Aryl halides with terminal alkynes

Wang, J.X., Liu, Z.X., Hu, Y.L., Wei, B.G. and Kang, L.Q., Microwave-assisted copper catalysed coupling reaction of aryl halides with terminal alkynes, Synth. Commun., 2002, 32, 1937-1945. 

RXN67 Intermolecular Tandem Carbonylation-Coupling-Cyclization Process of Aryl Halides with Terminal Alkynes... 

A convenient catalyst system, consisting of [Pd(OAc)2] and PPhs in dimethyl-sulfoxide (DMSO) as solvent and K3PO4 as base was recently reported [14], and found to be effective for the coupling of aryl halides with terminal alkynes. Among various ligands tested, an iminophosphine ligand gave (in some cases) better conversions than when PPhs was employed. 

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42]. This methodology is now used widely for the constiuction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modem acetylene chemistry [44]. 

Okuro, K., Furuune, M., Miura, M., Nomura, M. Copper-catalyzed coupling reaction of aryl and vinyl halides with terminal alkynes. 

The molecular turnstile was synthesized by regioselective and sequential palladium-catalyzed cross-coupling reactions between aryl halides and terminal alkynes [32]. The successful strategy incorporates the spindle in the first step of the synthesis and the last step is a macrocyclization. Three molecular systems (12-14) with different spindles have been prepared. The compounds, particularly 12 and 13, show low solubility, perhaps due to their relative planarity. 

A solvent-free variant used octahedral CU2O nanoparticles with added PPhj ligand, which effectively catalyzed the cross-coupling reactions of various aryl and heteroaryl halides with terminal alkynes [148]. The catalyst was reusable without any observable loss of activity, but worked only at temperatures above 100 °C. Further improvements to this approach involved the elimination of the Hgand and carrying out the reaction in a mixture of DMSO, K2CO3, and catalytic amounts of CU2O nanoparticles [149]. 

On the other hand, Suzuki and co-workers have demonstrated that copper(I) species can promote the reaction of vinyl halides with terminal alkynes without the need for a palladium catalyst however, as in the Castro reaction, a stoichiometric amount of copper salt is needed. By contrast, Miura and coworkers found that aryl and vinyl iodides smoothly react with terminal alkynes in the presence of a catalytic amount of copper iodide using potassium carbonate as base when an appropriate amount of triphenylphosphine is added. Pyridine or 1,2-bis(diphenylphosphino)ethane (dppe) have been used as ligands in the case of Cul-catalyzed reaction of terminal alkynes with nitrones. ... 

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl halides with ethynylmetals, formation of diarylethynes is one of the potential side reactions. Indeed, the Kumada coupling of 2-iodo-5-methylthiophene (29) with ethynylmagnesium chloride gave the desired 2-ethynyl-5-methylthiophene (30) in only 35% yield, along with 24% of bis(5-methyl-2-thienyl)ethyne (31) [29], The high propensity for H-Mg exchange reaction to occur was blamed for the diarylethyne formation. 

In the presence of a ruthenium catalyst, 3-diazochroman-2,4-dione 716 undergoes insertion into the O-H bond of alcohols to yield 3-alkyloxy-4-hydroxycoumarins 717 (Equation 285) <2002TL3637>. In the presence of a rhodium catalyst, 3-diazochroman-2,4-dione 716 can undergo insertion into the C-H bond of arenes to yield 3-aryl-4-hydroxy-coumarins (Equation 286) <2005SL927>. In the presence of [Rh(OAc)2]2, 3-diazochroman-2,4-dione 716 can react with acyl or benzyl halides to afford to 3-halo-4-substituted coumarins (Equation 287) <2003T9333> and also with terminal alkynes to give a mixture of 477-furo[3,2-f]chromen-4-ones and 4/7-furo[2,3-3]chromen-4-ones (Equation 288) <2001S735>. 

Generally, the Sonogashira coupling reaction is achieved by a palladium-copper catalyzed reaction of aryl or vinyl halide and terminal alkyne [70-72], The presence of the copper co-catalyst is an obstacle, however, towards the metallodendritic approach of the system. In this context, only a few examples of copper-free procedures have been reported [73-77], involving for instance, in situ Pd(0) complex formation with bulky phosphines [78]. 

A more general method for arylation of terminal alkynes as well as electron-deficient alkynes is the Negishi Pd-catalyzed cross-coupling of aryl halides with alkynyl-zinc reagents. When using functionally substituted alkynylzincs, the deprotonation of 1-alkynes must be done with LDA instead of alkylithiums. 

Aryl triflates, like aryl halides, can undergo Pd-catalyzed coupling reactions with terminal alkynes (Scheme 14), and bromoallenes react with terminal alkynes - or acetylene under similar conditions to form allenynes (Schemes 15 and 16). 

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