Regioselectivity Sonogashira reaction

Alkynylfurans are readily prepared via the Sonogashira reactions of halofurans [66, 67]. Due to activation of the a-positions, regioselective Sonogashira reaction can be achieved at C(2) rather than C(3) [35,68]. 

Van der Eycken s group developed a silver(I)-mediated synthesis of substituted furo[2,3-6]pyrazines.53 Starting from -methoxybenzyl-protected 3,5-dichloropyr-azine-2(l//)-ones 26 (Scheme 5.13), after a regioselective microwave-assisted Sonogashira reaction with various terminal alkynes, the cycloisomerization reaction could occur using AgOTf (2 mol%) with trifluoroacetic acid (TFA, 5 equiv) to yield... 

The regioselective coupling reaction of 2,3-dibromobenzo[/ ]furan with several terminal acetylenes was achieved using a palladium-catalyzed Sonogashira reaction, as exemplified in Equation (91) <2003S925>. 

However, in this case the electron-rich 1-methoxypropyne was used as the monoalkyne. First, 108 was converted into yne-ynamide 109 by three steps, including a Sonogashira reaction with trimethylsilylacetylene and the ynamide formation based on the alkynyliodonium salt 105. Yne-ynamide 109 was then alkylated with iodopen-tane, and subsequent desilylation with TBAF provided the diyne 110 (44% yield over two steps). The key cyclotrimerization of diyne 110 with 1-methoxypropyne was carried out in toluene at room temperature in the presence of 10 mol % of Wilkinson s catalyst and afforded chemo- and regioselectively carbazole 111 (82% yield, isomer... 

Dichloro- and 3,5-dibromoisothiazole-4-carbonitriles 285a/b undergo regioselective Stille, Negishi, Sonogashira coupling reactions at C-5 to provide 3-halo-5-substituted... 

As previously discussed, the Pd-catalyzed reactions of 2,5-dibromopyridine including Sonogashira, Negishi, and alkoxycarbonylation all take place at C(2). It has also been demonstrated that aminocarbonylation of 2,5-dibromo-3-methylpyridine occurred regioselectively at C(2) to afford 196 despite the steric hindrance of the 3-methyl group [157]. 

As shown in Equation (37), 4,5-dibromo-2-furaldehyde and methyl 4,5-dibromo-2-furoate underwent regioselective cross-coupling reaction at the 5-position with alkynes under Sonogashira-type conditions, presumably due to the activation of the 5-position by the electron-withdrawing groups at the 2-position toward oxidative palladium insertion <1998TL1729, 1999EJO2045>. 

As with thiophene, 2,3-dibromobenzo[/ ]thiophene also exhibits a high regioselectivity in coupling reactions <2005T2245>. For example, Sonogashira coupling with /-butylacetylene leads exclusively to the 3-bromo derivative 90. 2,3-Unsymmetrically substituted derivatives of benzo[/ ]thiophene can be obtained by two successive crosscoupling reactions (Scheme 18). 

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