Selective Reductions. 29. A Simple Technique To Achieve an Enhanced Rate of Reduction of Representative Organic Compounds by Borane-Dimethyl Sulfide

Article abstract of DOI:10.1021/jo00137a025

A dramatic increase in the rate of reduction of esters by borane-dimethyl sulfide (BMS) is observed when dimethyl sulfide is removed from the reaction mixture.On the basis of this observation, a new, improved procedure has been developed for the reduction by BMS of representative organic functional groups, such as esters, nitriles, and amides.The procedure involves addition of BMS to the substrate in refluxing tetrahydrofuran, allowing the liberated dimethyl sulfide to distill off during the reaction.Stoichiometric studies established the minimum amount of BMS required for the complete reduction of these functional groups.Thus, esters require 2 equiv of hydride (HB<) for the reduction of >C=O to >CH2.Employing this stoichiometry, the reduction of aliphatic esters is quite rapid, complete in 0.5 h, while the reduction of aromatic esters is slower, requiring 4-16 h.The corresponding alcohols are produced in excellent yields.On the other hand, nitriles require 3 equiv of hydride (one borane unit/nitrile) and are reduced rapidly in 0.25 h to the corresponding borazine complex, readily hydrolyzed to the corresponding amines.On the other hand, amides require different equivalents of hydride, depending on the particular type of amide undergoing reduction.Thus, tertiary amides require 5 equiv of hydride and form the amine-borane adducts in 0.25 h.Secondary amides liberate hydrogen prior to forming the amine-borane complex, utilizing 6 equiv of hydride in 0.25-1.0 h.However, primary amides require only 4 equiv of hydride, 2 for hydrogen liberation and 2 for reduction, producing in 1.0-2.0 h the amine dibora derivatives, which are sufficiently weakly basic as not to complex with BMS.The ease of reduction of amides follows the order tertiary<*>secondary>primary.A simple procedure has been described for the reduction of tertiary and secondary amides using decreased amounts of BMS in the presence of boron trifluoride etherate.Unlike lithium aluminum hydride, super hydride, etc., the tendency for C-N bond cleavage to produce the alcohol is completely absent in these reductions of BMS.The reagent permits the presence of many common substituents, such as nitro, chloro, methoxy, etc.The reaction is not significantly susceptible to electronic and steric effects.Simple procedures have been developed for isolating the products.This study establishes a convenient synthetic route for the selective reduction of various organic functional groups with BMS where this transformation is desired in synthetic operations.