Sonogashira reaction synthetic applications

In conclusion, the fantastically diverse chemistry of indole has been significantly enriched by palladium-catalyzed reactions. The accessibility of all of the possible halogenated indoles and several indolyl triflates has resulted in a wealth of synthetic applications as witnessed by the length of this chapter. In addition to the standard Pd-catalyzed reactions such as Negishi, Suzuki, Heck, Stille and Sonogashira, which have had great success in indole chemistry, oxidative coupling and cyclization are powerful routes to a variety of carbazoles, carbolines, indolocarbazoles, and other fused indoles. 

Aryl iodides, bromides, and inflates are used for Sonogashira coupling. But so far few smooth reactions of aryl chlorides with alkynes have been reported. On the other hand, smooth coupling takes place with alkenyl chlorides. The Pd-catalyzed reaction of 1-alkynes with alkenyl chlorides, which are inert in many other Pd-catalyzed reactions, proceeds smoothly without special activation of the chlorides. For example, cw-l,2-dichloroethylene (31) can be coupled with 1-alkynes smoothly, and the coupling has wide synthetic applications, particularly for the synthesis of enediyne structures [30]. The reaction of 31 with two different 1-alkynes is extensively used for construction of highly strained enediyne structures present in naturally occurring anticancer antibiotics such as espermicin and calichemicin [31,32]. The asymmetric (Z)-enediyne 34 can be prepared by a one-pot reaction of 31 with two different 1-alkynes 32 and 33. Similarly the asymmetric ( )-enediyne 37 was obtained in a one-pot reaction of 1-alkynes 33 and 23 with 1,2-dichloroethylene 35. 

Elegant synthetic applications of carbonylative Sonogashira reactions were described by Muller and his group. For example, in 2005 they succeeded in producing palladium-catalyzed one-pot, four-component carbonylations for the... 

In this chapter, we have discussed the carbonylative Sonogashira reaction of organohalides and their synthetic applications. Palladium-catalysts are still the main catalysts in this area. From the mechanism point of view, the same as the... 

K. Heuze, D. Mery, D. Gaus, D. Astruc - Chem. Commun., 2274,2003 Copper-free Monomeric and Dendritic Pd Catalysts for the Sonogashira Reaction Substituent Effects, Synthetic Applications, and the Recovery and Re-use of the Catalysts, Chem. Eur. J. 10,3936, 2004 ... 

There are numerous applications of the Sonogashira reaction in the solid phase synthesis of molecules of biological interest, in some cases as part of a synthetic sequence but in the majority of examples for scaffold diversification purposes, and only a few can be mentioned here. Takahashi and coworkers prepared a Ubrary of 96 cross-conjugated dienones by subjecting a pendant acetylenic moiety on a cyclopentenone scaffold, attached to polystyrene via the Ellman THP-linker, to a Sonogashira coupling reaction... 

Rhodium-catalyzed alkyne cyclotrimerization is also applicable to the synthesis of a polyalkyne substrate bearing ether-linked 1,6-diyne moieties 59, which is easily prepared by Pd-Cu-catalyzed Sonogashira couphng reactions. These reactions provide a novel and efficient synthetic route to oligophenylene 60, which bears benzodihydrofur-an moieties (Scheme 7.17) [40]. 

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