Aryl boronic acid, Suzuki-Miyaura

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. 

An efficient aqueous phase Suzuki-Miyaura reaction of activated aryl chlorides with aryl boronic acids has been reported. The method uses a new D-glucosamine-based dicyclohexylarylphosphine ligand for the palladium catalyst and works well with nitro-and cyano-activated chlorides.32 The aryl fluoride bond has been considered inert to palladium-catalysed substitution reactions. However, a computational study, backed up by experiment, shows that the presence of a carboxylate group ortho to fluorine will allow reaction both with phenylboronic acids in a Suzuki-type reaction and with organotin reagents in a Stille-type reaction the presence of the adjacent oxyanion stabilizes the transition state.33... 

An interesting polymer-assisted variant of the Suzuki-reaction was recently disclosed by Vaultier and coworkers (Scheme 17) [43]. Aryl boronic acids can be immobilized on an ion exchange resin. Under Suzuki-Miyaura coupling conditions bisaryl species are released into solution and isolated with minimum purification. The authors also demonstrated that this strategy can be employed for the synthesis of macroheterocycles. 

When IBioxl2 HOTf was employed as the ligand precursor for the Suzuki-Miyaura coupling of sterically hindered aryl chlorides and aryl boronic acids, excellent to good yields were obtained in refluxing toluene for a variety of starting materials (Table 6). Notably, this work represents the first report of tetra-orf/zo-substitulcd biaryl compounds achieved from aryl chlorides [143]. 

The catalytic activity of benzothiazole-oxime-based Pd (Il)-complexes (xxxv) was evaluated in Suzuki-Miyaura and Heck-Mizoroki C-C cross coupling reactions of aryl bromides and chlorides with aryl boronic acid and olefins under microwave conditions in water was studied by Dawood [55]. 

SCHEME 25.5(A) Microwave-assisted Suzuki-Miyaura coupling of bromofuranone with aryl boronic acid (Reference 53). 

Most of the mechanistic work on this reaction has been devoted to determining the role of the base. Its most obvious function would be to complex the Lewis-acidic boron reagent, rendering it nucleophilic and thus activating it toward transmetallation. However, Miyaura, Suzuki, and coworkers noted that an electron-rich tetracoordinate boronate complex was less reactive than a trivalent boronic ester.From this, they surmised that the role of the base was not to activate the boron toward transmetallation, but rather to transform the palladium halide intermediate to the hydroxide or alkoxide species, which would then be more reactive toward boron. However, in a mass spectrometry study of a reaction between a pyridyl halide substrate and an aryl boronic acid, Aliprantis and Canary saw no evidence of palladium hydroxide or alkoxide intermediates, despite observing signals in the mass spectra assignable to every other palladium intermediate of the proposed catalytic cycle. 

The allylic carbamate 193 formed as shown in Scheme 17 can be exploited in the synthesis of a pancratistatin analogue. Thus, Suzuki-Miyaura cross-coupling of this carbamate with aryl boronic acid 61 (Scheme 18) afforded the expected arylated cyclohexene 200 (87%) that upon sequential treatment with diborane, alkaline hydrogen peroxide, aqueous acid then acetic anhydride gave the triacetate 201 (42%). Subjecting this last compound to the Bischler-Napieralski reaction... 

A simple modification of the reaction sequence shown above has allowed for the synthesis of e f-narciclasine (cnt-188). Thus, as shown in Scheme 20, Suzuki-Miyaura cross-coupling of the previously prepared 2-bromocyclohex-2-enamine 209 with the readily synthesised aryl boronic acid 212 afforded the expected lactam 213 (63%). Once again, treatment of the last compound with TMS-Br resulted in exhaustive cleavage of the MOM ether residues and, this time, the formation of the target compound cnt-188 (48%). 

Romagnoli et al. have reported a convergent synthesis of a class of microtubule targeting agents where they aj lied the Suzuki-Miyaura reaction to highly substituted 5-bromothiazoles. With various aryl boronic acid, highly substituted thiazole derivatives were prepared and evaluated for their anti-proliferative activity against a panel of human tumor cell lines. 

In the strategy described in Fig. 16b, the linear precursor is not built on the polymer, but the final cyclization reaction using the Suzuki-Miyaura coupling takes place on a polymer. The aryl boronic acid is captured on a Dowex ammonium hydroxide resin, leading to the polymer ionically bonded borate, which is subsequently treated in the appropriate conditions to give the final macrocyle. This methodology is called resin capture-release.. ... 

Iron-catalysed direct Suzuki-Miyaura cross-coupling between Af-het-erocyclic amines and aryl boronic acids. 

For 2-nitrobiphenyls 5, an efficient and flexible synthesis by Suzuki-Miyaura coupling of 2-nitrodiazonium salts 4 with aryl boronic acids is available [200]. 

Treatment of a benzyl-substituted and symmetrical bis-enol tri-flate with various aryl boronic acids in the presence of Pd(OAc)2 results in a Suzuki-Miyaura cross-coupling reaction, then an intramolecular Heck reaction between the remaining triflate residue and the benzyl group and so as to give the illustrated product (eq 96).i i... 

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