The best reagent for this is borane, BH₃. Borane is, in fact, a gas with the structure B₂H₆, but it can be ‘tamed’ as a liquid by complexing it with ether (Et₂O), THF, or dimethyl sulfide (DMS, Me₂S). Although borane appears superficially similar to borohydride, it is not charged, and that makes all the difference to its reactivity. Whereas borohydride reacts best with the most electro philic carbonyl groups, borane’s reactivity is dominated by its desire to accept an electron pair into the boron’s empty p orbital. In the context of carbonyl group reductions, this means that borane reduces electron-rich carbonyl groups fastest. The carbonyl groups of acyl chlorides and esters are relatively electron-poor (Cl and OR are very electronegative); borane will not touch acyl chlorides and reduces esters only slowly. But it will reduce very effectively both carboxylic acids and amides. Borane reacts with carboxylic acids fi rst of all to form triacylborates, with evolution of hydrogen gas. Esters are usually less electrophilic than ketones because of conjugation between the carbonyl group and the lone pair of the sp3 hybridized oxygen atom—but, in these boron esters, the oxygen next to the boron has to share its lone pair between the carbonyl group and the boron’s empty p orbital, so they are considerably more reactive than normal esters.

Borane is a highly chemoselective reagent for the reduction of carboxylic acids in the presence of other reducible functional groups such as esters, and even ketones.

Borane and lithium borohydride are a most useful pair of reducing agents, with opposite selectivities. Japanese chemists used an enzyme to make a single enantiomer of the acid below, and were able to reduce either the ester or the carboxylic acid by choosing lithium borohydride or borane as their reagent. Check for yourself that the lactones (cyclic esters) in black frames are enantiomers.

Because borane reacts well with electron-rich carbonyl groups, it is also a good alternative to LiAlH₄ for reducing amides to amines, and is chemoselective even in the presence of an ester:

The carbonyl group of an amide is electron-rich because it receives electron density from the delocalized N lone pair. It therefore complexes well with the empty p orbital of the Lewis acidic borane. Hydride transfer is then possible from anionic boron to electrophilic carbon. The resulting tetrahedral intermediate collapses to an iminium ion that is reduced again by the borane.

مواضيع ذات صلة

How to reduce amides to amines

The benzyne mechanism

Other nucleophiles

The SN1 mechanism for nucleophilic aromatic substitution: diazonium compounds

The activating anion-stabilizing substituent

The leaving group and the mechanism

The intermediate in the addition–elimination mechanism

The addition–elimination mechanism

Nucleophilic aromatic substitution

Nucleophilic epoxidation

Conjugate substitution reactions

Unsaturated nitriles and nitro compounds