Miyaura borylation reaction

The Miyaura borylation reaction enables the synthesis of boronates by cross-coupling of bis(pinacolato)diboron (B2pin2) with aryl halides and vinyl halides. 

Fig. 5.17 The Miyaura borylation reaction. (From http-JAMWW.organic-chemistry.org/namedreactions/...

Fig. 5.18 The catalytic cycle of the Miyaura borylation reaction. (From httpj/www.organic-chemistry. org/namedreactions/miyaur3.GIF).

Palladium-catalyzed reaction of aryl halides with diboron reagent to produce aryl-boronates. Also known as Hosomi-Miyaura borylation. 

Crucial for the success of the borylation reaction is the choice of an appropriate base, as strong activation of the product enables the competing Suzuki Coupling. The use of KOAc and KOPh is actually the result of a screening of different reaction conditions by the Miyaura group. 

Although not a palladium-catalyzed reaction, the Ir(I)-catalyzed C-H borylation reaction developed independently by Smith and Malezcka [58] and Hartwig and Miyaura [59] deserves some mention in the context of indole and pyrrole functionalization. Based on the original studies, indoles and pyrroles can be borylated (and hence cross coupled under Suzuki conditions) to form either the C2 or C3 functionalised products (Scheme 35) [60, 61]. Free (NH)-indoles and pyrroles react exclusively at the C2, whereas /V-TIPS indole and pyrroles are borylated at the C3 positions. Interestingly, Smith, Maleczka and co-workers also demonstrated that when the C2 position of indole is blocked, then the borylation reaction takes place at the C7-position of the indole nucleus [62]. They propose that an A-chelation to Ir (or B) is responsible for the observed selectivity. 

Another solution is to employ trifluoroborate salts 2.215, which can be prepared from the boronic acid by treatment with potassium hydrogen fluoride (Scheme 2.74). They can also be prepared from alkyl bo-ranes in a similar way (Scheme 2.75). These stable salts can be efficiently employed in Suzuki coupling reactions (Scheme 2.T6)P One application is in the synthesis of the unusual amino acid, trityrosine 2J26 (Scheme 2.77). In this synthesis an aryl diiodide 2.222 was coupled with a trifluoroborate salt 2.224 that had been formed by Miyaura borylation of iodide 2.223 followed by KHF2 treatment. Global debenzylation of coupling product 2.225 gave the product 2.226. Another example of the use of a trifluoroborate salt can be found in Scheme 2.88. 

A variant of these reactions was optimized based on the Hosomi-Miyaura borylation of a,P-unsaturated carbonyl compounds with nucleophilic boryl copper, providing 2-alkoxycarbonyl (as well as 2-acyl- and 2-cyano) allylboronates such as 40 in high stereoselectivity (Equation 22) [60]. The resulting 2-alkoxycarbonyl reagents react with aldehydes to provide a-methylene-y-butyrolactones. 

One of the most active and well-studied catalytic borylation systems is that generated from iridium(l) precursors such as [lr(COD)Cl]2 or [lr(COD)(OMe)]2 and bipyridine type ligands such as 2,2 -bipyridine or 4,4 -di-ferf-butyl-2,2 -bipyridine (dtbpy). In 2002, Ishiyama, Miyaura, and Hartwig et al. reported that the combination of [lr(COD)Cl]2 and 2,2 -bipyridine catalyzes arene borylation in the presence of excess arene under mild conditions (80°C). When the catalyst is generated from [lr(COE)2Cl]2 and dtbpy, the reaction proceeds even at room temperature [78, 79]. The same groups optimized conditions and found that the combination of [Ir(COD) (OMe)]2 and dtbpy (10) is a highly effective catalyst in the borylation of arenes so that reactions can be successfully performed with equimolar ratio of arenes and... 

Although not fitting exactly into the scope of this book, the iridium catalyzed borylation of five membered heterocycles through C-H bond activation also deserves mentioning. A recent report by Miyaura disclosed the reaction of bis(pinacolato)diboron with heteroaromatic systems, where thiophene, fiirane and pyrrole were converted to their 2-boryl derivatives with good selectivity (6.86.), The yields presented refer to the diboron compound since the heterocycles were used in excess in all cases. Indole, benzofurane and benzothiophene were monoborylated with similar efficiency.116... 

Ishiyama, T., Takagi, J., Kamon, A., Miyaura, N. Palladium-catalyzed cross-coupling reaction of bis(pinacolato)diboron with vinyl trifiates -substituted by a carbonyl group efficient synthesis of -boryl- -unsaturated carbonyl compounds and their synthetic utility. J. Organomet. Chem. 2003, 687, 284-290. 

Aryl chlorides typically do not react under these conditions. However, Miyaura has been able to extend the scope of this reaction to include aryl chlorides by changing the catalyst system to Pd(dba)2 and PCys and replacing pinacolborane with bis(pinacolato)diboron. Vinyl iodides and trifiates undergo borylation with pinacolborane under similar conditions in the presence of triphenylarsine (AsPEb) (eq 17). Benzylic halides react with pinacolborane in the presence of PdCl2, PPhs, and N,N-diisopropylethyl amine (eq 18). Borylation of allylic halides in the presence of Pt(dba)2, AsPhs, and EtsN leads to highly regio-and stereoselective allylboronates (eq 19). 

The reactions have been conducted in an excess of the arene to be borylated as the reaction medium [169,170], or in cyclohexane as an inert solvent [168]. For example, Miyaura s group [170] described a rather convenient method for borylation of simple arenes with 350 under mild reaction conditions. Table 10. 

Takagi J, Takahashi K, Ishiyama T, Miyaura N (2002) Palladium-Catalyzed Cross-Coupling Reaction of Bis(pinacolato)diboron with 1-Alkenyl Halides orTriflates Convenient Synthesis of Unsymmetrical 1,3-Dienes via the Borylation-Coupling Sequence. J Am Chem Soc 124 8001... 

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