Rapid and Selective Reduction of Functionalized Aromatic Disulfides with Lithium Tri-tert-butoxyaluminohydride. A Remarkable Steric and Electronic Control. Comparison of Various Hydride Reagents

Article abstract of DOI:10.1021/jo00279a041

Lithium tri-tert-butoxyaluminohydride (LTBA), an exceptionally mild reducing agent in organic synthesis, reduces functionalized aromatic disulfides to the corresponding thiols in quantitative yield.The reaction is rapid (for example, o-tolyl disulfide is reduced to completion in 60 min at 25 deg C) and can tolerate a wide variety of functional groups, such as halogen, nitro, carboxylic acid, and their derivatives.The presence of electron-withdrawing substituents dramatically enhances the rate of reduction (p-chlorophenyl disulfide is quantitatively reduced in 30 s) and electron-releasing substituents diminishes the rate of cleavage.The reaction is sensitive to steric effects (2,4-di-tert-pentylphenyl disulfide underwent 25percent reduction in 24 h).However, such hindered disulfides can be rapidly and quantitatively reduced in refluxing THF.The reaction of LTBA with alkyl disulfides is extremely sluggish.The reaction provides a useful and simple means for the facile and selective reduction of aromatic disulfides where this is required in synthetic operations.