3,5-Disubstituted aryl bromides

Disubstituted aryl bromides react with dialkylacetylenes, in the presence of catal)ttic quantities of both Pd(OAc)2 and PPhs, to give the corresponding aryl-substituted allenes in good yield (eq 111).20 ... 

Bromoquinoline (70), behaving similarly to a simple carbocyclic aryl bromide, was coupled with phenylethyne 121 to provide disubstituted ethyne 122 in 50% yield (2001JCS(P1)978). 

Even the sterically hindered 2,6-disubstituted aryl iodide 443 is carbonylated smoothly to give 445. Alkyl iodide present in the alcoholic component 444 remains intact under the carbonylation conditions. This carbonylation reaction is a key reaction in the synthesis of zearalenone (446) [216]. Optimal conditions for technical synthesis of the anthranilic acid derivative 448 from bromide 447 has been studied, and it has been found that A-acetyl protection of 447, which has a chelating effect, is important [217]. Cheaply available chlorides are rather inert [13]. The carbonylation of chloride 449 in the presence of DBU and Nal gives the amide 450 [218],... 

Hydroboration of acetylenic selenides with 9-BBN led to the regio- and stereoselective formation of a-selanylalkenyl boranes which were then converted into Z-a, -disubstituted vinyl selenides by cross-coupling reaction with aryl bromides [80] (Scheme 58). With unsubstituted acetylenic selenides, an inversion of regioselectivity during the hydrozirconation was observed [81,82]. 

Calo and coworkers have also studied the regioselectivity of Pd-nanoparticle catalyzed Heck arylations using aryl bromide and the 1,1-disubstituted olefins butyl methylacrylate and a-methylstyrene as the reactants in tetrabutylammonium bromide as the reaction medium and with tetrabutylammonium acetate as the base... 

HR of electron-rich aryl bromides with 1,1- or 1,2-disubstituted alkenes such as methyl methacrylate (71) and crotonate (72) proceeds at room temperature in dioxane with the same catalyst to provide 73 and 74 [26]. 

Typically, type 2 catalytic systems are exploited at high temperatures starting approximately at 120 °C, but usually exceeding 140 °C lower temperatures are sometimes possible after optimization. Thus, Giirtler and Buchwald [25] showed that, using their phosphine-free catalyst system, not only aryl iodides, but also aryl bromides 44, including electron-rich substrates, afford high yields in the arylation of disubstituted alkenes 45 at temperatures as low as 85-100 °C (44 46, Scheme 2.9). Both base and additive in this nice protocol are... 

Another example of the iron-catalyzed carbometallation reaction of unactivated alkynes was reported for the aryknagnesiation of alkyl(aryl)acetylenes [64b]. The addition of arylmagnesium bromide to the disubstituted aryl(alkyl)alkynes 234 was found to proceed efficiently in the presence of Fe(acac)j as a catalyst and a substoichiometric amount of an N-heterocyclic carbene (NHC) ligand (IPr) as an additive, which significantly increased the yield of this carbometallation process (Scheme 10.79). 

Scheme 22 Stille coupling of disubstituted thiophene with aryl bromides [115]...

The in situ preparation of aryl and heteroaryl azides from the corresponding aryl halides via L-proline-promoted Cnl-catalyzed coupling reactions in the presence of alkynes allows the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles (e.g. 226). Liang et al. also reported the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles (e.g. 227) from aryl bromides or iodides and terminal alkynes in the presence of sodium azide using diamine-promoted Cnl-catalyzed reactions. It has also been shown that this type of synthesis can be carried out in a mixture of the ionic liquid [bmim][BF4] and water (Scheme 3.32). Starting with boronic acids, the catalytic approach to aryl azides and l-aryl-1,2,3-triazoles can be carried out under milder reaction conditions and improved substrate tolerance (Scheme 3.33). In fact, it was demonstrated that both electron-rich and electron-poor aryl boronic acids 228 could be efficiently converted into the corresponding aryl azides (229) in the presence of sodium azide and CUSO4. A one-pot protocol... 

Addition of tributylstannyl-lithium to crotonaldehyde and protection of the resulting alcohol with chloromethyl methyl ether gives the stannane (192), which reacts with both alkyl and aryl aldehydes RCHO to form specifically the t/rr o-hydroxy-enol ethers (193). These latter compounds have been used to prepare tra/i5-4,5-disubstituted butyrolactones by hydrolysis and subsequent oxidation. Palladium-catalysed carbonylation of RX in the presence of organotin species constitutes a useful synthesis of unsymmetrical ketones, and in the example reported this year RX is an arenediazonium salt. The reaction, which is basically an aromatic acylation, proceeds in good to excellent yield. Another Pd-catalysed reaction of aromatics, this time aryl bromides, is their reaction with acetonyltributyltin (194), prepared from methoxytributyltin and isopropenyl acetate, to give the arylacetones (195). ... 

IV-Vinylimides readily undergo palladium-catalyzed vinylic substitution with aryl bromides to yield 2-styryl- and 2-phenylethylimines. With aryl iodides (eq 16), the reaction proceeds even in the absence of added phosphine, which opens the possibility of a sequential disubstitution of bromoiodoarenes. 

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