Asymmetric ligands for lanthanide(II) reagents

Abstract

Although the use of Ln(^2+) species as one electron reducing agents has recently become popular, relatively few processes have focused on the control of stereochemistry by the incorporation of chiral auxiliaries at the metal centre. This thesis discusses work aimed at the synthesis of chiral bis(pentaalkylcyclopentadienyl) and polyaza/oxo ligands for Ln(II) ions, and their subsequent application in asymmetric organic synthesis. Synthesis of enantiomerically pure bis(pentaalkylcyclopentadienyl) ligands was attempted via a novel double Nazarov cyclisation of 5,6-di-(methyl)-decane-3,8-dione. A competing intermolecular aldol reaction reduced the efficiency of this route, although subsequent work suggests that the alternative ketone, (3,4-RR/SS)-bis(2'- oxobutyl)tetrahydrofuran, could inhibit aldol formation. In addition, a route for bis(tetramethylcyclopentadienyl) ligands was developed via oxidative coupling of 4-(S)-isopropyl-3-propionyl-oxazolidin-2-one.A range of tetradentate polyaza/oxo ligands have been prepared and their application in enantioselective carbon-carbon bond formation, in particular the Barbier reaction between 2-octanone and bromobutane, investigated. Using N,N'-bis(3'- propionamide)cyclohexane-l,2-diamine, asymmetric induction and a marked acceleration in reaction rate was observed. This represents the first enantioselective Sm(II)-mediated Barbier reaction. The use of aryl ketones affords pinacols with low enantioselectivity.