The influences of different kinds of catalyst loading, bases. 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. Sonogashirahagihara reactions of halogenated glycals. The reaction typically proceeds in the presence of a palladium0 catalyst, a copperi cocatalyst, and an imine base. 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. The complete mechanism for the sonogashira reaction is not completely understood because of the difficulty of isolating and analyzing the. Scope and limitations of a dmf bioalternative within. Sonogashira crosscoupling reaction is going to be used in a practical application. The sonogashira reaction is today the most versatile and powerful way to generate aryl alkynes, a moiety recurring in many pharmaceutical and natural products.
Summary the coupling of an aryl or vinyl halide with a terminal acetylene promoted by a palladium or other transition metal catalyst is. Optimization of an efficient and sustainable sonogashira. Rapid catalyst evaluation for sonogashira coupling in. The sonogashira crosscoupling reaction has been employed in a wide variety of areas, due. General procedure for sonogashira crosscoupling reaction arylhalide 1 mmol, triethylamine 1. Sonogashira coupling reaction with diminished homocoupling. Palladiumcatalyzed phosphine, copperfree and aerobic. 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 reaction modern alkyne chemistry wiley. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds.
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. Tocopherol methoxypolyethylene glycol succinate, is a designer surfactant composed of a lipophilic. 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. 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. A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. Optimization of the catalyst loadings for the pdcucatalyzed sonogashira reaction. The seminal contributions by sonogashira, cassar and heck in mid 1970s on pd cu and pdcatalysed copperfree coupling of acetylenes. The reaction of aryl halides or vinyl halides with terminal alkynes catalyzed by a pdiicui system is known as the sonogashira coupling, and. 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. Postsynthetic modified mof for sonogashira crosscoupling. 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. But the sonogashira reaction uses copper and palladium catalysts continuously. As early as 1975, heck 10, cassar 11 and sonogashira 12 independently.
Sonogashira reactions for the synthesis of polarized. The exact mechanism of the palladiumcopper catalysed. The reactions conditions, mechanistic features and weaknesses of the sonogashira coupling have been discussed. Sonogashira reaction of aryl and heteroaryl halides with terminal. The optimum reaction time for 1pd was observed around 8 h, after which the percentage yield remained constant. 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. Palladiumcatalyzed sonogashira coupling reaction of 2. Mw irradiation is particularly efficient, awuah reported a homogeneous phase pd catalyzed copperfree procedure under less than an hour t 0. It is loosely based on the original publication of sonogashira in 1975 and the previous. Even the use of an elevated temperature did not lead to the formation of an enediyne. This graphic shows the mechanism of the sonogashira coupling.
Copperfree sonogashira coupling reaction with pdcl in h o. The sonogashira crosscoupling reaction was complete in five hours, giving product b in good yield table 2, entry 1. Mechanism of copperfree sonogashira reaction operates through palladiumpalladium transmetallation article pdf available in nature communications 91 december 2018. 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.
Copperfree sonogashira crosscoupling reactions catalyzed. Palladiumcatalyzed sonogashira and hiyama reactions using. Efficient sonogashira coupling reaction catalyzed by palladiumii. The sonogashira crosscoupling reaction has been employed in a wide variety of areas. The sonogashira coupling was proposed in the year 1975 by nobue hagihara, yasuo tohda and kenkichi sonogashira in their publication. Mechanism of copperfree sonogashira reaction operates through. The sonogashira crosscoupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication.
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. Sonogashira reaction in water at room temperature using. An acetylene zippersonogashira reaction sequence for the. Organic letters sonogashira coupling reaction with. 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. Terminal arylethynes, diarylethynes, and a few new arylpyridylethynes with donor substituents have been synthesized in very good yields. Optimization of the reaction conditions for the sonogashira reaction of iodobenzene with phenylacetylene. 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. Effect of reaction time for sonogashira crosscoupling reactions of 1iodo4nitrobenzene and phenylacetylene using 1pd as catalyst. The sonogashira reaction semantic scholar mafiadoc. There are letters in the background so its easier to refer to the single steps in the text. 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. 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.
The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. The structure of target products 3a3u was confirmed and characterized by 1h nmr, c nmr, and hrms. The most important improvement for the sonogashira coupling is probably to perform this reaction under copper. Pdf palladiumcatalyzed sonogashira coupling reaction of 2. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important. The possible reuse of the catalyst was subsequently investigated by the model reaction of 0. Pdf on jan 1, 2017, qing zhu and others published palladiumcatalyzed sonogashira coupling reaction of 2amino3bromopyridines with. Ligand, copper, and aminefree sonogashira reaction of. For the 2nd edition the complete text has been revised and updated, and four new reactions have been added.
As expected, the reaction of terminal alcohol 7 with 2iodothioanisole 9 proceeded slowly, and was accompanied by significant polymerization. Further refunctionalization of the enynes was achieved by. 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 enynes or aryl alkynes. Despite many improvements to the original reaction, reports on generally applicable protocols that work under sustainable conditions are scarce. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. This reaction is an extension to cassar and dieck and heck reactions, that carries coupling with the use of palladium catalyst. Sonogashira reaction in water at room temperature using tpgs750m description tpgs750m, dl. A potential intermediate species of the reaction, corresponding to a copper cluster linked with acetylide moiety, has been identified. Sonogashira reaction is still at this moment not well understood. This reaction has very broad application in the preparation of alkynes.
Mechanism of copperfree sonogashira reaction operates. Sonogashira coupling pdf uses of the sonogashira coupling. Palladiumcatalyzed sonogashira coupling reactions in. 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. Pdf recent advances in sonogashira reactions rafael.
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