The combination of group I metal and liquid ammonia is a powerful reducing system capable of reducing alkynes to trans alkenes. In the presence of an alcohol this same combination reduces arenes to non conjugated dienes.
Partial reduction of aromatic rings can be achieved by dissolving metal systems such as sodium, potassium or lithium is liquid ammonia or amine in the presence of alcohol and the reaction is called Brich reduction.
Liquid ammonia serves as solvent. Primary amines can also be used as solvent with advantage because it allows higher temperature of reaction.
MechanismBack to Top
The mechanism of Brich reduction starts with the addition of the electron from the metal to form a resonance stabilized anion radical. This accepts a proton from the alcohol to form a neutral radical. The addition of another electron from the metal to the radical produces an anion which is protonated from a proton of the alcohol to give the dihydro product. The double bonds which become isolated in the dihydro structure are much less readily reduced than the aromatic ring, so the reduction stops at the dihydro stage.
As the repulsion between the anionic and radical centers is minimum, it therefore adds a proton to give the second radical and subsequently a 1,4-dihydro but not 1,2-dihydro product is formed.
RegioselectivityBack to Top
The overall regioselectivity of the Brich reduction has been clear for a long time, the regiochemistry of the individual steps has been studied by means of a conceptual new approach in which two consecutively formed species of differing reactivity exhibit differing kinetic isotopic effects. The zinc reaction of diphenylcyclopropenone can be rationalized in terms of a general mechanism for zinc promoted reductions.
The regioselectivity in Brich reduction is illustrated by the following example.
These examples serve to illustrate a general principle.
- Electron withdrawing groups promote ipso, para Brich reduction.
- Electron donating groups promote ortho, meta Brich reduction.
ApplicationBack to Top
Brich reduction is an important method for reducing heterocyclic aromatic rings. Although Brich reduction of unsubstituted pyrroles tends to give poor yields, reduction of the N-Boc derivatives can give quite good yields, and reduction of pyridine rings to the piperidine derivative has been reported in low yield. Partial reduction of a furan ring is also possible.
As observed in the synthesis of secosyin by Donohoe and co-workers in which reduction led to 68% yield after the reaction of the initially formed anion with the bezylic bromide.