Sonogashira reaction conditions

In 1987, Yamanaka s group described the Pd-catalyzed reactions of halothiazoles with terminal acetylenes [22a]. Submission of 4-bromo- and 5-bromo-4-methyloxazoles to the Sonogashira reaction conditions with phenylacetylene led to the expected internal acetylenes. 

The standard Sonogashira reaction conditions were not successful for the coupling reaction of 3-chloropyrazine 1-oxide (40) and 1-hexyne. In contrast, treatment of 40 and 1-hexyne with Pd(Ph3P)4 and KOAc produced 3-(l-hexynyl)pyrazine 1-oxide (41), together with the co-dimeric product, (E)-enyne 42 [34]. Presumably, the co-dimerization product 42 resulted from the cis addition of 1-hexyne to adduct 41. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. Heteroaryl halides like bromooxazoles are viable substrates for the Pd-catalyzed cross-coupling reactions with terminal acetylene in the presence of Pd/Cu catalyst. In 1987, Yamanaka s group described the Pd-catalyzed reactions of halothiazoles with terminal acetylenes [50]. Submission of 4-bromo- (72) and 5-bromo-4-methyloxazoles (73) to the Sonogashira reaction conditions with phenylacetylene led to the expected acetylenes (74 and 75). 

The Sonogashira reaction allows for the direct cross-coupling of terminal alkynes with aryl halides under mild conditions through use of catalytic bis(triphenylphosphine)-palladium dichloride and Cul as the co-catalyst in the presence of an aliphatic amine. The formation of diphenylacetylene exemplifies the original Sonogashira reaction conditions ... 

STR) that led to the identification of the alkyne linker as the key motif responsible for serious neurological and cardiovascular liabilities in a class of acetyl-CoA carboxylase 2 (ACC2) inhibitors. To study this toxicity, the alkyne derivatives were prepared by first employing the Sonogashira reaction conditions shown below, followed by deprotection of the phthalimide group. 

Under Sonogashira reaction conditions, the propensity of terminal alkynes to form dimerized products (15) is often attributed to oxidation of... 

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