Arylboronic acids, electron-poor

This reaction can be carried out with secondary amines, sterically hindered primary amines, hydrazines or anilines in dichloromethane at room temperature. The range of potential nucleophilic partners includes alkenylboronic acids, and electroneutral as well as electron-rich (hetero-)arylboronic acids. The conversion of electron-poor boronic acids can be effected at elevated temperatures (MW) in suitable solvents. 

The Pd-catalysed three-component coupling of readily available aryl iodides (53), internal alkynes (54), and arylboronic acids (55) has been developed as a one-step, regio- and stereo-selective route to tetrasubstituted alkenes (56) in good to excellent yields, although electron-poor aryl iodides and dialkylalkynes normally afford only low yields under standard reaction conditions. The right combination of substrates and reaction conditions has been shown to be important for attaining high yields. The presence of water substantially increased the yields of the desired tetrasubstituted... 

One of the challenges in the Suzuki-type cross-coupling is to extend this reaction from electron-rich aryl iodides, bromides, and triflates to less reactive aryl sulfonates and aryl chlorides, which show poor reactivity in terms of oxidative addition in the catalytic cycle. Aryl mesylates, benzenesulfonates, and tosylates are much less expensive than triflates, and are unreactive toward palladium catalysts. The Ni(0)-catalyzed Suzuki-type cross-coupling reaction of aryl sulfonates, including mesylates, with arylboronic acids in the presence of K3P04 has been reported [123]. 

Upon investigating the literature, Lauren noted that arylboronic acids substituted with electron-withdrawing groups often experience extensive protodeboronation and poor yields under the standard Suzuki conditions that utilize aqueous NaaCOs as a base. A solution to this problem lies in either the use of a milder base or nonaqueous conditions. Therefore, Lauren chose to employ NaHCOj as a base. The arylboronic acid derivative of 6-bromopiperonal was coupled with the suitably elaborated aryl iodide to provide the desired biaryl ( )-3 in moderate yields (Eq. 15). 

Scheme 4.26 shows the development of two general reactions based on copper(I) thiophene-2-carboxylate (CuTC) or Cu(OAc)2 for the formal arylation of imtnes with arylboronic acids [62]. The O-acetyl or O-pentafluorophenyl oximes react with a wide range of electron-rich, electron-poor and electron-neutral boronic acids, and even ortho-substituted substrates react well. The mechanism is proposed to proceed, as shown in Scheme 4.27, via an initial oxidative addition of the copper(I) species, either CuTC or through reduction of Cu(OAc)2 by the boronic acid, to the ketoxime O-carboxylate. This is followed by transmetallation and reductive elimination to generate the final product and regenerate the catalytically active copper(I) species. 

The use of a-imino esters with bulky arylboronic acids (with ortho substituents or a naphthyl group) also proceeded successfully to afford the corresponding a-amino esters with high enantiose-lectivity. Both electron-rich and electron-poor arylboronic acid derivatives can be used. The utility of this reaction was demonstrated by the same group, in the concise asymmetric synthesis of the 1-naphthyl-a-amino acid and the corresponding amino alcohol, in just one step without any racem-ization occurring (Scheme 6.30) [38]. 

The two key catalytic intermediates have been observed by electrospray mass spectrometry [394]. Although the exact role and influence of the base remains unclear [395], the transmetallation is thought to be facilitated by base-mediated formation of the tetracoordinate boronate anion [396], which is more electrophilic than the free boronic acid (Sections 1.5.1 and 1.5.2). A useful carbonylative variant has also been developed to access benzophenones (Equation 70) [397], which can also be produced from the coupling of acid chlorides [398] or anhydrides [399], A variant of this method allows the preparation of a, 3-unsaturated esters from alkenylboronic esters [243]. In all of these reactions, one dreaded limitation with some ortho-substituted and electron-poor arylboronic acids is the possible occurrence of a competitive protolytic de-boronation, which is exacerbated by the basic conditions and the use of a transition metal catalyst (Section 1.5.1). Methods to minimize this side reaction were developed in particular the use of milder alternative bases [400] such as fluoride salts [401], and... 

---