Recent developments in the synthesis of piperazines (microreview)

Iridium-Catalyzed Regio- and Diastereoselective Synthesis of C-Substituted Piperazines

“…The piperazine ring is a key pharmacophore for a wide range of drugs, including those with antibiotic, antidepressant, anti-HIV, anticancer, antiviral, antimicrobial, and anxiolytic activities (some examples are shown in Figure ). Considerable efforts have been devoted to the development of synthetic routes yielding this privileged drug scaffold, which have traditionally focused on the reduction of diketopiperazines, the reductive amination of dicarbonyl compounds, and transition-metal-catalyzed cyclization reactions . These methods often require multistep synthesis, as well as protecting and deprotecting steps .…”

“… 1 Considerable efforts have been devoted to the development of synthetic routes yielding this privileged drug scaffold, which have traditionally focused on the reduction of diketopiperazines, the reductive amination of dicarbonyl compounds, and transition-metal-catalyzed cyclization reactions. 2 These methods often require multistep synthesis, as well as protecting and deprotecting steps. 3 More sustainable approaches include a “borrowing hydrogen” method, which uses 1,5-diols and primary amines, the synthesis of 2-substituted piperazines by an iridium photocatalyst, 4 and biocatalytic reductive aminations of 1,2-dicarbonyl and 1,2-diamine substrates, which yield piperazines in an atom-economical fashion.…”