Aqueous conditions Sonogashira reaction

Removal of the tri-wo-propylsilyl (TIPS) and tm-butyldimethylsilyl (TBS) protecting groups could be accomplished concomitantly with TBAF in tetrahydrofuran at 0 °C, but here competing elimination of the secondary bromide was observed. Better overall yields and cleaner conversion was observed when TBS ether was cleaved with 5 % aqueous HF in acetonitrile at 0 °C followed by removal of the acetylenic TIPS with TBAF under milder conditions of -78 °C.10 The diastereomers are not separated before the desilylation process therefore even a 3 1 mixture of E- and Z-enyne is obtained. Prelaureatin 4 and its F-isomer 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the alkyne is introduced via a Sonogashira reaction. 

As was demonstrated with the Suzuki reaction [57], aqueous reaction conditions could be applied to the Sonogashira reaction and have also been investigated, but required changing the nature of the palladium ligand. Alkynylpyridine 324 was prepar ed by crosscoupling 26 with 323. 

It was also found that the Sonogashira reaction [69] takes place under aqueous alkaline conditions in the presence of the PS-PEG-supported palladium complex 59 [95]. The combination of the resin catalyst 59, cesium hydroxide [96], and water is essential to promote high yielding coupling of 69. Using copper-free conditions, a one-step preparation of the benzofurans 70 was achieved in water via coupling of 2-iodophenol 68 (X=OH) and the terminal alkynes (Scheme 23). 

Some of the optimized procedures for Stille and Sonogashira reactions involve the addition of copper cocatalysts to accelerate the cross-coupling procedures. A word of caution should be provided on the role of these additives in Pd-catalyzed amination procedures. Beletskaya and Davydov have reported the arylation of benzotriazole and of diary-lamines in polar organic or aqueous organic solvents using a combination of palladium and copper as catalyst.The arylation of amino acids has been reported under similar conditions.However, these reaction conditions are similar to classic Ullmann procedures for the synthesis of arylamines, except for the addition of palladium to the reaction mixture. In one case, subsequent work showed that the palladium species was not an essential component and that copper alone was the true catalyst in their reactions. An unusual accelerating effect of amino acid coordination to copper was used to explain the low-temperature Ullmann conditions. Beletskaya, however, showed that lower yields and a mixture of N1 and N2 arylation products were observed from the reactions of benzotriazole in the absence of copper and no reaction was observed in the absence of palladium. The conditions for this chemistry are, however, distinct enough from those of the majority of the aryl halide aminations to support the idea that a different mechanism may operate. 

---