Reaction Suzuki reaction

Suzuki reaction Reaction of an organic halide with an organoboron reagent in the presence of a palladium catalyst (Section 26.2)... 

The applications of microwave chemistry to organic chemistry are too numerous to mention. A few representative examples will be given to illustrate the scope and utility. Microwave chemistry is widely used in synthesis. Examples include the Heck reaction (reaction 13-10)," the Suzuki reaction (reaction 13-12)," the Sonogashira reaction (reaction 13-13)," Ullman type couplings (reaction... 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

To date a number of reactions have been carried out in ionic liquids [for examples, see Dell Anna et al. J Chem Soc, Chem Commun 434 2002 Nara, Harjani and Salunkhe Tetrahedron Lett 43 1127 2002 Semeril et al. J Chem Soc Chem Commun 146 2002 Buijsman, van Vuuren and Sterrenburg Org Lett 3 3785 2007]. These include Diels-Alder reactions, transition-metal mediated catalysis, e.g. Heck and Suzuki coupling reactions, and olefin metathesis reactions. An example of ionic liquid acceleration of reactions carried out on solid phase is given by Revell and Ganesan [Org Lett 4 3071 2002]. 

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... 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

The mechanism " of the Suzuki reaction is closely related to that of the Stille coupling reaction, and is also best described by a catalytic cycle ... 

Of particular synthetic importance is the coupling of aryl- and hetarylboronic acids to aryl- and hetaryl halides (or triflates), allowing for a convenient synthesis of biphenyls, even sterically demanding derivatives such as 14, hetaryl phenyls and Zj/ -hetaryls. With appropriately disubstituted aromatic substrates, the Suzuki coupling reaction can be applied in the synthesis of polyphenylene materials. 

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. 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-aryhndoles fEq. 10.50. 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole " and 5-amino-7-ethoxycarbonyhndole for use in synthesis of l//-pyrrolo[3,2-g quina2ohne ring system fEq. 10.51 " have been prepared from the appropriate o-nitrotoluene. 

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

Figure 5.21 (a) Monomers and (b) polymers syntheses by Suzuki reaction. 

The Suzuki reaction was also used to prepare the polyketone since this particular reaction tolerates the subsequent step (Scheme 6.19).135 Palladium-catalyzed cross-coupling of aromatic diacid chlorides and bis(trimethylstannane) monomers was utilized to prepare poly(arylene ether ketone)s.136... 

Bromo-6,7-dichloro-2-quinoxalinamine (60, R = Br) gave 6,7-dichloro-3-phenyl-2-quinoxalinamine (60, R = Ph) by the Suzuki reaction [PhB(OH)a,... 

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... 

The first microwave-assisted Suzuki reactions involving heteroaromatic skeletons were reported in 1996 [35]. Hallberg et al. Hnked the substrates 4-iodo and 4-bromobenzoic acid to a TentaGel-Rink resin (Scheme 16). Suzuki reactions on these soUd-phase-Unked substrates were easily performed in less than 4 min using a constant microwave irradiation power (45 W) (no temperature control Standard acidic cleavage with TEA yielded the corresponding biaryls with an excellent yield. 

Other types of HIV-1 protease inhibitors have also been prepared using microwave-promoted Suzuki reaction [37]. The symmetric cyclic sulfamide (3K,4S,5S,6it)-3,6-bis(phenoxymethyl)-2,7-bis[4-(2-thienyl)benzyl]-l,2,7-thi-adiazepane-4,5-diol 1,1-dioxide, for instance, was synthesized via cross-couphng of (3aS,4R,8it,8aS) - 5,7 - bis(4 - bromobenzyl) - 2,2 - dimethyl - 4,8 - bis-(phenoxymethyl) hexahydro [1,3] dioxolo [4,5 - d] [ 1,2,7 ] - thiadiazepine 6,6 - dioxide with 2-thienylboronic acid for 3 min at 45 W (Scheme 19). 

Solvent-free microwave-assisted Suzuki reaction on AI2O3 as soHd support using KF as base has also been described in the hterature by Villemin [38] (Scheme 20). Ligand-free Pd(OAc)2 was used as a precatalyst. In a reaction... 

Heteroarylphenylalanines could be smoothly obtained via microwave-promoted Suzuki reaction of heteroaryl halides with 2-amino-3-[4-(dihy-droxyboryl)phenyl]propanoic acid (Scheme 28) [46]. Interestingly, the free amino acid could be used without any protection of the amine and carboxylic acid fimctionahty. When 4-(dihydroxyboryl)-L-phenylalanine was used as organometallic partner no racemization was observed. The carboxylate anion and free amino group seem to shield the a-C - H from deprotonation and thus hmit racemization. 

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