Sonogashira coupling reaction conditions

Based on these results, conditions for alkyl-Sonogashira coupling reactions were developed. Primary alkyl halides reacted with terminal alkynes catalyzed by 5 mol% of complex 24a and Cul in the presence of substoichiometric amounts of Nal for bromides or Bu4NI for alkyl chlorides (entry 29) [73]. The latter serves to catalyze the in situ generation of more reactive alkyl iodides under the reaction conditions. The internal alkyne products were isolated in 57-89% yield. The Sonogashira coupling can also be combined to the Kumada reaction described above. a,o)-Chloroalkyl bromides underwent the Kumada coupling first selectively... 

The same researchers reported that a 2-hydroxymethyl protecting group (208) is compatible with Sonogashira cross-coupling reaction conditions [76, 89]. Remarkably, using this protective group, alkynylation occurs first followed immediately by the loss of formaldehyde (deprotection) via a base or heat promoted retro-ene reaction. 

The Sonogashira coupling reaction of aryl halides were attached to a PEG matrix as para-substituted benzoates was also reported [128]. It was shown that MW irradiation can reduce the reaction time from 3 h under conventional conditions to 1.5 min, and that yields of the products were approximately the same. Similarly, the cleavage proceeded faster under MW conditions (1 min compared with 5 h at 50 °C under conventional conditions). 

The first report of a Sonogashira coupling reaction of an oxazole was by Yamanaka in 1987. Oxazoles substituted with bromine at the 4- or 5-positions were coupled with phenylacetylene yielded the alkyne in 83% and 89% yield, respectively. The Sonogashira reaction with 2-halooxazoles was not attempted however, 2-halothiazoles and 2-halo-A -methylimidazoles were subjected to Sonogashira conditions. Yields in both cases were low and not synthetically useful. 

Another example of carbonylative Sonogashira coupling reactions with iodi-nium iodide and 1-alkynes was published by Ma and colleagues in 2001 [32]. Under mild conditions, iodine-substituted alkynones were produced in good yields (Scheme 5.9). Both aromatic, aliphatic and heterocyclic terminal acetylenes can be applied as their substrates. 

After using a one-pot Larock indolization-Sonogashira coupling reaction and subsequent nitro-group reduction to assemble the requisite alkynyl aminoindole, Au(I)-catalyzed intramolecular hydroamination can be used in a key step to prepare (-l-)-terreusinone (Scheme 15.126) [374]. Efforts to assemble this product using a double Larock indolization were unsuccessful, despite attempting a broad range of reaction conditions. 

Liang B, Dai M et al (2005) Copper-free Sonogashira coupling reaction with PdCl in water under aerobic conditions. J Org Chem 70 391-393... 

By the combination of two consecutive Sonogashira coupling reactions, the synthesis of internal alkynes, such as bisaryl-alkynes and arylalkenyl-alkynes, can be achieved. Because the terminal silyl group is inert to further coupling under the standard Sonogashira conditions, it must be removed prior to the second coupling step by common methods (e.g., TBAF or basic conditions eq 17).34... 

Similar to the Sonogashira and related sp-sp couplings, there are no regio-or stereoselectivity complications in the Castro-Stephens coupling. Reaction conditions are quite vigorous, however, and where vinyl halides with defined geometry are used, the potential for olefin scrambling must be considered because there are rare cases where olefin isomerisation has been observed. ... 

Analogous intermolecular one-pot cascade transformation has been developed by Xi et al. [11b]. Consequently, a-bromoacrylates reacted with terminal acetylenes with the formation of densely substituted styrenes in a single transformation under Sonogashira cross-coupling reaction conditions (Scheme 14.14). This method was efficient for both aryl or alkyl acetylenes. Among vinyl bromides, only acrylate derivatives were shown to produce styrene derivatives in good yields. 

The homocoupling of all yl-aryl halide monomers was carried out by Trumbo, D. L. Marvel, C. S. J. Polym. ScL, Polym. Chem. Ed. 1986,24,2311. The alkynyl cross-coupling reaction conditions employed were developed by Takahashi, S. Kurqyama, Y. Sonogashira, K Hagihara, N. Synthesis 1980,627. 

Concerning other metals, Sonogashira coupling products have also been observed in the reaction of Ag(l)-carbenes [133] and Au(I)-supported carbenes [134] in low to moderate yields, but only under harsh conditions (more than 100°C). In this regard, NHC based catalysts for Sonogashira reactions have been supported on different materials that include clays [135], polymers [136] and peptides [137]. 

---