Definitions

boronic

Boronic acid


A boronic acid is an alkyl or aryl substituted boric acid containing a carbon to boron chemical bond belonging to the larger class of organoboranes. Boronic acids act as Lewis acids. Their unique feature are that they are capable of forming reversible covalent complexes with sugars, amino acids, hydroxamic acids, etc. (molecules with vicinal, (1,2) or occasionally (1,3) substituted Lewis base donors (alcohol, amine, carboxylate). The pKa of a boronic acid is ~9, but upon complexion in aqueous solutions, they form tetrahedral boronate complexes with pKa ~7. They are occasionally used in the area of molecular recognition to bind to saccharides for fluorescent detection or selective transport of saccharides across membranes.

Boronic acids are used extensively in organic chemistry as chemical building blocks and intermediates predominantly in the Suzuki coupling. A key concept in its chemistry is transmetallation of its organic residue to a transition metal.

The compound bortezomib with a boronic acid group is a drug used in Chemotherapy. The boron atom in this molecule is a key substructure because through it certain proteasomes are blocked that would otherwise degrade proteins

Boronic acids

Many air-stable boronic acids are commercially available. They are characterised by high melting points.

Boronic acid R Molar mass CAS number Melting point °C
Phenylboronic acid Phenyl 121.93 98-80-6 216-219
2-Thienylboronic acid Thiophene 127.96 6165-68-0 138 -140
Methylboronic acid Methyl 59.86 13061-96-6 59.86
cis-Propenylboronic acid propene 85.90 7547-96-8 65-70
trans-Propenylboronic acid propene 85.90 7547-97-9 123-127
Representative boronic acids

Borinic acids and esters

Borinic acids and borinic esters have the general structure R2BOR.

compound general formula general structure
boronic acid RB(OH)2
boronic ester
(boronate ester)
RB(OR)2
borinic acid R2BOH
borinic ester
(borinate ester)
R2BOR

Boronic esters

When hydrogen is replaced by any organic residue the resulting compound is called a boronic ester or boronate ester. The compounds can be obtained from boric esters by condensation with alcohols and diols. Phenylboronic acid can be selfcondensed to the cyclic trimer called triphenyl anhydride or triphenylboroxin

Boronic ester diol Molar mass CAS number Boiling point °C
Allylboronic acid pinacol ester pinacol 168.04 72824-04-5 50-53°C 5 mm Hg
Phenyl boronic acid glycol ester trimethylene glycol 161.99 4406-77-3 106°C 2 mm Hg
Diisopropoxymethylborane isopropanol 144.02

86595-27-9 105 -107°C
Representative boronic esters

Compounds with 5-membered cyclic structures containing the C-O-B-O-C linkage are called dioxaborolanes and those with 6-membered rings dioxaborinanes.

Boronate or borate salts

Boronate salts or borate salts (not encouraged) are ate complexes and have the general structure R4B-M+ for example potassium tetraphenylborate.

Boronic acids in organic chemistry

Suzuki coupling reaction

Boronic acids are used in organic chemistry in the Suzuki reaction. In this reaction the boron atom exchanges its aryl group with an alkoxy group from palladium.

Chan-Lam coupling

In the Chan-Lam coupling the alkyl, alkenyl or aryl boronic acid reacts with a N-H or O-H containing compound with Cu(II) such as copper(II) acetate and oxygen and a base such as pyridine forming a new carbon-nitrogen bond or carbon-oxygen bond for example in this reaction of 2-pyridone with trans-1-hexenylboronic acid:

The reaction mechanism sequence is deprotonation of the amine, coordination of the amine to the copper(II), transmetallation (transferring the alkyl boron group to copper and the copper acetate group to boron), oxidation of Cu(II) to Cu(III) by oxygen and finally reductive elimination of Cu(III) to Cu(I) with formation of the product. Direct reductive elimination of Cu(II) to Cu(0) also takes place but is very slow. In catalytic systems oxygen also regenerates the Cu(II) catalyst.

Conjugate addition

The boronic acid organic residue is a nucleophile in conjugate addition also in conjunction with a metal. In one study the pinacol ester of allylboronic acid is reacted with dibenzylidene acetone in a such a conjugate addition :

The catalyst system in this reaction is tris(dibenzylideneacetone)dipalladium(0) / tricyclohexylphosphine.

Another conjugate addition is that of gramine with phenylboronic acid catalyzed by cyclooctadiene rhodium chloride dimer :

Oxidation

Boronic esters are oxidized to the corresponding alcohols with base and hydrogen peroxide (for an example see: carbenoid)

Homologization

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Boronic ester homologization mechanism Homologization application

In this reaction dichloromethyllithium converts the boronic ester into a boronate. A lewis acid then induces a rearrangement of the alkyl group with displacement of the chlorine group. Finally an organometallic reagent such as a Grignard reagent displaces the second chlorine atom effectively leading to insertion of an RCH2 group into the C-B bond. Another reaction featuring a boronate alkyl migration is the Petasis reaction.

Electrophilic allyl shifts

Allyl boronic esters engage in electrophilic allyl shifts very much like silicon pendant in the Sakurai reaction. In one study a diallylation reagent combines both :

Hydrolysis

Hydrolysis of boronic esters back to the boronic acid and the alcohol can be accomplished in certain systems with thionyl chloride and pyridine .

C-H coupling reactions

The diboron compound bis(pinacolato)diboron reacts with aromatic heterocycles or simple arenes to an arylboronate ester with iridium catalyst [IrCl(COD)]2 (a modification of Crabtree's catalyst) and base 4,4′-di-tert-butyl-2,2′-bipyridine in a C-H coupling reaction for example with benzene:

In one modification the arene reacts 1 on 1 (instead of a large excess) with cheaper pinacolborane

Unlike in ordinary electrophilic aromatic substitution (EAS) where electronic effects dominate, the regioselectivity in this reaction type is solely determined by the steric bulk of the iridium complex. This is exploited in a meta-bromination of m-xylene which by standard AES would give the ortho product :

Boronic acids in supramolecular chemistry

Saccharide recognition

The covalent pair-wise interaction between boronic acids and 1,2- or 1,3-diols in aqueous systems is rapid and reversible. As such the equilibrium established between boronic acids and the hydroxyl groups present on saccharides has been successfully employed to develop a range of sensors for saccharides. One of the key advantages with this dynamic covalent strategy lies in the ability of boronic acids to overcome the challenge of binding neutral species in aqueous media. If arranged correctly, the introduction of a tertiary amine within these supramolecular systems will permit binding to occur at physiological pH and allow signalling mechanisms such as photoinduced electron transfer mediated fluorescence emission to report the binding event.

Potential applications for this research include systems to monitor diabetic blood glucose levels. As the sensors employ an optical response, monitoring could be achieved using minimally invasive methods, one such example is the investigation of a contact lens doped with boronic acid based senors to monitor glucose levels within ocular fluid.

References

See also

External links

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