Miyaura boration

The first step of the Miyaura boration is the oxidative addition of the Pd ° -complex into the C-X bond of the aryl halide. Next, a transmetallation takes place, the exact mechanism of which depends on the nature of the substrate, and finally the reductive elimination affords the product. 

The total synthesis of the proteasome inhibitor cyclic peptide TMC-95A was accomplished by. S.J. Danishefsky and co-workers. The biaryl linkage in the natural product was constructed by a Suzuki cross-coupling between an aryl iodide and an arylboronic ester derived from L-tyrosine. The required arylboronic pinacolate substrate was prepared using the Miyaura boration. The aryl iodide was exposed to b/s(pinacolato)diboron in the presence of a palladium catalyst and potassium acetate in DMSO. The coupling proceeded in high yield and no symmetrical biaryl by-product was observed. 

A novel macrocyclization reaction was developed based on a domino Miyaura boration intramolecular Suzuki crosscoupling sequence in the laboratory of J. Zhu. " This strategy was applied in the synthesis of biaryl-containing macrocycles. The diiodide substrate was dissolved in degassed DMSO, and then the catalyst and the base were added. Successful macrocyclization required extensive experimentation, and the authors determined that the concentration and the nature of the base were the two most important factors. Interestingly, potassium carbonate is not suitable as a base in the Miyaura boration, since it tends to give biaryl by-products, but in this particular macrocyclization reaction it proved to be completely ineffective because the reaction failed to take place. 

The first total synthesis of the potent antibiotic marine natural product ( )-spiroxin C was completed by T. Imanishi et al., who employed a TBAF-activated Suzuki cross-coupling as the key step to form the biaryl linkage. The coupling partner naphthylborate ester was prepared using the Miyaura boration. 

The efficient synthesis of a potent topoisomerase I poison terbenzimidazole was developed in the laboratory of P.J. Smith. The desired aryl-aryl bonds were created via iterative Suzuki-cross couplings. The arylboronic ester was derived from 1-benzyl-5-iodo-1/-/-benzimidazole using the Miyaura boration. 

Pd-catalyzed Miyaura boration Pd-catalyzed cross-coupling of aromatic and heteroaromatic halides or triflates with tetraalkoxydiboron compounds to give arylboronic and heteroarylboronic esters. 296... 

The cA-bis(boryl)alkenes 482 are obtained by bis-boration of terminal alkynes catalysed by a Pt complex [185]. Pd and Rh complexes are inactive. Then the (Z)-1,2-diphenylalkene 483 is prepared by Pd-catalysed Suzuki-Miyaura coupling of 482 with iodobenzene. 

Iron-catalyzed Suzuki-Miyaura coupling reactions were also reported by Nakamura and colleagues (entry 27) [67]. Alkyl halides 1 and mixed pinacol aryl(butyl)borates, generated in situ from arylboronates and butyllithium, were used as the reagents and 10 mol% of the iron complexes 16a or 16b as the catalysts. The addition of 20 mol% of MgBr2 was essential for the success of the reaction. Products 3 were isolated in 65-99% yield. The methodology tolerates ester and nitrile functions. The reaction starts probably by initial boron-iron transmetalation to generate a diaryliron(II) complex. 

The palladium-catalyzed coupling of boronic acids (as well as other boron derivatives) with aryl and vinyl halides and psendohalides is known as the Suzuki or Suzuki-Miyaura reaction. Because boron is nontoxic, this reaction has been used in pharmaceutical syntheses. In addition, hydroboration or borate substitution allows for the synthesis of virtually any desired coupling partner. For these reasons, as well as the high yields and functional group compatibility, the Suzuki reaction is the first reaction to consider for carrying out a cross coupling. Representative substrates and catalysts are shown in Scheme 17. The various bases are used to generate four-coordinate boron ate complexes that are more reactive in transmetalation. 

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.. ... 

Although the SM reactions of haloferrocenes proceed rather slow, they are clean and chemoselective, providing the production of arylferrocenes which would be hardly accessible by other strategies. Several papers regarding improved and alternative technics for performing the Suzuki-Miyaura reactions have been published. A useful procedure involves transmetallation of (half amount) simple aryl halides with only 0.5 eq. of -BuLi, followed by quenching the resulted aryllithium reagent with trimethyl borate [88], Thus obtained arylboronic ester is coupled under the standard SM conditions method A) with an excess of parent aryl halide to furnish the symmetrical biaryl in fair yields. For example, 2-bromoanisole (218) was coupled by this way to afford 2,2 -dimethoxybiphenyl (92) in 56% yield [88], Scheme 36. 

The Suzuki-Miyaura coupling joins an alkenyl or aryl borate with an alkenyl or aryl halide in the presence of a palladium catalyst. The stereochemistry of alkenyl reactants is preserved in the coupling. 

During studies on rhodium-catalyzed Suzuki-Miyaura cross-coupling reactions, Miura and coworkers reported more recently on the use of less-toxic tetraphenyl-borate 6 for the direct arylation of imines (Scheme 9.4) [16]. Unfortunately, rather low yields of mono- and di-arylated products were obtained, this being due to a reduction of the starting material via a sequence consisting of a rhodium hydride addition and subsequent protonation. The reduction of the imine is mandatory for the regeneration of a rhodium chloride species, and thereby for catalytic turnover. 

Other activated and stable borates were developed over the past few years for use in the Suzuki-Miyaura cross-coupling reaction. Whitehead and coworkers [88] have developed activated sodium trihydroxyborate salts through the treatment of boronic... 

Scheme 9.40 Ethynyl(trialkoxy)borates as efficient alkynylation reagents in Suzuki-Miyaura...

Mechanistic knowledge of the Suzuki-Miyaura reaction is far from complete [22d, 23], Although a base is obligatory and phenylboronic acids are known to form borates at high pH, evidence is not available for an RB(OH)3 intermediate. Especially intriguing, compared with other cross-coupling processes, is the unknown step. 

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