in the suzuki, heck, and sonogashira cross coupling reactions. It is loosely based on the original publication of sonogashira in 1975 and the previous. 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. Simple, efficient copperfree sonogashira coupling of. What is the best procedure for sonogashira coupling. Sonogashira coupling catalyzed by gold nanoparticles. Palladiumcatalyzed phosphine, copperfree and aerobic.
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