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. Palladiumfree sonogashiratype crosscoupling reaction of. The formed alkynone motive serves as a platform for synthesis of various heterocyclic structures, including pyrimidines. Ligand, copper, and aminefree sonogashira reaction of aryl iodides and bromides with terminal alkynes sameer urgaonkar and john g. Desulfitative sonogashiratype crosscoupling the desulfitative sonogashiratype. Handbook oforganopalladium chemistry for organic synthesis,vol. Systems in which the reaction proceeds without palladium or copper are beginning to emerge in recent years. To develop a copperfree catalytic system, we attempted to use an experimental design tool.
Specifically, employing orthoamino 5 or ortho hydroxyaryl iodides 6 in the sonogashira process generated analkyne intermediate that, upon increasing the reaction. The sonogashira crosscoupling reaction has been employed in a wide variety of areas, due. Excellent yields were obtained at ppm levels not greater than 50 in most cases. Both of these reactions make use of a palladium catalyst to carry. 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 researchgate. Sonogashira crosscoupling an overview sciencedirect. This video looks at the proposed mechanism for the sonogashira coupling reaction. Ligand, copper, and aminefree sonogashira reaction of. This graphic shows the mechanism of the sonogashira coupling. The use of 1 mol % pdcl2 in the presence of pyrrolidine allows the coupling reaction to proceed at room temperature or 50 c with good to excellent yields. You can look at example, conditions and references for sonogashira coupling in my recent book organic syntheses based on name reactions.
Modified and efficient sonogashira coupling reaction tactic has been developed for the functionalization of quinoline motif at different position. 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 cross coupling reaction between an aryl or alkyl halide and a terminal alkyne catalyzed by the combination of pd0, copper iodide, and an amine is called the sonogashirahagiwara reaction. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. The reaction of aryl halides or vinyl halides with terminal alkynes catalyzed by a pdiicui system is known as the sonogashira coupling, and. 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. A general procedure for the palladiumcatalyzed carbonylative sonogashira coupling of aryl bromides is reported, using near stoichiometric amounts of carbon monoxide.
People have used the glaser reaction to do this, they basically used a bis with dialkyne linkages. Alternatively, you can download the file locally and open with any standalone pdf reader. Efficient suzuki and sonogashira coupling reactions catalyzed by. The reaction is carried out in two steps under standard sonogashira coupling conditions from an n substituted n,n disubstituted 2 iodoaniline and a terminal alkyne, followed by the addition of acetonitrile and an aryl iodide. In order to simplify the sonogashira reaction protocol, several important aspects have to be improved. Empowering a transition metalfree coupling between alkyne and alkyl iodide with light in water. Sonogashira coupling catalyzed by palladium on polymer. 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. Mechanism of copperfree sonogashira reaction operates. The ease of isolating and purifying these precursors has enabled numerous thiophenebased compounds to be synthesized from building blocks with widely different characteristics.
Following the deprotection of the acetylene moiety in the same pot using a strong base, the sonogashira coupling of a second. Pdcatalyzed crosscoupling reactions using organotins stille coupling 43 and organoborons suzuki coupling 44. Sonogashira coupling reaction with diminished homocoupling arumugasamy elangovan, yuhsiang wang, and tonging ho department of chemistry, national taiwan university, taipei 106, taiwan r. The sonogashira crosscoupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Sonogashira coupling of 5 and 7bromoquinolines with alkynes in the presence of palladium0 and copperi iodide gives alkynylsubstituted quinolines in good yield. Organic letters sonogashira coupling reaction with. A microwaveassisted, onepot, threecomponent coupling reaction for the synthesis of indoles has been developed. A mild protocol for the copperfree sonogashira coupling of aryl iodides with terminal acetylenes in water under aerobic conditions has been developed. 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. Occasionally, this reaction is also referred to as the sonogashirahagihara reaction. Palladiumcatalyzed phosphine, copperfree and aerobic. What is the best procedure for sonogashira coupling.
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 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 coupling was proposed in the year 1975 by nobue hagihara, yasuo tohda and kenkichi sonogashira in their publication. Pdf rapid catalyst evaluation for sonogashira coupling. Sonogashira couplings catalyzed by fe nanoparticles. Therefore, this reaction is generally known as the sonogashira coupling. In spite of wide applications of pdcatalysts in coupling reaction, the catalyst recovery and. Optimization of an efficient and sustainable sonogashira. Palladium and copper cocatalyzed sonogashira coupling is reported to proceed via two independent catalytic cycles scheme 2. Mohammad bakherad, ahmad kakav ghalenoei, ali keivanloo. Supported palladium catalysts are widely used in the suzuki, heck, and sonogashira crosscoupling reactions.
