Suzuki reaction results

So far we have considered olefins and alkynes as terminating agents. Another reaction, however, was available to effect C-C coupling in the last step, the Suzuki reaction. Results were satisfactory under the conditions shown in the Table (28). 

Bromoquinolines behave in the Suzuki reaction similarly to simple carbocyclic aryl bromides and the reaction is straightforward. Examples include 3-(3-pyridyl)quinoline (72) from 3-bromoquinoline (70) and 3-pyridylboronic acid (71) (91JOC6787) and 3-phenyl-quinoline 75 from substituted 3,7-dibromoquinoline 73 and (2-pivaloylaminophenyl)boronic acid 74 (95SC4011). Notice that the combination of potassium carbonate and ethanol resulted in debromination at the C(7) position (but the... 

Many types of functional groups are tolerated in a Suzuki reaction, and the yields are often good to very good. The presence of a base, e.g. sodium hydroxide or sodium/potassium carbonate, is essential for this reaction. The base is likely to be involved in more than one step of the catalytic cycle, at least in the transmetal-lation step. Proper choice of the base is important in order to obtain good results." In contrast to the Heck reaction and the Stille reaction, the Suzuki reaction does not work under neutral conditions. 

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

AT-acetyltryptamines could be obtained via microwave-assisted transition-metal-catalyzed reactions on resin bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide. While acceptable reaction conditions for the application of microwave irradiation have been identified for Stille heteroaryla-tion reactions, the related Suzuki protocol on the same substrate gave poor results, since at a constant power of 60 W, no full conversion (50-60%) of resin-bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide could be obtained even when two consecutive cross-coupling reaction cycles (involving complete removal of reagents and by-products by washing off the resin) were used (Scheme 36). Also under conventional heating at 110 °C, and otherwise identical conditions, the Suzuki reactions proved to be difficult since two cross-coupling reaction cycles of 24 h had to be used to achieve full conversion. 

Alternatively, 3-phenyl pyrazinone was prepared via Suzuki reaction, when a polymer-bound pyrazinone was irradiated with 4 equiv of phenylboronic acid, 5 equiv of Na2C03 and 20 mol % of Pd[P(Ph)3]4 as the catalyst in DMF as the solvent (Scheme 36). Contrary to the results obtained in solution phase [29], all attempts to drive the reaction toward the formation of disub-stituted compound, using higher equivalents of reagents or longer reaction times, were unsuccessful. Apphcation of aqueous conditions afforded mixtures of 3-mono and 3,5-disubstituted pyrazinones. 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

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. 

Pd(dppf)Cl2] was used as the catalyst. A particularly noteworthy aspect of this publication is the introduction of a one-pot borylation/Suzuki reaction of 5-bromo-terthiophene with commercially available bis(pinacolato)diboron. The resulting sex-ithiophene was obtained within 10 min of microwave irradiation in 84% isolated yield. The same concept was also applied for the synthesis of modified oligothio-... 

Pyridine-containing tricyclic compounds have been produced via a sequence consisting of a Suzuki reaction and a subsequent annulation. Gronowitz et al. coupled 2-formylthienyl-3-boronic acid with 3-amino-4-iodopyridine. The resulting adduct spontaneously condensed to yield thieno[2,3-c]-l,7-naphthyridine 59 [47]. They also synthesized thieno[3,4-c]-l,5-naphthyridine-9-oxide (60) in a similar fashion [48]. Neither the amino nor the N-oxide functional group was detrimental to the Suzuki reactions. 

While a hydroxymethyl group has been succesfully used to temporarily block the lactam nitrogen of halopyridazin-3(2//)-ones such as 191 for Suzuki reactions <2003TL4459>, and the resulting aryl-2-hydroxymethylpyridazin-3(2//)-ones have been immediately deprotected in situ via a base-induced or thermal retro-ene reaction (Equation 39), two recent reports show that Suzuki reaction on unprotected substrates like 5-chloropyridazin-3(2//)-one 192 is feasible (Scheme 47) <2005JME6004, 2006JME2600>. 

Chloro-P-carboline (25) has served as a common intermediate in palladium-catalyzed cross-coupling reactions, offering easy access to several pyridine alkaloids. In Bracher s total synthesis of perlolyrine (27), a P-carboline alkaloid, the Suzuki reaction of 25 with 5-formylfuranyl-2-boronic acid (26) formed the C-C bond between the pyridine and the furan rings <92LA1315>. Reduction of the resulting Suzuki adduct with NaBIL subsequently... 

Boronic acids can be reversibly esterified with resin-bound diols (Figure 3.15). The resulting boronic esters are stable under the standard conditions of amide bond formation, but can be cleaved by treatment with water under acidic or neutral conditions to yield boronic acids. Treatment of the resin-bound boronic esters with alcohols yields the corresponding boronic esters [197]. Resin-bound boronic esters are suitable intermediates for the Suzuki reaction [198], Treatment with H202 leads to the formation of alcohols (Entry 8, Table 3.36), while treatment of resin-bound aryl boronates with silver ammonium nitrate leads to the conversion of the C-B bond into a C-H bond (Entry 14, Table 3.46). 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

Suzuki reaction A palladium catalyzed reaction that results in the formation of new carbon to carbon bonds by reacting an organohalide or organotriflate with an organoboronic acid. 

The different synthetic transformations investigated with this system included nucleophilic aromatic substitutions, esterifications and Suzuki reactions and are shown in Scheme 18. In all cases, product yields were similar to those using conventional heating and were easily scalable to multigram quantities [67]. Within 5 h more than 9 g of the resulting phenethylamine could... 

Salen-like ligands have also been used to complex, and hence immobilize, a number of metals onto polystyrene and silica for use in a variety of cross-coupling reactions. The salen-palladium complex 32 was used in Suzuki reactions (Figure 4.7). The column containing the immobilized catalyst was heated to 1000 C in a water bath and the reagents were recirculated continuously at a flow rate of 6 pi/min for 5 h, resulting in conversions in the range of 65-75% [154],... 

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