Suzuki drawback

The Suzuki-Miyaura and Heck reactions were recently also reported under conventional heating conditions [39,40]. A variety of 3-chloro pyrazinones were reacted with commercially available (hetero)aryl boronic acids or the alkyl-9-BBN derivatives under either classical or slightly modified Suzuki conditions to generate the 3-substituted analogues, however having the drawback of longer reaction times of up to 12 h of reflux. 

A drawback of the Heck-type reaction is that it is not strictly regioselective [119]. Depending on the substituents >1% of 1,1-diarylation is observed. Soluble 2,5-dialkoxy-PPVs 63 or 2-phenyl-PPV PPPV 93, without 1,1-diarylated moieties, were synthesized by Heitz et al. in a Suzuki-type cross coupling of substituted 1,4-phenylenediboronic acids and fran5-l,2-dibromoethylene, catalyzed by Pd(0) compounds [120]. However, about 3% of biaryl defect structures are observed in the coupling products (M up to 12,000), resulting from homocoupling of boronic acid functions. 

As an example, consider the use of PVPy as a solid poison in the study of poly(noibomene)-supported Pd-NHC complexes in Suzuki reactions of aryl chlorides and phenylboroiuc acid in DMF (23). This polymeric piecatalyst is soluble under some of the reaction conditions employed and thus it presents a different situation from the work using porous, insoluble oxide catalysts (12-13). Like past studies, addition of PVPy resulted in a reduction in reaction yield. However, the reaction solution was observed to become noticeably more viscous, and the cause of the reduced yield - catalyst poisoning vs. transport limitations on reaction kinetics - was not immediately obvious. The authors thus added a non-functionalized poly(styrene), which should only affect the reaction via non-specific physical means (e.g., increase in solution viscosity, etc.), and also observed a decrease in reaction yield. They thus demonstrated a drawback in the use of the potentially swellable PVPy with soluble (23) or swellable (20) catalysts in certain solvents. 

Other Pd cross-coupling reactions such as Heck [52] and Suzuki [53] reactions have also been used for macrocyclizations. The main drawback for Pd catalyzed macrocylization is the yield, that is often somewhat disappointing if compared with other established methods. Also, the introduction of the required coupling components (e.g., trialkyltin group, vinylic iodide) can be difficult in some compounds. In other cases, Pd-catalyzed side reactions such as double bond migration or allylic activation can occur. 

The Stille Coupling is a versatile C-C bond forming reaction between stannanes and halides or pseudohalides, with very few limitations on the R-groups. Well-elaborated methods allow the preparation of differen, products from all of the combinations of halides and stannanes depicted below. The main drawback is the toxicity of the tin compounds used, and their low polarity, which makes them poorly soluble in water. Stannanes are stable, but boronic acids and their derivatives undergo much the same chemistry in what is known as the Suzuki Coupling. Improvements in the Suzuki Coupling may soon lead to the same versatility without the drawbacks of using tin compounds. 

The moisture stability of the organostannanes and good functional group tolerance of the reaction make it most extensively used in coupling reactions. However, toxicity and low polarity of tin compounds are certain drawbacks of the use of the Stille reaction. The Suzuki coupling makes use of boronic acids and their derivatives, which is an improvement on the Stille coupling. In contrast to the Suzuki, Kumada, Heck and Sonogashira reactions which are carried out under basic conditions, the Stille reaction can be carried out under neutral conditions. 

One drawback of the Stille coupling is that the tin by-products are toxic and are not easily removed from the product. A solution to this problem developed by Suzuki uses a boronic acid in place of the organ-otin compound. The boron-containing by-products are innocuous and are easily removed because of their solubility in water. The Suzuki coupling has found widespread use in organic synthesis (Scheme 10.20). These reactions are extremely important and the methodology is extensively used, particularly in the search for new pharmaceutical products. 

Both Heck and Suzuki reactions proved the worth of hydrophobic immobilization, and in the latter case the higher reaction rate was an additional advantage. Beneficial, too, is the fact that conventional catalysts could be used without further modification, because there was no need to adjust the ligand solubility. A major drawback of this procedure, however, is the restriction in the choice of suitable reactants. 

A drawback of the aqueous protocol in the Suzuki reaction is the possibility of protonolysis, which sometimes happens with sterically hindered boronic acids, in which case the rate of cross-coupling reaction may become lower than the rate of side reactions. Thus, in the reaction of methyl 5-bromonicotinate with sterically hindered o-tolylboronic acid, the use of a biphasic technique with Na2C03 as a base gave poor results in comparison with the reaction in anhydrous DMF in the presence of EtsN (Scheme 37). " ... 

Carbonylative Suzuki Cross-Coupling Reactions Carbonyladve Snzuki cross-coupling is a useful SCR (boronic acid + aryl halide + CO) to prepare asymmetric substimted kehmes [70]. One of the main drawbacks of this methodology is the direct couphng reaction, which forms biaryl products without carbon monoxide insertion, particularly with electron-deficient aryl haUdes. 

Some drawbacks of the precursor routes mentioned above have been overcome by the use of polycondensation- and C-C-bond-coupling reactions. To produce soluble PPV-, poly(thiophene)-, or poly(pyrrol) derivatives for spin coating preparation, various types of transition metal catalyzed reactions, such as the Heck-, Suzuki-, and Sonogashira-reaction, Wittig- and Wittig-Horner-type coupling reactions, or the McMurry- and Knoevenagel-condensation have been utilized. 

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