The best yield in the shortest reaction time was obtained with tungsten carbide ball. The original catalytic system for sonogashira couplings include the use of a palladium catalyst and a. The sonogashira cross coupling reaction was first reported by kenkichi sonogashira, yasuo tohda, and nobue hagihara in their 1975 publication. Synthesis of 4substituted6methyl2methylthiopyrimidines catalyzed by pdcu. Simple, efficient copperfree sonogashira coupling of. Metal catalyzed sonogashira coupling reaction is a heterogeneous process. The factorial design is a useful analytical strategy, whose main application is the screening of relevant variables of a given system. Scope and limitations of a dmf bioalternative within. The tandem sonogashira coupling reaction of aryl halides provides an efficient method for the synthesis of diarylalkynes. 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. The entire aqueous reaction medium can be easily recycled using an inflask extraction.
A ligandfree solidsupported system for sonogashira couplings core. In addition to the suzuki coupling of aryl chlorides and. Sonogashira crosscoupling an overview sciencedirect topics. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form carboncarbon bonds. 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. 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. Stille, suzuki, and sonogashira couplings crosscoupling. Rapid catalyst evaluation for sonogashira coupling in. Palladiumcatalyzed the sonogashira coupling reaction of. Use of rutheniumalumina as a convenient catalyst for copperfree sonogashira coupling reactions. Several tandem processes in one pot are illustrated, including a sequence involving five steps 10 reactions in good overall yield.
Several aryl halides were coupled with 2methyl3butyn2ol as acetylene source in the presence of pdcl2pph32 and cui. Heck reaction and sonogashira coupling while frechs catalyst demonstrates high activity with just 0. A brief introduction to the history and development of sonogashira coupling will be presented. The method allows a broad substrate scope in moderate to excellent yields. It is loosely based on the original publication of sonogashira in 1975 and the previous. The sonogashira reaction is a crosscoupling reaction used in organic synthesis to form. Sonogashira coupling, continuous flow, microreactor, immobilized catalysts, catalyst screening introduction pdcatalyzed sonogashira coupling is currently the most practical method for synthesizing arylvinyl acetylenes from the corresponding terminal alkynes and aryl halides. Nanoparticles derived from fecl3 containing the ligand xphos and only 500 ppm pd effect sonogashira couplings in water between rt and 45 c. Pd as a catalyst, cu as cocatalyst and an amine as a base. 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%. Sonogashira coupling pdf uses of the sonogashira coupling. Heck coupling pdcatalyzed coupling between aryl or vinyl halides with activated alkene in basic media.
The reaction has become an essential tool in the synthesis of these compounds, which. Use of rutheniumalumina as a convenient catalyst for. Direct borylation of aryl alkynes encountered problems related to the reactivity of the alkyne under chb conditions. 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. An efficient, microwaveassisted, onepot synthesis of. Occasionally, this reaction is also referred to as the sonogashira hagihara reaction. Heck and sonogashira couplings in aqueous media application to. Sonogashira coupling terminal alkynes with aryl or vinyl halides triflate. Metal catalyzed sonogashira coupling reaction is a. The reactions conditions, mechanistic features and weaknesses of the.
Mechanism of copperfree sonogashira reaction operates through. The seminal contributions by sonogashira, cassar and heck in mid 1970s on pd cu and pdcatalysed copperfree coupling of acetylenes. Copperfree sonogashira coupling reaction with pdcl2 in. Onepot iridium catalyzed ch borylationsonogashira cross. The palladium catalyzed mechanism begins with oxidative addition of the organohalide to the pd0 to form a pdii complex. Palladiumcatalyzed carbonylative sonogashira coupling of. Sonogashira coupling project gutenberg selfpublishing. There remained, however, a need to develop reaction conditions for the coupling of haloaryl. However, tolerance of aryl bromides to chb made possible a subsequent sonogashira crosscoupling to access the. The sonogashira crosscoupling reaction has been employed in a wide variety of areas. Pdf palladiumcatalyzed sonogashira coupling reaction of 2. 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. Empowering a transitionmetalfree coupling between alkyne. Catalytic cycle of palladium and copper cocatalyzed sonogashira reaction. A lot of times with sonogashira reactions you will get defects from the homo coupling of two alkyne groups. Pdf the coupling of aryl or vinyl halides with terminal acetylenes catalysed by palladium.