Pinacolboronic esters

The palladium(0)-catalyzed borylation/Suzuki coupling protocol was developed by Baudoin and co-workers in order to synthesize sterically hindered 2,2 -disubstituted biaryl compounds such as 170 in high yield and in a convenient manner [162,163], Indeed, the catalytic borylation of 2-bromoaniline 167 (R=H) gave the corresponding pinacolboronic ester 168 which was reacted in a one-pot fashion with phenyl iodide 169 in the presence of barium hydroxide to give the functionalized biphenyl 170 in 78% yield. Cleavage of the MOM group and cyclization in the presence... 

Nevertheless, pinacolboronic esters suffer two disadvantages. First, they are sometimes too stable and thus poorly reactive, especially when compared with boronic reagents of other classes. Second, they derive from pinacol, an expensive compound. 

Aggarwal and coworkers developed an elegant synthesis of tertiary alkyl-boronic esters based on the quenching of an enantiopure lithium derivative, itself issued from the metalation of an enantiopure secondary carbamate (Scheme 3.9). The first successful results were attained with pinacolboronic esters but it was observed that increasing the steric bulk of the reagents... 

This example illustrates that the high stability of pinacolboronic esters, although very convenient for product purification and characterization, can be sometimes deleterious for the reactivity. In such cases, unhindered esters like Bnpg esters are actually better as long as isolation of the ester is not required. Actually, Bhg esters could have been a compromise here however, the reaction in Scheme 3.9 is a 1,2-metalate rearrangement that could in principle be sensitive to chirality on the diol, thus the use of hexylenegly-col (a chiral molecule) is generally not considered (but see Section 3.3.1.2). 

The method is also compatible with pinacol boric ester PrOBpin and was applied to the medium-scale preparation of the pyrazolo[l,5-a]pyri-dine-3-pinacolboronic ester in high yields (a difficult case) (Scheme 3.30). 

The present survey of the reactivity of six-membered, sterically hindered, boronic esters aimed to demonstrate that there are, beyond pinacolboronic esters, other reagents that often exhibit a better stability-reactivity ratio. The comingyears should see a steady shift from ubiquitous pinaeol to a reasoned choice of the best boronic ester for a particular application. 

Reaction conditions Tetrahydrofuran (THF), room temperature Synthetic strategy One-pot synthesis of pinacolboronic esters Catalyst Magnesium (Mg°)... 

Keywords Alkyl/aryl/heteroarylAinyl/allyl bromides, magnesium (Mg), tetrahydrofuran (THF), pinacolborane, room temperature, Grignard cOTiditions/Barbier conditions, pinacolboronic esters... 

Zhong QQ, Ngim KK, Sun M, Li J, Deese A, Chetwyn NP. Strategies for the analysis of highly reactive pinacolboronate esters. J Chromatogr A 2012 1229 216-22. 

The use of alkynyl pinacolboronic esters such as 17 afforded functionalized building blocks with high synthetic potential. The primary boron-functionalized dihydroaromatic intermediate could be used directly in a Suzuki cross-coupling reaction with 2,6-dimethoxyiodobenzene to afford the biphenyl derivative 18 in good yield, which was then converted into heterocycle 19 (Scheme 13.10) [10],... 

In a similar fashion the alkynyl pinacolboronic ester building block 17 could be utilized for the assembly of phenanthrenes and phenanthridines in a comparable reaction sequence [11]. 

A mixture of pinacol ester of diboron (350,280 mg, 1.1 mmol), potassium acetate (300 mg, 3 mmol) and Pd(dppf)Cl2 (3 mol%) was flushed with nitrogen. DMSO (6 ml) and 4-bromoacetophenone (73, 200 mg, 1 mmol) were then added. After being stirred at 80 C for 1 h under nitrogen, the product was extracted with toluene, washed with water and dried over Na2S04. Kugelrohr distillation in vacuo gave 197 mg (80%) of pure 4-acetylphenyl-pinacolboronate (368). 

The photocatalytic generation of aryl radicals was also successfully applied to the formation of carbon heteroatom bonds. The aryl pinacolboronates 141 can be easily achieved by visible light irradiation of a solution of aryl diazonium salts 142 and diboron pinacol ester 143 containing 5mol% of eosin (Scheme 29.24) [89]. The proposed meehanism involves the addition of aryl radical 144 to the complex 145 that is generated by interaction of tetrafluoroborate anion and diboran pinacol ester 143. This process leads to the formation of the aryl pinacolboronates 141 and the radical anion intermediate 146. The oxidation of this intermediate by eosin radical cation completes the catalytic cycle. 

The reactions typically proceed at 150°C with n-octane and di-pinacolboronate for 5-24 h, and the amount of catalyst typically is 1-5%. The yields of 1-octylboronate ester are good and the reaction is regioselective in the terminal alkyl position (second equation below, top of p. 418). The proposed mechanism involves oxidative addition of the B-B or B-H bond, followed by a-bond metathesis between the M-B and R-H bonds, which is driven towards formation of the B-R bond by the Lewis-acid property of boron. Note that 16e species (see Scheme p. 418) could also be involved in oxidative addition of the alkane to give an 18e intermediate M(Bpin)2(H)(R) or M(Bpin)(H)2(R) that would provide R-Bpin as well by reductive elimination. Calculations showed, however, that the o-bond metathesis path is preferred by about 10 kcal mol" over this alkane oxidative-addition path. 

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