Acetylene surrogates

Nolan and co-workers reported on the coupling of arylbromides with TMS acetylenes making use of the imidazolium salt 34 in combination with Pd(OAc)2 and Cul. Slightly lower yields were obtained in the absence of the copper salt. Ag20 and Agl, instead of copper salts, have also been used with Pd(PPh3)4 for the coupling of aryl iodides with bis(TMS)alkynes and the coupling of vinyltriflates with a variety of alkynylsilanes, respectively. 

In addition to their use as precursors for alkynylboron, tin or zinc compounds, alkynylmagnesium reagents show a moderate reactivity toward the coupling with haloarenes and haloalkenes. They are often commercially available, or easy to prepare. Their main drawback is their low chemoselectivity and high nucleophilicity, which implies incompatibilities with functional groups such as nitro and carbonyl. 

An example of a non-palladium-based system was reported by Madec et al. They made use of Ni(PPh3)2Gl2 for the coupling of vinylcarbamates and alkynylmagnesium reagents in benzene at higher temperatures (70 °G), and obtained good yields of product.  

Lithium alkynyl(trialkoxy)borates have also been found suitable partners for this reaction, and have been success-fully coupled with aryl bromides, iodides, and allyl carbonates. Molander recently reported on the coupling of alkynyltrifluoroborates with aryl bromides, triflates, and chlorides in moderate yields using Pd(dppf)Gl2 as catalyst and GS2GO3 as base, in THF or water at 60 

Sonogashira protocol.The alkynylzinc reagent can also be prepared in situ form terminal alkynes by addition of ZnCl2 as a co-catalyst.  

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Mg acetylides are easily prepared and used for coupling. A good preparative method of 1-alkynes is the coupling of commercially available ethynylmagnesium chloride (122) or ethynylzinc chloride (123) as acetylene surrogates with aryl or alkenyl halides. Their couplings with halides directly afford the 1-alkynes 124. No deprotection is necessary [60]. 

High ee oxygenated secondary centers can also be prepared by homologation of aldehydes. Optimization of the enantioselective addition of the inexpensive acetylene surrogate 13 was recently reported (Chem. Commun. 2007, 948) by Masakatsu Shibasaki of the University of Tokyo. Note that the free alcohol of 13 does not need to be protected. 

Besides serving as a platform for the construction of the pyrrole ring (see Chapter 3.), the Sonogashira coupling is also effective in functionalising the same system. Trimethylsilylacetylene was used as a surrogate to introduce acetylene groups into the 2 and 5-positions of pyrrole (6.43.), 2,5-diiodo-... 

A convenient and simple method for the synthesis based on copper-catalyzed 1,3-dipolar cycloaddition of azidopeptides to acetylenes of tetrapeptide surrogates containing CF3-alkyl-l,2,3-triazolyl moiety 52 having ester of phosphonates functionalities or have been developed by Nenajdenko et al. [53, 54],... 

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