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 acid||R||Molar mass||CAS number||Melting point °C|
|2-Thienylboronic acid||Thiophene||127.96||6165-68-0||138 -140|
|Representative boronic acids|
|compound||general formula||general structure|
|boronic acid||RB(OH)2|| |
|borinic acid||R2BOH|| |
|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|
|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.
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.
|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.
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 :
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.