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 | Phenylboronic acid | 121.93 | 98-80-6 | 216-219 |
| 2-Thienylboronic acid | Thiophene | 2-thienylboronic acid | 127.96 | 6165-68-0 | 138 -140 |
| Methylboronic acid | Methyl | methylboronic acid | 59.86 | 13061-96-6 | 59.86 |
| cis-Propenylboronic acid | propene | cis-propenylboronic acid | 85.90 | 7547-96-8 | 65-70 |
| trans-Propenylboronic acid | propene | trans-propenylboronic acid | 85.90 | 7547-97-9 | 123-127 |
| Representative boronic acids [1] | |||||
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 [2] by condensation with alcohols and diols. Phenylboronic acid can be selfcondensed to the cyclic trimer called triphenyl anhydride or triphenylboroxin [3]
| Boronic ester | diol | Molar mass | CAS number | Boiling point °C | |
| Allylboronic acid pinacol ester | pinacol | Allylboronic acid pinacol ester or 2-Allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | 168.04 | 72824-04-5 | 50-53°C 5 mm Hg |
| Phenyl boronic acid glycol ester | trimethylene glycol | Phenyl boronic acid glycol ester or 2-Phenyl-1,3,2-dioxaborinane | 161.99 | 4406-77-3 | 106°C 2 mm Hg |
| Diisopropoxymethylborane | isopropanol | Diisopropoxymethylborane | 144.02 | 86595-27-9 | 105 -107°C |
| Representative boronic esters [4] | |||||
Compounds with 6-membered cyclic structures containing the C-O-B-O-C linkage are called dioxaborolanes and those with 5-membered rings dioxaborinanes.
Boronate or borate salts
Boronate salts or borate salts (not encouraged) 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 [5] [6] 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 [7]:
- 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 [8]:
Oxidation
Boronic esters are oxidized to the corresponding alcohols with base and hydrogen peroxide (for an example see: carbenoid)
Homologization
- In boronic ester homologization an alkyl group shifts from boron in a boronate to carbon [9]:
| Boronic ester homologization | Homologization application | |
| 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 a RCH2 group into the C-B bond.
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 [10][11]:
Hydrolysis
Hydrolysis of boronic esters back to the boronic acid and the alcohol can be accomplished in certain systems with thionyl chloride and pyridine [12].
See also
- Boron bonded to three oxygen atoms: boric acid and borates
References
- ↑ www.sigmaaldrich.com
- ↑ Organic Syntheses, Coll. Vol. 5, p.918 (1973); Vol. 49, p.90 (1969). Link
- ↑ Organic Syntheses, Coll. Vol. 4, p.68 (1963); Vol. 39, p.3 (1959). Link
- ↑ www.sigmaaldrich.com
- ↑ Copper promoted C-N and C-O bond cross-coupling with phenyl and pyridylboronatesTetrahedron Letters, Volume 44, Issue 19, 5 May 2003, Pages 3863-3865 Dominic M. T. Chan, Kevin L. Monaco, Renhua Li, Damien Bonne, Charles G. Clark and Patrick Y. S. LamError: Bad DOI specified!
- ↑ Copper-promoted/catalyzed C-N and C-O bond cross-coupling with vinylboronic acid and its utilities Tetrahedron Letters, Volume 44, Issue 26, 23 June 2003, Pages 4927-4931 Patrick Y. S. Lam, Guillaume Vincent, Damien Bonne and Charles G. ClarkError: Bad DOI specified!
- ↑ Catalytic Conjugate Addition of Allyl Groups to Styryl-Activated Enones Joshua D. Sieber, Shubin Liu, and James P. Morken J. Am. Chem. Soc.; 2007; 129(8) pp 2214 - 2215; (Communication) doi:10.1021/ja067878w
- ↑ Benzylic Substitution of Gramines with Boronic Acids and Rhodium or Iridium Catalysts Gabriela de la Herrán, Amaya Segura, and Aurelio G. Csák Org. Lett.; 2007; 9(6) pp 961 - 964; (Letter) doi:10.1021/ol063042m
- ↑ 99% Chirally selective synthesis via pinanediol boronic esters: insect pheromones, diols, and an amino alcohol Donald S. Matteson, Kizhakethil Mathew Sadhu, and Mark L. Peterson J. Am. Chem. Soc.; 1986; 108(4); pp 810 - 819; doi:10.1021/ja00264a039
- ↑ Simple, Stable, and Versatile Double-Allylation Reagents for the Stereoselective Preparation of Skeletally Diverse Compounds Feng Peng and Dennis G. Hall J. Am. Chem. Soc.; 2007; 129(11) pp 3070 - 3071; (Communication) doi:10.1021/ja068985t
- ↑ In this sequence the boronic ester allyl shift is catalyzed by boron trifluoride. In the second step the hydroxyl group is activated as a leaving group by conversion to a triflate by triflic anhydride aided by 2,6-lutidine. The final product is a vinyl cyclopropane. Note: ee stands for enantiomeric excess
- ↑ New asymmetric syntheses with boronic esters and fluoroboranes Donald S. Matteson Pure Appl. Chem., Vol. 75, No. 9, pp. 1249–1253, 2003 Link.