Novel Bispidine-Monoterpene Conjugates-Synthesis and Application as Ligands for the Catalytic Ethylation of Chalcones.

Evgeniy V Suslov,Aldar A Munkuev,Sergey Z Vatsadze,Oxana S Patrusheva,Konstantin Y Ponomarev,Konstantin P Volcho,Alexander I Dalinger,Sergey O Kuranov,Mikhail A Kalinin,Nariman F Salakhutdinov,Roman V Ottenbacher,Alina A Okhina,Artem D Rogachev

doi:10.3390/molecules26247539

Abstract

A number of new chiral bispidines containing monoterpenoid fragments have been obtained. The bispidines were studied as ligands for Ni-catalyzed addition of diethylzinc to chalcones. The conditions for chromatographic analysis by HPLC-UV were developed, in which the peaks of the enantiomers of all synthesized chiral products were separated, which made it possible to determine the enantiomeric excess of the resulting mixture. It was demonstrated that bispidine-monoterpenoid conjugates can be used as the ligands for diethylzinc addition to chalcone C=C double bond but not as inducers of chirality. Besides products of ethylation, formation of products of formal hydrogenation of the chalcone C=C double bond was observed in all cases. Note, that this formation of hydrogenation products in significant amounts in the presence of such catalytic systems was found for the first time. A tentative scheme explaining the formation of all products was proposed.

Highlights

The presence of two spatially close-up nitrogen atoms in the structure of the 3,7diazabicyclo[3.3.1]nonane framework makes bispidines promising bidentate ligands for transition metal complexes [1,2,3]
The possibility of obtaining different bispidine derivatives with substituents at both the carbon scaffold and the nitrogen atoms [4], allows one to vary the rigidity of bispidine core and electronic properties of bispidine complexes, as well as steric accessibility of possible catalytic metal sites of bispidine complexes. This in turn may lead to obtaining catalytic systems with required catalytic properties [5]
It should be noted that the conformational rigidity of the bispidine core determines the volume parameters of coordination space, firstly N . . . N distance

Summary

Introduction

The presence of two spatially close-up nitrogen atoms in the structure of the 3,7diazabicyclo[3.3.1]nonane (bispidine) framework makes bispidines promising bidentate ligands for transition metal complexes [1,2,3]. The possibility of obtaining different bispidine derivatives with substituents at both the carbon scaffold and the nitrogen atoms [4], allows one to vary the rigidity of bispidine core and electronic properties of bispidine complexes, as well as steric accessibility of possible catalytic metal sites of bispidine complexes. This in turn may lead to obtaining catalytic systems with required catalytic properties [5]. This parameter mainly determines the selectivity of complex formation and the stability of the resulting complexes. Complexes of substituted bispidines with transition metals have been investigated in Michael [7] and Henry reactions [8], deprotonation/electrophilic addition [9], oxidative kinetic separation of secondary alcohols [5], hydrogenation of double bonds [5], addition of diethylzinc to aldehydes [5,10] and others

Objectives

Methods

Results