Short Synthesis of Enantiopure trans-3-Arylpiperazine-2-carboxylic Acid Derivatives via Diaza-Cope Rearrangement

Abstract

An efficient synthetic method was developed for the construction of enantiomerically pure trans-3-arylpiperazine-2-carboxylic acid derivatives using diaza-Cope rearrangement (DCR) as a key step starting from (R,R)/(S,S)-1,2-bis(2-hydroxyphenyl)-1,2-diaminoethane (HPEN). A complete transfer of stereochemical integrity was observed for the transformation. Piperazine ring formation from the chiral 1,2-ethylenediamine derivatives using diphenylvinylsulfonium triflate followed by oxidation using ruthenium(III) chloride monohydrate in the presence of sodium periodate provided the desired enantiopure trans-3-arylpiperazine-2-carboxylic acid derivatives.

Resonance‐Assisted Hydrogen Bonding as a Driving Force in Synthesis and a Synthon in the Design of Materials

“…RAHB-assisted regioselective CÀCc leavage in (E/Z)-2-[2-(4-substitutedphenyl)hydrazono]-4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3dione. [109,110,[273][274][275][276][277][278][279][280] DCR allows the preparationc hiral vicinal diamines including C 2 symmetric diaryl and dialkyl diamines, as well as unsymmetrical alkyl-aryl and aryl-aryld iamines with excellent yields and enantiopurities. Eur.J.…”

“…Eur.J. [273][274][275][276][277][278][279][280] The rearranged diimine is then hydrolyzed to give the target product diamine (referreda st he "daughter" diamine).…”

“…The diaza‐Cope rearrangement (DCR; Scheme , route II) was first used in 1976 by Vögtle and Goldschmitt to prepare a variety of chiral diamines (routes I–III in Scheme ), which is an extensively studied organic reaction with considerable synthetic and mechanistic interest . Thus, treatment of 1,2‐bis(2‐hydroxyphenyl)‐1,2‐diaminoethane (referred as the “mother” diamine) with two equivalents of an aromatic aldehyde results in the formation of the corresponding diimine, which undergoes the DCR reaction to give the rearranged diimine supported by RAHB.…”

“…The rearranged diimine is then hydrolyzed to give the target product diamine (referred as the “daughter” diamine) . RAHB‐directed DCR has given rise to an immense variety of chiral diamines derived from various diamines and aldehydes including heterocyclic aldehydes as starting materials …”

“…DCR allows the preparation chiral vicinal diamines including C 2 symmetric diaryl and dialkyl diamines, as well as unsymmetrical alkyl‐aryl and aryl‐aryl diamines with excellent yields and enantiopurities . Weak forces such as hydrogen bonding, electronic, steric and oxyanion factors affecting kinetics and thermodynamics of the DCR were systematically studied by combining computational and experimental approaches …”