Sonogashira reaction derivatives, alkynylation

In contrast, an excellent yield was obtained for the reaction between 5-iodoimidazole and propargyl alcohol in the absence of Cul to install the 5-alkynyl derivative [10, 41], The adduct was then deprotected to 5-alkynyl- l-P-D-ribofuranosylimidazole-4-carboxamide 58, an antileukemic agent. It is noteworthy that if the Sonogashira reaction was conducted in the presence of Cul, the yield dropped to 19%. 

A plausible mechanism was proposed in Scheme 7.10. Firstly, 2- alkynyl-benzaldehydes 20 could be easily obtained via a Sonogashira reaction of 2-bromobenzaldehyde with alkyne. After condensation with sulfonohydrazide, N -(2-alk50iylbenzylidene)hydrazide I would be afforded. Subsequently, the 6-endo-cyclization would occur to generate the isoquinolinium-2-yl amide II in the presence of suitable Lewis acid. In this step, the formation of a p-complex via coordination of the alkynyl moiety of 20 to the Lewis acid would be involved, thus activating the triple bond for further cyclization. Meanwhile, die in situ formed enolate (derived from ketone or aldehyde in the presence of base) would attack the isoquinolinium-2-yl amide II to produce intermediate III. Subsequent intramolecular condensation and aromatization would give rise to the desired product 22. 

The ring expansion of oxyglycal-derived gm-dihalo 1,2-cyclopropanate oxyglycals provides stable seven-membered halo-oxepines, that are thus suitable precursors for further functionalizations. In a study, vinyl bromide of the bromo-oxepine was used for the metal-catalyzed cross-coupling reactions, namely, Heck, Suzuki, and Sonogashira reactions, so as to generate 2-deoxy-2-C-alkyl/ary/alkynyl septanosides [33]. 

The first example of an alkynylation of a bicyclic pyridazine derivative was published in 2000 [35]. Collins studied Sonogashira coupling of 7-bromo-6-[(1-methyl-l//-l,2,4-triazol-5-yl)methoxy]-3-phenyl[l,2,4]triazolo[4,3-Z ]pyridazine (165) with propargyl alcohol at 90°C in a sealed tube using Pd(PPh3)4 and Cul in triethylamine. Unfortunately, only a low yield of the reaction product (202) was obtained. 

Copper Reactants. 4-Alkynyl imidazoles are available from Al-protected 4-iodoim-idazoles and alkynes or alkynyltrialkyltin derivatives (Scheme 57). Reactions under Sonogashira conditions can be used to prepare the cross-coupled products 134. The same... 

With the development of Buchwald-Hartwig amination reactions, the amine component of these indoles can also be introduced into these precursors via palladium catalysis [8]. As shown by Ackermann, this can be coupled with aryl halide alkynylation and cyclization to provide a one-pot, three-component synthesis of substituted indoles (Scheme 6.6) [9]. In this case, simple ortho-dihaloarene derivatives S were employed as starting materials, with Sonogashira coupling occurring at the more activated aryl-iodide bond, followed by selective coupling of various alkyl or arylamines. Alternatively, Zhao has recently demonstrated that amination can be performed on both bromoalkyne 6, followed by the aryl-bromide bond, to provide a route to 2-amidoindoles (Scheme 6.7) [10]. 

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