Synthesis of novel chiral bidentatephosphite ligands derived from the pyranoside backbone of monosaccharides and their application in the Cu-catalyzed conjugate addition of dialkylzinc to enones

Abstract

A series of novel bidentatephosphite ligands, derived from methyl 3,6-anhydro-α- d-glucopyranoside and chlorophosphoric acid diaryl ester, were easily synthesized. These ligands were successfully employed in the Cu-catalyzed asymmetric conjugate 1,4-addition of the organozinc reagents diethylzinc and/or dimethylzinc to enones. The stereochemically matched combination of glucopyranoside and ( R)-H 8-binaphthyl in ligand 2,4-bis{[( R)-1,1′-H 8-binaphthyl-2,2′-diyl] phosphite}-methyl 3,6-anhydro-α- d-glucopyranoside was essential to afford 85% ee for 3-ethylcyclohexanone with an ( S)-configuration in THF, using Cu(OTf) 2 as a catalytic precursor. When the reaction was carried out at lower temperatures, changing from −10 to −80 °C, a marginal influence of the temperature on the enantioselectivity of the reaction was observed. The presence of the methyl substituent at the 1-position of the glucopyranoside skeleton had a negative effect on the enantioselectivity in the 1,4-addition of ZnEt 2 to acyclic enones.