Sonogashira reaction in water at room temperature using. The regioselective sonogashira crosscoupling reaction performed on 2,4dihaloquinolines was achieved mainly by using different halides such as iodide and bromide, which drove to different reactivity. For the 2nd edition the complete text has been revised and updated, and four new reactions have been added. The most important improvement for the sonogashira coupling is probably to perform this reaction under copper. The optimum reaction time for 1pd was observed around 8 h, after which the percentage yield remained constant. This reaction has very broad application in the preparation of alkynes. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. Efficient sonogashira coupling reaction catalyzed by palladiumii. Organic letters sonogashira coupling reaction with. The sonogashira reaction also called the sonogashira hagihara reaction is the cross coupling of aryl or vinyl halides with terminal alkynes to generate conjugated enynes and arylalkynes scheme 1. Mechanism of copperfree sonogashira reaction operates. 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 reaction in water at room temperature using tpgs750m description tpgs750m, dl.
Mw irradiation is particularly efficient, awuah reported a homogeneous phase pd catalyzed copperfree procedure under less than an hour t 0. Results and discussion investigation of reaction conditions initially the coupling of 4iodoanisole and phenylacetylene was chosen as the model reaction for screening the reaction conditions. The complete mechanism for the sonogashira reaction is not completely understood because of the difficulty of isolating and analyzing the. The influences of different kinds of catalyst loading, bases. The sonogashira crosscoupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Pdf palladiumcatalyzed sonogashira coupling reaction of 2.
Sonogashira coupling pdf uses of the sonogashira coupling. The reaction typically proceeds in the presence of a palladium0 catalyst, a copperi cocatalyst, and an imine base. Sonogashira coupling reaction with diminished homocoupling. But the sonogashira reaction uses copper and palladium catalysts continuously. Despite many improvements to the original reaction, reports on generally applicable protocols that work under sustainable conditions are scarce.
The reaction of aryl halides or vinyl halides with terminal alkynes catalyzed by a pdiicui system is known as the sonogashira coupling, and. The sonogashira crosscoupling reaction has been employed in a wide variety of areas, due. 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. Summary the coupling of an aryl or vinyl halide with a terminal acetylene promoted by a palladium or other transition metal catalyst is. Terminal arylethynes, diarylethynes, and a few new arylpyridylethynes with donor substituents have been synthesized in very good yields. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds. The reactions conditions, mechanistic features and weaknesses of the sonogashira coupling have been discussed. Efforts to react perbenzylated 2chloro1iodoglucal 12 in a twofold sonogashira reaction with an excess of phenylacetylene resulted in a chemoselective monoalkynylation of the pseudoanomeric position in quantitative yield scheme 2. 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. Ligand, copper, and aminefree sonogashira reaction of. As expected, the reaction of terminal alcohol 7 with 2iodothioanisole 9 proceeded slowly, and was accompanied by significant polymerization. Copperfree sonogashira coupling reaction with pdcl in h o. The seminal contributions by sonogashira, cassar and heck in mid 1970s on pdcu and pdcatalysed copperfree coupling of acetylenes with aryl or vinyl halides have evolved in myriad applications.
The side product from homocoupling reaction of two terminal acetylenes in the sonogashira reaction can be reduced to about 2% using an atmosphere of hydrogen gas diluted with nitrogen or argon. The sonogashira coupling was proposed in the year 1975 by nobue hagihara, yasuo tohda and kenkichi sonogashira in their publication. A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. Turk j chem the next step of the synthesis of the 5 building blocks 3 involved a second sonogashira reaction between the bromoanthracene derivatives 2ae and tmsacetylene scheme 3. 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 sonogashira reaction is today the most versatile and powerful way to generate aryl alkynes, a moiety recurring in many pharmaceutical and natural products. Mechanism of copperfree sonogashira reaction operates through palladiumpalladium transmetallation article pdf available in nature communications 91 december 2018. As early as 1975, heck 10, cassar 11 and sonogashira 12 independently.
Optimization of the reaction conditions for the sonogashira reaction of iodobenzene with phenylacetylene. Mechanism of copperfree sonogashira reaction operates through. General procedure for sonogashira crosscoupling reaction arylhalide 1 mmol, triethylamine 1. Tocopherol methoxypolyethylene glycol succinate, is a designer surfactant composed of a lipophilic. Postsynthetic modified mof for sonogashira crosscoupling. The sonogashira reaction modern alkyne chemistry wiley. The sonogashira crosscoupling reaction was complete in five hours, giving product b in good yield table 2, entry 1. Sonogashira reaction of aryl and heteroaryl halides with terminal. Pdf on jan 1, 2017, qing zhu and others published palladiumcatalyzed sonogashira coupling reaction of 2amino3bromopyridines with. This reaction is one of the most effective methods to form new carboncarbon bonds 1 9. Further refunctionalization of the enynes was achieved by. Copperfree sonogashira crosscoupling reactions catalyzed. The exact mechanism of the palladiumcopper catalysed.
Palladiumcatalyzed sonogashira coupling reactions in. Scope and limitations of a dmf bioalternative within. Optimization of the catalyst loadings for the pdcucatalyzed sonogashira reaction. 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. The possible reuse of the catalyst was subsequently investigated by the model reaction of 0. Even the use of an elevated temperature did not lead to the formation of an enediyne.
Sonogashira crosscoupling reaction is going to be used in a practical application. 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 graphic shows the mechanism of the sonogashira coupling. Optimization of an efficient and sustainable sonogashira. S1 copperfree sonogashira coupling reaction with pdcl 2 in h 2o under aerobic conditions bo liang, mingji dai, jiahua chen and zhen yang, key laboratory of bioorganic chemistry and molecular engineering of ministry of education, college. It is loosely based on the original publication of sonogashira in 1975 and the previous. Palladiumcatalyzed sonogashira and hiyama reactions using. The sonogashira crosscoupling reaction has been employed in a wide variety of areas. Palladiumcatalyzed sonogashira coupling reaction of 2. Heterogeneous stille and sonogashira crosscoupling. The structure of target products 3a3u was confirmed and characterized by 1h nmr, c nmr, and hrms. People have used the glaser reaction to do this, they basically used a bis with dialkyne linkages. Rapid catalyst evaluation for sonogashira coupling in.
The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. Palladiumcatalyzed phosphine, copperfree and aerobic. 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. Sonogashirahagihara reactions of halogenated glycals. Effect of reaction time for sonogashira crosscoupling reactions of 1iodo4nitrobenzene and phenylacetylene using 1pd as catalyst. An acetylene zippersonogashira reaction sequence for the. Sonogashira reactions for the synthesis of polarized. The seminal contributions by sonogashira, cassar and heck in mid 1970s on pd cu and pdcatalysed copperfree coupling of acetylenes. 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. The reaction has become an essential tool in the synthesis of these compounds, which. Introduction sonogashira reaction is the spsp2 carbon crosscoupling reaction of terminal alkynes with aryl halides or alkenyl halide.
There are letters in the background so its easier to refer to the single steps in the text. The sonogashira reaction semantic scholar mafiadoc. 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 an indispensible tool for cc bond formation in the pharmaceutical industry 4. Sonogashira reaction is still at this moment not well understood. Pdf recent advances in sonogashira reactions rafael. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important.
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