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-Aromatic compounds are reduced to 1,4-cyclohexadienes by treatment with alkali matals (Li, Na, or K) or alkaline earth metals (Ca or Mg) dissolved in a mixed solvent of liquid ammonia and alcohol.
-α,β-Unsaturated carbonyl compounds, conjugated dienes, and alkynes are also reduced. The Birch reduction of alkynes give E-olefins selectively. The Birch conditions are also used for the deprotection of benzyl and arylsulfonyl groups.
-Conditions such as Li/DBB (4,4’-di-t-butylbiphenyl) and Na/naphthalene are known as milder alternatives. These conditions are more functional group tolerant than the original Birch conditions.
-Low molecular weight alkyl amines can be used instead of liquid ammonia, in which case the amine serves as a proton source. The reactions can be run at higher temperatures and provide a more strongly reducing system (the Benkeser reduction).
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・ Benkeser, R. A.; Robinson, R. E.; Landesman, H. J. Am. Chem. Soc. 1952, 74, 5699. DOI: 10.1021/ja01142a041
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・ Benkeser, R. A.; Belmonte, F. G.; Kang, J. J. Org. Chem. 1983, 48, 2796. DOI: 10.1021/jo00165a003
・Watt, G. W. Chem. Rev. 1950, 46, 317. DOI: 10.1021/cr60144a003
・Birch, A.J. Quart. Rev. 1950, 4, 69.
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・Kaiser, E. M. Synthesis 1972, 391. DOI: 10.1055/s-1972-21889
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・Zimmerman, H. E. Acc. Chem. Res. 2012, 45, 164. DOI: 10.1021/ar2000698
The regioselectivity of the Birch reduction is determined by the stability of the anionic intermediates. When the substituent is electron-withdrawing, the anion at the ipso position is stabilized, while the opposite is true when the substituent is electron-donating. (ref: J. Am. Chem. Soc. 1993, 115, 2205., Acc. Chem. Res. 2012, 45, 164.)
The addition of alcohols as a cosolvent helps in preventing undesired isomerizations caused by the strongly basic NH2– anion.
The relative rate for the reduction of benzene is Li(360) > Na(2) > K(1).
The carbanion stabilized by the electron withdrawing groups can be trapped with electrophiles to form carbon-carbon bonds. An example is shown.
The Birch reduction of pyrroles.
-Ammonia boils at about -33˚C. Use a Dewar condenser instead of a regular condenser.
-Teflon-coated stirring bars get corroded and turn black under the Birch conditions. It is better to use glass-coated stirrers.
-Lithium wire is rinsed with pentane to remove the oil first, and then cut by scissors to small pieces.
-The “active” reaction mixture should be colored deep blue.
-Isoprene is sometimes used to quench these one-electron reduction reactions.