Methods for the Synthesis of Piperazine Derivatives Containing a Chiral Bi-2-naphthyl Moiety

Abstract

Piperazine derivatives containing 1,1′-bi-2-naphthyl moiety were synthesized starting from 2,2′-dimethoxy-1,1′-bi-naphthalene via acylation using ethyl chlorooxoacetate and subsequent condensation with 1,2-diamines followed by reduction of the corresponding dihydro-2-piperazinone intermediate using the NaBH 4 /I 2 reagent system. The corresponding chiral piperazine derivatives containing bi-2-napthyl moiety was synthesized by asymmetric reduction of ethyl dimethoxy-bi-2-naphthyloxoacetate by chiral oxazoborolidine catalyst prepared in situ using S -diphenylprolinol (S -DPP), B(OCH 3) 3 and H 3 B·THF. The resulting diols were mesylated and cyclized using 1,2-diamines to obtain the corresponding chiral piperazine derivatives.