Sonagashira Reaction

3-Bromoquinoline (70), behaving similarly to a simple carbocyclic aryl bromide, was coupled with phenylethyne 121 to provide disubstituted ethyne 122 in 50% yield (2001JCS(P1)978). 

The palladium-catalyzed reaction of o-iodoanilides with terminal acetylenic carbinols provides a facile route to the synthesis of quinolines using readily available starting materials (93TL1625). When o-iodoanilide 126 was stirred with acetylenic carbinol 127 in the presence of bis-triphenyl phosphine palladium(ll) chloride in triethylamine at room temperature for 24 h, the substituted alkynol 128 was obtained in 65% yield. On cyclization of 128 with sodium ethoxide in ethanol, 2-substituted quinoline 129 was obtained in excellent yield. 

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Negishi couplings (and Sonagashira reactions) also work for substitution in a 4-bromopyran-2-one <2003S2564>. 

There has been a theoretical study of the reaction of arenediazonium cations with azide anions, which yields arylazides. No evidence for the formation of arylpen-tazoles was found. Arenediazonium salts have been identified as intermediates in the palladium-catalysed Sonagashira reaction of arylamines with alkynes to give arylalkynes. Palladium catalysis has also been used in the synthesis of diarylheptanols by the reaction of 4-hydroxybenzenediazonium ions with dihydropyrans. ... 

Palladium(O) mediates the coupling of acetylenes and organoiodides in the Sonagashira reaction. 

Summary This is an exampie of the Sonagashira reaction which coupies an aikyne and an organohaiide under paiiadium cataiysis ... 

Heck, Stille, Suzuki, Sonagashira and Related Coupling Reactions... 

All these ethynylation reactions are particularly important since the common Sonagashira coupling does not allow ethynylpyrroles with strong electron-withdrawing substituents at the acetylenic fragments to be synthesized (99J(P1)2669). 

It is clear that [3 + 2] cyeloaddition chemistiy and Sonagashira eross-coupling reactions are powerful tools for the development of more complex CO-RMs and indeed other pharmaceutieals agents. Onee a suitable CO-RM has been developed there are thousands of possible interesting structures that ean then be attached on to the CO-releasing moeity. The cyclopentadienyl molybdenum tricarbonyl complexes shown in Scheme 3 could also be easily modified to give a eomplex with a terminal alkyne funetionality which would allow the same sort of chemistry to be carried out on those too. 

The Stille, Sonagashira, and Heck reactions can often be catalyzed by the addition of Pd(II) salts. However, we noted that Pd(0) is required to start these cycles. Triethylamine is often added to reduce the Pd(II). How does this reduction occur, and what is the mechanism ... 

Halodendralenes are valuable substrates for dendralene to dendralene transformations that preserve or extend the dendralene framework. They are intermediates in the synthesis of [7]- and [8]dendralene (Scheme 1.26) [23], as are their nucleophilic relatives, pinacolatoboryldendralenes, in the synthesis of substituted [4]-, [5]-, and [6] dendraienes [25, 27]. (Pseudo)halodendralenes have also been used in Stille [209] and Sonagashira cross-couplings [178, 210]. Dendralene dimers can be obtained via homocoupling of halodendralenes [211]. Dendralene frameworks can also be extended by uncatalyzed metathesis reactions on alkyne-containing dendraienes, and olefination reactions on carbonyl-containing ones [1, 211-214], each of which has been discussed. 

SCHEME 7.19 Synthesis of Aristolactam BII (cepharanone B), Aristolactam BIB, Aristolactam FI (piperolactam A), A-methyl piperolactam A and Sauristolactam. Sonagashira coupling reaction. 

The Sonagashira coupling reaction has become one of the most general, rehable and effective methods for the synthesis of substituted alkynes [40]. This reaction of terminal alkynes with aryl or vinyl halides is performed by using a palladium catalyst, a copper(I) cocatalyst, and an amine base. 

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