Organoboron reagents

Lewis acidity

A three-coordinate borane is trigonal planar with a vacant p orbital, so it is a Lewis acid. BH_3 is never free in a bottle: it exists as the dimer diborane, B_2H_6, or as adducts such as BH_3·THF and BH_3·SMe_2. Electron-withdrawing groups raise the acidity, so B(C_6F_5)_3 is a strong, air-tolerant Lewis acid, while oxygen substituents in boronic esters donate into the p orbital and tame it.

Hydroboration–oxidation

Borane adds to an alkene through a four-centre transition state in which the B–H bond adds across the C=C in one step. Two outcomes follow.

• Regiochemistry: boron goes to the less substituted carbon (steric and electronic reasons coincide), giving anti-Markovnikov products after oxidation.
• Stereochemistry: H and B add to the same face (syn addition).

Oxidation with alkaline hydrogen peroxide converts C–B to C–OH. Hydroperoxide adds to boron to form a borate, then an alkyl group migrates from boron to the adjacent oxygen, expelling hydroxide. Because the carbon migrates with its electron pair, configuration is retained. Worked example: 1-methylcyclohexene with BH_3·THF and then H_2O_2/NaOH gives trans-2-methylcyclohexan-1-ol, OH and H having been delivered syn to the ring. Hindered boranes such as 9-BBN raise regioselectivity further.

Boronic acids and the Suzuki coupling

Boronic acids are made from aryl Grignard or lithium reagents and trialkyl borates, or by palladium-catalysed Miyaura borylation of aryl halides with B_2pin_2. On standing they partly dehydrate to cyclic boroxines, so pinacol esters (Bpin) are often preferred.

In the Suzuki coupling a Pd(0) catalyst undergoes oxidative addition into Ar–X, then transmetallation transfers the organic group from boron to palladium, then reductive elimination forms the new C–C bond and regenerates Pd(0). Base is essential: it converts the boronic acid into an anionic tetrahedral boronate, or the palladium halide into a Pd–OH species, and either route speeds transmetallation. For example, 4-bromoanisole and phenylboronic acid with Pd(PPh_3)_4 and K_2CO_3 in aqueous dioxane give 4-methoxybiphenyl. Boron by-products are non-toxic and water-soluble, a big reason industry favours this reaction.

Frustrated Lewis pairs

If a Lewis acid and base are too bulky to form an adduct, their reactivity stays 'unquenched'. A bulky phosphine with B(C_6F_5)_3 splits H_2 heterolytically into a phosphonium cation and a hydridoborate anion, and such pairs catalyse metal-free hydrogenation of imines.

Organoboron chemistry is now as much about building stereocentres and complex scaffolds as about Suzuki couplings.

C–H borylation. Iridium catalysts with bipyridine ligands and B_2pin_2 borylate arenes under steric control, typically at the least hindered position, which often means meta to an existing substituent. Directed and ligand-controlled variants now reach ortho, para and even C(sp^3)–H positions, turning C–H bonds into handles for later coupling.

Stable, slow-release reagents. Many 2-heteroaryl boronic acids lose boron to protodeboronation faster than they couple. MIDA boronates, with boron locked in a tetrahedral cage, survive chromatography and only release the boronic acid under aqueous base; this allows iterative cross-coupling, where one building block is coupled while another boron site stays masked. Potassium organotrifluoroborates serve a similar role.

Stereospecific chemistry. The 1,2-metallate rearrangement of boronate complexes underlies Matteson homologation and lithiation–borylation, which add one carbon at a time with control over each new stereocentre and allow 'assembly-line' synthesis of chains with many contiguous stereocentres. Because C–B bonds can then be converted into C–O, C–N or C–C bonds with retention, a single chiral boronic ester is a branch point to many products.

Medicine. Bortezomib and ixazomib inhibit the proteasome by forming a reversible covalent bond between boron and a threonine hydroxyl; vaborbactam inhibits β-lactamases, and the benzoxaboroles tavaborole and crisaborole treat fungal nail infection and eczema.

Frustrated Lewis pairs have moved from H_2 splitting to catalytic hydrogenation, CO_2 capture and reduction, and borylation of heteroarenes. Open questions include tolerance of water and functional groups, which still limits FLP catalysis in industry, and how much of FLP reactivity proceeds through single-electron transfer rather than the classical two-electron picture.