DABCO bond cleavage for the synthesis of piperazine derivatives

Abstract

The applications of DABCO (1,4-diazabicyclo[2.2.2]octane) in the synthesis of piperazine derivatives including biologically active compounds via C–N bond cleavage are investigated in this review. Different reagents such as alkyl halides, aryl(heteroary) halides, carboxylic acids, diaryliodonium salts, tosyl halides, activated alkynes, benzynes etc. were applied for the preparation of the corresponding quaternary ammonium salts of DABCO, which are very good electrophiles for various nucleophiles such as phenols, thiophenols, thiols, alcohols, aliphatic and aromatic amines, sulfinates, phthalimide, indoles, NaN₃, triazole and terazoles, NaCN, enols and enolates, halides, carboxylic acid salts etc. Besides preactivated DABCO salts, the in situ activation of DABCO in multicomponent reactions is also an efficient tactic in synthetic organic chemistry for the diversity oriented synthesis of drug-like piperazine derivatives.