Suzuki reaction triflates

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). 

The Suzuki reaction has proved extremely versatile and has found extensive use in natural product. synthesis. " Arylboronic acids [ArB(OH)2 are the usual substrates in this reaction together with arylhalides or triflates (Ar X, X = halogen... 

There are also several examples of the use of Suzuki reactions in scale-up synthesis of drug candidates. In the synthesis of CI-1034, an endothelin antagonist, a triflate,... 

In conclusion, the already rich chemistry of pyrroles is greatly expanded by the palladium reactions presented in this chapter. The abundance of both 2- and 3-pyrrolyl halides and triflates has led to many examples of high-yielding Negishi, Suzuki, Stille, Sonogashira, and Heck reactions. Noteworthy are the excellent approaches to alkynyl pyrroles and porphyrins using Sonogashira, Stille, and Suzuki reactions. 

Sn2 substitution using organocopper reagents is an efficient method for the synthesis of 3-substituted olefins. In the synthesis of farnesyl diphosphate analogues (43, 45) as potential inhibitors of the enzyme protein-farnesyl transferase, for example, organocopper methodology was compared with the Stifle reaction [33] and the Suzuki reaction [34], frequently used in the coupling of vinyl triflates with... 

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... 

Different conditions (including additives and solvent) for the reaction have been reported,often focusing on the palladium catalyst itself," or the ligand." Catalysts have been developed for deactivated aryl chlorides," and nickel catalysts have been used." Modifications to the basic procedure include tethering the aryl triflate or the boronic acid to a polymer, allowing a polymer-supported Suzuki reaction. Polymer-bound palladium complexes have also been used." " The reaction has been done neat on alumina," and on alumina with microwave irradiation." Suzuki coupling has also been done in ionic liquids," in supercritical... 

Similarly, during a study of synthetic routes to several 3,4-diarylpyrrole marine alkaloids, it was found that bis-triflate 128 can be induced to undergo mono-, bis-, or sequential bis-Suzuki reactions with methoxyphenylboronic acids [44],... 

Nishida employed boronic acid 106 and the corresponding TV-TBS boronic acid in Suzuki reactions with a series of heteroaromatic halides [118], The TV-TIPS group proved superior to TV-TBS. 3-Indoleboronic acid 96 was employed by Neel to prepare bis(indolyl)maleimides such as 109 [119]. However, since the standard Suzuki conditions failed (triflate 108 apparently decomposing under the reaction conditions), the use of a phosphine-free Pd catalyst [120] and cesium fluoride [121] was necessary and gave 109 in an acceptable yield of 55%. 

General procedure for the Suzuki reaction using triflates [121] The following procedure employs K2CO3, which may cause hydrolysis of labile esters within the coupling components. 

Halopyridines or pyridinyl triflates take part in palladium-catalysed reactions -Heck, carbonylation, and coupling reactions, for example with alkynes, or in Suzuki reactions with arylboronic acids,and cyclopropylboronic acids. 

Application of immobilized palladium catalyst under the action of MW, with phase-transfer agents, has also been reported to promote the Suzuki reactions of a range of aryl halides and triflates in solvents such as water and ethanol under MW conditions [120, 121]. Similar results were obtained when aryl halides were attached to a PEG matrix as para-substituted benzoates [122]. It was found that conventional thermal conditions induced up to 45% cleavage of the benzoates whereas this side reaction was suppressed when MW conditions were employed. 

These palladium-catalysed reactions involve insertion of the palladium into the carbon-bromine or carbon-triflate bond, reaction with the organometallic species (alkenyl stannane in a Stille reaction, arylboronic acid in a Suzuki reaction, or alkynyl copper species in a Sonogashira reaction) and reductive elimination to give the products shown below. 

Aldous and co-workers also reported extensive results on palladium-catalyzed coupling reactions. They introduced the utility of electron-deficient pyridazinyl triflate 136 in Stille and Suzuki biaryl cross-couplings with electron rich aryl stannanes and aryl boronales 137 <01SL150>. Electron deficient aryl stannanes resulted in more sluggish reactions and poor yields. In general, Suzuki reactions were found to be better than the corresponding Stille couplings. 

Under noncompetitive conditions, Greaney functionalized C2-chlorides or C4-triflates with a variety of aryl and heteroaryl boronic acids. The authors attempted Suzuki reactions with the C2-sulfonates but found facile thermal decomposition with both triflates and nonaflates. ... 

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