Selective reduction with lithium trialkylaluminumhydrides

Abstract

Lithium diisobutyl-n-butylaluminum hydride, the "ate" complex generated from diisobutylaluminum hydride and n-butyllithium in an equimolar ratio, was reacted with a series of selected organic compounds containing various functional groups in order to explore the reducing properties and to determine the synthetic utility of the reagent. The reagent exhibits excellent stereoselectivties in the reduction of sterically hindered cyclohexanones and bicyclic ketones to give thermodynamically less stable alcohols. The reagent was very effective for selective 1,2-reduction of both acyclic and cyclic enones. The reagent rapidly reduces simple primary alkyl, benzyl, and allyl bromides but slowly primary alkyl chlorides and secondary alkyl bromides. Tertiary alkyl and aryl halides are essentially inert to the reagent. Esters and lactones are completely reduced to the corresponding alcohols at room temperature, whereas they are reduced to the corresponding alcohols and aldehydes at -78$^\circ$C even with an excess amount of the reagent. Acid chlorides and acid anhydrides are rapidly reduced to the corresponding alcohols and an equimolar mixture of the acid and the alcohol at -78$^\circ$C, respectively. Carboxylic acids and primary and secondary amides are inert to the reagent at room temperature. Tertiary amides are cleanly reduced to the aldehydes with a stoichiometric amount of the reagent either at 0$^\circ$ or at room temperature, whereas they are inert to the reagent at -78$^\circ$C. Epoxides are cleanly reduced to the corresponding alcohols in excellent isomeric purity. Nitriles are resistant to reduction and are only slowly converted to the corresponding aldehydes at room temperature. Disulfides are rapidly reduced to the corresponding thiols. Sulfoxides and sulfones are inert to the reagent. Selective reduction of an ester in the presence of a bromide, a tertiary amide, and a nitrile are achieved with the reagent at -78$^\circ$C by using a modified procedure. Furthe...