Catalytic Hydrogenation of Amides to Amines under Mild Conditions

摘要

In 2005, a round table of pharmaceutical companies and the ACS Green Chemistry Institute generated a list of dream reactions that would have an important impact to make the future production of pharmaceuticals more economical, safe and environmentally benign. Among the top candidates in this list was the catalytic hydrogenation of amides to furnish amines, a functional group present in almost any drug or drug candidate. In many cases, the amines are synthesized by the reduction of the corresponding amides, which is typically achieved by using a stoichiometric amount of a hydride reagent such as LiAlH4, DIBAL, RedAl, borane, triethylsi-lane, or polymethylhydroxysilane. Reactions with these reagents suffer from poor atom efficiency and issues regarding both the safety of operation and the removal of stoichiometric metal waste are not uncommon. Conversely, catalytic hydrogenation with molecular hydrogen as reducing agent is ecologically and economically highly attractive with water being the only byproduct (Scheme 1).