Reaction mechanism aryl iodide cross-coupling

The Ullmann reaction (Figure 13.4) represents another synthesis of substituted biphenyls. In this process an aryl iodide or—as in the present case—an aryl iodide/aryl chloride mixture is heated with Cu powder. It is presumed that under standard conditions the aryl iodide reacts in situ with Cu to form the aryl copper compound. Usually, the latter couples with the remaining aryl iodide and a symmetric biphenyl is formed. In a few instances it is also possible to generate asymmetric biaryls via a crossed Ullmann reaction. In these cases one employs a mixture of an aryl iodide and another aryl halide (not an iodide ) the other aryl halide must exhibit a higher propensity than the aryl iodide to couple to the arylcopper intermediate. It is presumed that the mechanism of the Ullmann reaction parallels the mechanism of the Cadiot-Chodkiewicz coupling, which we will discuss in Section 13.4. 

If the mechanism in Eq. (d) were the only path coordinatively saturated stable organometallics would not undergo transmetallation. However, certain coordinatively saturated ate complexes may also transmetallate e.g., the reaction of aryl iodides with alkynylaluminate complexes in the presence of Pd(PPh3)4 gives the corresponding cross-coupled products ... 

The cross-coupling reaction of alkenyl(fluoro)silanes with aryl halides sometimes produces, in addition to the desired ipso-cowpled products, small amounts of cmc-coupled products [14]. The czne-coupling is often striking in the reaction with organotin compounds. The isomer ratio of products produced by the reaction of l-fluoro(dimethyl)silyl-l-phenylethene with aryl iodides is found to depend on the electronic nature of a substituent on aryl iodides (Eq. 11) an electron-withdrawing group like trifluoromethyl and acetyl favors the formation of the ipso-coupled product. To explain the substituent effect, the mechanism depicted in Scheme 3 is proposed for the transmetalation of alkenylsilanes with palladium(ll) complexes. It is considered that an electron-donating substituent on Ar enhances... 

In 2009, Liu and coworkers [40] reported the decarboxylative cross-coupling of potassium polyflourobenzoates with aryl iodides mediated by a copper-only system (both the decarboxylation and the cross-coupling steps are cattilyzed solely by copper). The reaction is very practical for the synthesis of polyfluorobiaryls from readily available and nonvolatile polyflourobenzoate salts (Scheme 3.23). On the basis of DFT ctilculations, the authors proposed a mechanism in which the initially formed copper(I) carboxylates extrude COj with formation of polyfluorophenylcopper(I) species (Scheme 3.23), which then react with aryl h llides in an oxidative addition/reductive elimination sequence, yielding the unsymmetrical biaryl products [40]. 

Copper(I) complexed with 1,10-phenanthroline has been used in the arylation of imidazo[l,2-a]pyridines by aryl bromides, iodides, and triflates to give products, (139), substituted at the 3-position. The mechanism is likely to involve initial deprotonation at the 3-position followed by cupration and oxidative addition of the aryl halide. The copper-mediated cross-coupling of indoles with 1,3-azoles is assisted by chelation of a, readily removed, 2-pyrimidyl group and leads to products such as (140). In this reaction, two carbon-hydrogen substitutions are required and it is likely that initial cupration of the 1,3-azole is followed by chelation-assisted formation of a bis(heteroaryl) copper species before oxygen-promoted reductive elimination... 

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