Sonogashira reaction pyrroles

The Sonogashira reaction frequently serves as a platform for the construction of indoles, and we will explore this application in Chapter 3, but it also is a valuable method for the preparation of alkynyl pyrroles. 

More recently, Lautens has also employed l-(2-iodophenyl)-pyrrole as a bifunctional aryl iodide/acceptor for the synthesis of substituted pyrrolo[l,2]quinolines (Scheme 34)[82], During Catellani s application of the Cassar-Sonogashira reaction to the ort/m-alkylation sequence [70] it was found that alkynes can undergo further carbopalladation reactions with arylpalladium(II) species. It was this reactivity which led Lautens to explore the use of bromoalkylalkynes as species which can undergo an ort/zo-alkylation, followed by a cyclocarbopalladation onto the alkyne,... 

Some drawbacks of the precursor routes mentioned above have been overcome by the use of polycondensation- and C-C-bond-coupling reactions. To produce soluble PPV-, poly(thiophene)-, or poly(pyrrol) derivatives for spin coating preparation, various types of transition metal catalyzed reactions, such as the Heck-, Suzuki-, and Sonogashira-reaction, Wittig- and Wittig-Horner-type coupling reactions, or the McMurry- and Knoevenagel-condensation have been utilized. 

The Sonogashira reaction with TMSA could also be succes-fully accomplished in the coupling with different heteroaryles such as pyrroles, thiophenes, pyrimidines, purines, and quinazolines. ... 

The bromine atoms in 2,5-dibromo-l,3,4-thiadiazole 54 undergo a palladium-catalyzed Stille reaction with the organostannyl derivative 55 (Equation 7) <1998CEJ2211>. The thiadiazole 54 was co-polymerized with diethynyl benzene 56 (Equation 8) and diethynyl pyrrole in a Sonogashira cross-coupling reaction <2005MM4687>. 

In conclusion, the already rich chemistry of pyrroles is greatly expanded by the palladium reactions presented in this chapter. The abundance of both 2- and 3-pyrrolyl halides and triflates has led to many examples of high-yielding Negishi, Suzuki, Stille, Sonogashira, and Heck reactions. Noteworthy are the excellent approaches to alkynyl pyrroles and porphyrins using Sonogashira, Stille, and Suzuki reactions. 

Duchene and Parrain developed a one-pot allylic amina-tion/palladium-catalyzed Sonogashira cross-coupling and heterocyclization process for the preparation of 1,2,4-trisub-stituted and 1,3-disubstituted pyrroles starting from diiodo-butenoic acid, a primary amine, and a terminal alkyne [49], Scheme 3.27 shows a plausible mechanism for this transformation. The initial C—N allylic amination, followed by a Sonogashira cross-coupling and an intramolecular hydroam-ination, affords a dihydroexoalkylidene pyrrole XIX, which rearranges into pyrrole 39. The reaction is influenced by the... 

S. Lamande-Langle, M. Abarbri, J. Thibonnet, A. Dnchene, J.-L. Parrain, Chem. Commun. 2010,46,5157-5159. Domino allylic amination/Sonogashira/heterocyclisation reactions palladium-catalysed three-component synthesis of pyrroles. 

Transition-metal-mediated C—X bond formation by intramolecular reactions with alkynes is a powerful strategy for the construction of heteroarene rings such as pyridines, pyrroles, and furans. Because of the wide availability of Sonogashira coupling of various haloarenes with terminal alkynes, these transformations provide efficient routes to synthesize fused heteroarenes, including isoquinolines, indoles, and benzofurans. In this chapter the construction of aromatic rings by transition-metal-catalyzed or transition-metal-mediated intramolecular C—X bond formation between C—X or X—H and alkynes is described. As shown in Scheme 19.1, Section... 

In 1980, Ames et al. reported a related pyrrole formation catalyzed by mer-cury(II) [98], Pyrrole-fused quinoxaline 204 was obtained by treatment of a 2-amino-3-alkynylquinoxaline derivative 203 with a catalytic amount of Hg(OAc)2 (Scheme 19.53). On the other hand, dichloroquinoxaline 205, the precursor of 203, was converted directly to 204 under reaction conditions for Sonogashira coupling with phenylacetylene. A related palladium(II)-catalyzed pyrrole synthesis using 1-aminoalk-3-yn-2-ols 206 was reported by Utimoto, Nozaki and co-workers in 1981 (Scheme 19.54) [99]. It should be noted that PdCl2 showed excellent turnover to produce the corresponding pyrroles 207 in good yields with only 0.1 to 1 mol % catalyst loading. 

The discussed variants of novel ethynylation of the pyrrole nucleus look even more attractive taking into account that the standard transition metal-catalyzed reactions, including the Sonogashira cross-coupling, do not allow the ethynylpyrroles with electron-withdrawing functions in acetylene substituent to be synthesized [525]. 

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